PMID:  Children (Basel). 2023 Feb 27 ;10(3). Epub 2023 Feb 27. PMID: 36980026 Abstract Title:  Vitamin D and Omega-3 (Fatty Acid) Supplementation in Pregnancy for the Primary Prevention of Food Allergy in Children-Literature Review. Abstract:  During the last decades the prevalence of food allergy (FA), an adverse immune response to a specific food antigen, has risen, with negative effects on the quality of life (QoL) of many children and their families. The pathogenesis of FA is complex, involving both genetic and environmental factors. SPINK5, STAT6, HLA and FOXP3 are some of the genes that are reported to be implicated in FA development. Regarding environmental factors, particular interest has been focused on modification of the dietary habits of pregnant women for the primary prevention of FA. Specifically, Vitamin D and omega-3 (-3) fatty acid supplementation during pregnancy may influence the development of FA in the offspring. Vitamin D is a hormone with various actions, including mediation of the immune system, reducing the production of inflammatory cytokines and promoting tolerance. Vitamin D deficiency in pregnancy suppresses T-regulatory cells in the fetus, and Vitamin D supplementation might protect against FA development. Dietary-3 fatty acids are found mainly in fish and vegetable oils. They are beneficial for human health, playing a role in the immune system as anti-inflammatory agents, and providing cell membrane stabilization with inhibition of antigen presentation. It is documented that maternal supplementation with-3 during pregnancy may protect from allergic sensitization in the children. The aim of this literature review was to explore the potential preventive role of maternal supplementation during pregnancy with Vitamin D and-3 in the development of FA in the offspring. With the prevalence of FA rising, all the possible protective mechanisms and measures for FA prevention need to be explored, starting with those that can be modified.

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PMID:  Int J Biol Macromol. 2023 Jun 1 ;239:124201. Epub 2023 Mar 30. PMID: 37001771 Abstract Title:  Investigation of the antitumor effect on breast cancer cells of the electrospun amygdalin-loaded poly(l-lactic acid)/poly(ethylene glycol) nanofibers. Abstract:  In this study, PLA/PEG nanofibers (NFs) loaded with amygdalin (AMG) and bitter almond kernels extract were produced by electrospinning to prevent local breast cancer recurrence, and the effect of produced NFs on the MCF-7 cell line was investigated in vitro. The electrospun NFs were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis (DSC) and tensile strength and physical analyzes were performed. Loading of AMG to nanofibers increased fiber diameters from 827.93  174.507 nm to 1855.32  291.057 m. When drug release results were analyzed, the NFs showed a controlled release profile extending up to 10 h. The encapsulation efficiency of AMG-loaded NFs was calculated at 100  0,01 %, 94  0,02 %, and 88  0,02 %. When in vitro cytotoxicity results were analyzed, showed that all NFs are effective in inducing cytotoxicity against MCF-7 breast cancer cells. Importantly, 20 mg AMG-loaded NFs displayed effectively higher cytotoxic effects against breast cancer cells relative to the other NFs. Considering all the results, AMG-loaded NFs can give sustained release of drugs at the local sites. Therefore, AMG-loaded nanofibers can reduce the risk of local recurrence of cancer after surgery and can be directly implanted into solid tumor cells for treatment.

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PMID:  Int Wound J. 2023 Apr 28. Epub 2023 Apr 28. PMID: 37118938 Abstract Title:  Effects of vitamin C combined with rbFGF on inflammatory factors and oxygen environment in patients with high-voltage electrical burns. Abstract:  To investigate the effect of vitamin C combined with recombinant basic fibroblast growth factor (rbFGF) on inflammatory factors and oxygen environment in patients with high-voltage electrical burns. A retrospective analysis of 98 patients with high-voltage electrical burns admitted to our hospital from January 2021 to April 2022. A total of 98 patients were divided into research group and control group, including 49 cases treated with vitamin C combined with rbFGF and 49 cases treated with only rbFGF. The disappearance time of clinical symptoms, wound healing rate, area of granulation tissue growth, level of inflammatory factors, oxygen environment were compared between two groups after one and three courses of treatment. After treatment, the disappearance time of erythema, pain, swelling, blisters, exudate symptoms, wound healing time, scab formation time, and hospitalisation time in the research group were significantly better than those in control group (P.05), while it is significantly better than those in control group after three courses of treatment (P

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PMID:  Antioxidants (Basel). 2023 Apr 17 ;12(4). Epub 2023 Apr 17. PMID: 37107316 Abstract Title:  Inflammation and Vitamin C in Women with Prenatal Depression and Anxiety: Effect of Multinutrient Supplementation. Abstract:  Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (= 0.007) but did not affect the inflammatory biomarker concentrations (>0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes.

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PMID:  Front Pharmacol. 2023 ;14:1163694. Epub 2023 Apr 5. PMID: 37089915 Abstract Title:  Vitamin C and vitamin Dalleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolismthe gut-liver axis. Abstract:  Previous studies have demonstrated that both vitamin C (VC) and vitamin D(VDhave therapeutic potential against metabolic disorders, including obesity, diabetes, and metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether VC supplementation is associated with improving the intestinal flora and regulating the metabolism of bile acidsthe gut-liver axis in MAFLD. There is still no direct comparison or combination study of these two vitamins on these effects.In this study, we employed biochemical, histological, 16S rDNA-based microbiological, non-targeted liver metabolomic, and quantitative real-time polymerase chain reaction analyses to explore the intervening effect and mechanism of VC and VDon MAFLD by using a high-fat diet (HFD)-induced obese mouse model.Treatment of mice with VC and VDefficiently reversed the characteristics of MAFLD, such as obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation. VC and VDshowed similar beneficial effects as mentioned above in HFD-induced obese mice. Interestingly, VC and VDreshaped the gut microbiota composition; improved gut barrier integrity; ameliorated oxidative stress and inflammation in the gut-liver axis; inhibited bile acid salt reflux-related ASBT; activated bile acid synthesis-related CYP7A1, bile acid receptor FXR, and bile acid transportation-related BSEP in the gut-liver axis; and improved bile secretion, thus decreasing the expression of FAS in the liver and efficiently ameliorating MAFLD in mice.Together, the results indicate that the anti-MAFLD activities of VC and VDare linked to improved gut-liver interactionsregulation of the gut microbiota and bile acid metabolism, and they may therefore prove useful in treating MAFLD clinically.

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PMID:  Front Nutr. 2023 ;10:1094757. Epub 2023 Mar 24. PMID: 37051117 Abstract Title:  Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis. Abstract:  BACKGROUND: This meta-analysis aimed at investigating the pooled evidence regarding the effects of intravenous vitamin C (IVVC) on mortality rate in critically ill patients.METHODS: Databases including Medline, Embase, and Cochrane Library were searched from inception to October, 2022 to identify RCTs. The primary outcome was the risk of overall mortality. Subgroup analyses were performed based on IVVC dosage (i.e., cut-off value: 100 mg/kg/day or 10000 mg/day). Trial sequential analysis (TSA) was used to examine the robustness of evidence.RESULTS: A total of 12 trials including 1,712 patients were analyzed. Although meta-analysis demonstrated a lower risk of mortality in patients with IVVC treatment compared to those without [risk ratio (RR): 0.76, 95% CI: 0.6 to 0.97,= 0.02,= 36%, 1,711 patients), TSA suggested the need for more studies for verification. Moreover, subgroup analyses revealed a reduced mortality risk associated with a low IVVC dosage (RR = 0.72,= 0.03, 546 patients), while no beneficial effect was noted with high IVVC dosage (RR = 0.74,= 0.13,= 60%, 1,165 patients). The durations of vasopressor [mean difference (MD): -37.75 h, 404 patients) and mechanical ventilation (MD: -47.29 h, 388 patients) use were shorter in the IVVC group than those in the controls, while there was no significant difference in other prognostic outcomes (e.g., length of stay in intensive care unit/hospital) between the two groups.CONCLUSION: Although intravenous vitamin C as a monotherapy reduced pooled mortality, durations of vasopressor use and mechanical ventilation, further research is required to support our findings and to identify the optimal dosage of vitamin C in the critical care setting.SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42022371090.

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PMID:  Nutrients. 2023 Apr 19 ;15(8). Epub 2023 Apr 19. PMID: 37111190 Abstract Title:  The Role of a Ketogenic Diet in the Treatment of Dementia in Type 2 Diabetes Mellitus. Abstract:  Type 2 diabetes mellitus (T2DM) shares a common molecular mechanism and underlying pathology with dementia, and studies indicate that dementia is widespread in people with T2DM. Currently, T2DM-induced cognitive impairment is characterized by altered insulin and cerebral glucose metabolism, leading to a shorter life span. Increasing evidence indicates that nutritional and metabolic treatments can possibly alleviate these issues, as there is a lack of efficient preventative and treatment methods. The ketogenic diet (KD) is a very high-fat, low-carbohydrate diet that induces ketosis in the body by producing a fasting-like effect, and neurons in the aged brain are protected from damage by ketone bodies. Moreover, the creation of ketone bodies may improve brain neuronal function, decrease inflammatory expression and reactive oxygen species (ROS) production, and restore neuronal metabolism. As a result, the KD has drawn attention as a potential treatment for neurological diseases, such as T2DM-induced dementia. This review aims to examine the role of the KD in the prevention of dementia risk in T2DM patients and to outline specific aspects of the neuroprotective effects of the KD, providing a rationale for the implementation of dietary interventions as a therapeutic strategy for T2DM-induced dementia in the future.

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PMID:  Psychiatr Pol. 2022 Dec 31 ;56(6):1345-1363. Epub 2022 Dec 31. PMID: 37098202 Abstract Title:  Ketogenic diet in therapy of bipolar affective disorder - case report and literature review. Abstract:  Bipolar affective disorder (BPAD) is a chronic mental disorder, characterised by mood swings, alternating between depression and manic or hypomanic episodes. Unfortunately, in some patients pharmacological treatment does not bring satisfactory results, and a certain group of patients shows resistance to treatment. Therefore, other treatment methods are sought after, including a change in diet. The most promising nutrition model is the ketogenic diet. In the presented case study of a male patient, thanks to the introduction of the ketogenic diet, full remission of the disease was achieved, doses of lamotrigine were reduced and quetiapine was completely discontinued. Previously, neither lamotrigine monotherapy nor combined treatment with quetiapine achieved euthymia. The effects of the diet may be related to, among others, the influence on ionic channels and increase in blood acidity (similarly to mood stabilisers), increase in gamma-aminobutyric acid (GABA) concentration, modulation of GABAA receptors and blocking of AMPA receptors by medium-chain fatty acids. The ketogenic diet influences glutamate metabolism and nerve cell metabolism, which uses ketone bodies as energy sources. Ketosis can also stimulate the biogenesis of mitochondria, improve brain metabolism, act as a neuroprotective factor, as well as increase glutathione synthesis and reduce oxidative stress. However, there is a need for carefully planned studies, with an appropriate representative group, to verify the potential benefits and risks of introducing the ketogenic diet in patients with BPAD.

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PMID:  Nutrition. 2023 Jun ;110:111976. Epub 2023 Feb 12. PMID: 37060636 Abstract Title:  The ketogenic diet for Dravet syndrome: A multicenter retrospective study. Abstract:  OBJECTIVE: The ketogenic diet (KD) is one of the main treatments for drug-resistant epilepsy. However, there have been few multicenter reports on the use of the KD for the treatment of Dravet syndrome (DS). The aim of this study was to analyze the efficacy and safety of this approach based on a large number of multicenter cases.METHODS: This was a retrospective, multicenter cohort study from 14 centers in China. All patients were treated with the KD. We compared the effects of KD intervention time, age, and other factors.RESULTS: From March 2014 to March 2020, we treated 114 patients with DS with the KD. The male-to-female ratio was 67:47. The KD median initiation age was 3 y and 4 mo, and the median number of antiseizure medications (ASMs) was 2.4. KD therapy was the first choice for three patients. Exactly 10.5% of the patients started KD therapy after failure of the first ASM therapy, with 35.1% after failure of the second, 44.7% after the third, and 7% after the fourth or more. After KD therapy for 1, 3, 6, and 12 mo, the seizure-free rates were 14%, 32.5%, 30.7%, and 19.3%, respectively; KD efficacy (50% reduction in seizure frequency) were 57.9%, 76.3%, 59.6%, and 43%, respectively; the retention rates were 97.4%, 93%, 71.9%, and 46.5%, respectively; and the rates of adverse events were 25.2%, 19.9%, 11%, and 5.7%, respectively.CONCLUSIONS: Real-world, multicenter data analysis showed that the KD is effective for patients with DS and has a low incidence of side effects.

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PMID:  J Cell Mol Med. 2023 May ;27(10):1410-1422. Epub 2023 Apr 15. PMID: 37060584 Abstract Title:  A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression. Abstract:  The role of pescadillo1 (PES1) in regulating vascular permeability has been unknown. This study probes the role of PES1 and its mediated molecular mechanism in modulating vascular hyperpermeability in diabetic mice. Male C57BL/6J and db/db mice were fed a standard diet and a ketogenic diet (KD). Meanwhile, mouse vascular endothelial cells (MVECs) were treated with-hydroxybutyric acid (-HB), Pes1 siRNA or a Pes1 overexpression plasmid. Additionally, knockout (KO) of Pes1 in mice was applied. After 12weeks of feedings, enhanced vascular PES1 expression in diabetic mice was inhibited by the KD. The suppression of PES1 was also observed in-HB-treated MVECs. In mice with Pes1 KO, the levels of vascular VEGF and PES1 were attenuated, while the levels of vascular VE-cadherin, Ang-1 and Occludin were upregulated. Similar outcomes also occurred after the knockdown of Pes1 in cultured MVECs, which were opposite to the effects induced by PES1 overexpression in MVECs. In vitro and in vivo experiments showed that high glucose concentration-induced increases in vascular paracellular permeability declined after MVECs were treated by-HB or by knockdown of Pes1. In contrast, increases in vascular permeability were induced by overexpression of Pes1, which were suppressed by coadministration of-HB in cultured endothelial cells. Similarly declines in vascular permeability were found by Pes1 knockdown in diabetic mice. Mechanistically,-HB decreased PES1-facilitated ubiquitination of VE-cadherin. The KD suppressed the diabetes-induced increase in PES1, which may result in vascular hyperpermeability through ubiquitination of VE-cadherin in type 2 diabetic mice.

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PMID:  Mol Nutr Food Res. 2023 Jun ;67(11):e2200711. Epub 2023 Apr 25. PMID: 37052374 Abstract Title:  Ketogenic Diet Alleviates Hypoglycemia-Induced Neuroinflammation via Modulation the Gut Microbiota in Mice. Abstract:  SCOPE: This study aims to investigate the role of gut microbiota regulation with ketogenic diet (KD) in hypoglycemia-induced neuroinflammation.METHODS AND RESULTS: Immunofluorescence staining and western blotting show that KD alleviates blood-brain barrier injury induced by hypoglycemia by increasing Podxl and zonula occludens-1 (ZO-1) levels. KD-fed mice show reduced brain edema by decreasing aquaporin-4 (AQP4) content and maintaining its polarized expression. 16S rRNA gene amplicon sequencing results show that KD reduces the Chao 1 index of gut microbiota-diversity, and significant separation is detected in the-diversity analysis between the control and KD-fed mice. KD increases the relative abundance of Firmicutes and Proteobacteria and decreases that of Bacteroidetes. Hypoglycemia can reduce SOD and GSH-PX levels while increasing TNF-, IL-1, and IL-6 mRNA levels in the brain tissues of mice. KD alleviates hypoglycemia-induced neuroinflammation by inhibiting microglia activation and TLR4/p38MAPK/NF-B signaling pathway. Importantly, antibiotic cocktail depletion of the gut microbiota weakens anti-inflammatory and antioxidation responses in KD-fed mice.CONCLUSION: Collectively, these findings suggest that KD alleviates hypoglycemia-induced brain injury via gut microbiota modulation, which may provide novel insights into the therapy for hypoglycemia.

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PMID:  J Alzheimers Dis. 2023 ;92(4):1173-1198. PMID: 37038820 Abstract Title:  Ketogenic Diet as a Promising Non-Drug Intervention for Alzheimer's Disease: Mechanisms and Clinical Implications. Abstract:  Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is mainly characterized by cognitive deficits. Although many studies have been devoted to developing disease-modifying therapies, there has been no effective therapy until now. However, dietary interventions may be a potential strategy to treat AD. The ketogenic diet (KD) is a high-fat and low-carbohydrate diet with adequate protein. KD increases the levels of ketone bodies, providing an alternative energy source when there is not sufficient energy supply because of impaired glucose metabolism. Accumulating preclinical and clinical studies have shown that a KD is beneficial to AD. The potential underlying mechanisms include improved mitochondrial function, optimization of gut microbiota composition, and reduced neuroinflammation and oxidative stress. The review provides an update on clinical and preclinical research on the effects of KD or medium-chain triglyceride supplementation on symptoms and pathophysiology in AD. We also detail the potential mechanisms of KD, involving amyloid and tau proteins, neuroinflammation, gut microbiota, oxidative stress, and brain metabolism. We aimed to determine the function of the KD in AD and outline important aspects of the mechanism, providing a reference for the implementation of the KD as a potential therapeutic strategy for AD.

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PMID:  Front Nutr. 2023 ;10:1127845. Epub 2023 Mar 23. PMID: 37032786 Abstract Title:  Ketogenic diet alleviates renal fibrosis in mice by enhancing fatty acid oxidation through the free fatty acid receptor 3 pathway. Abstract:  INTRODUCTION: The ketogenic diet (KD), as a dietary intervention, has gained importance in the treatment of solid organ structural remodeling, but its role in renal fibrosis has not been explored.METHODS: Male C57BL/6 mice were fed a normal diet or a KD for 6 weeks prior to unilateral ureteral obstruction (UUO), a well-establishedmodel of renal fibrosis in rodents. Seven days after UUO, serum and kidney samples were collected. Serum-hydroxybutyrate (-OHB) concentrations and renal fibrosis were assessed. NRK52E cells were treated with TGF1, a fibrosis-inducing cytokine, and with or without-OHB, a ketone body metabolized by KD, to investigate the mechanism underlying renal fibrosis.RESULTS: KD significantly enhanced serum-OHB levels in mice. Histological analysis revealed that KD alleviated structural destruction and fibrosis in obstructed kidneys and reduced the expression of the fibrosis protein markers-SMA, Col1a1, and Col3a1. Expression of the rate-limiting enzymes involved in fatty acid oxidation (FAO), Cpt1a and Acox1, significantly decreased after UUO and were upregulated by KD. However, the protective effect of KD was abolished by etomoxir (a Cpt1a inhibitor). Besides, our study observed that KD significantly suppressed UUO-induced macrophage infiltration and the expression of IL-6 in the obstructive kidneys. In NRK52E cells, fibrosis-related signaling was increased by TGF1 and reduced by-OHB.-OHB treatment restored the impaired expression of Cpt1a. The effect of-OHB was blocked by siRNA targeting free fatty acid receptor 3 (FFAR3), suggesting that-OHB might function through the FFAR3-dependent pathway.DISCUSSION: Our results highlight that KD attenuates UUO-induced renal fibrosis by enhancing FAO via the FFAR3-dependent pathway, which provides a promising dietary therapy for renal fibrosis.

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PMID:  Pediatr Neurol. 2023 Jun ;143:79-83. Epub 2023 Mar 9. PMID: 37031571 Abstract Title:  Ketogenic Diet Attenuates Refractory Epilepsy of Harel-Yoon Syndrome With ATAD3A Variants: A Case Report and Review of Literature. Abstract:  BACKGROUND: Harel-Yoon syndrome is a disease caused by variants in the ATAD3A gene, which manifest as global developmental delay, hypotonia, intellectual disability, and axonal neuropathy. The aim of this study is to summarize the clinical and gene mutation characteristics of a child with refractory epilepsy caused by ATAD3A gene mutation.METHODS: The whole-exome sequencing combined with copy number variation analysis could help to understand the genetic diversity and underlying disease mechanisms in ATAD3A gene mutation.RESULTS: We report a Chinese boy with Harel-Yoon syndrome presenting with refractory epilepsy, hypotonia, global developmental delay, and congenital cataract through whole-exome sequencing. Genetic analysis showed a missense mutation, c.251T>C(p.Thr84Met) in the ATAD3A gene (NM_001170535.1). Further copy number variation analysis identified a novel heterozygous deletion on chromosome1p36.33, which spans ATAD3A exon 1 and 2 regions. Multiple antiepileptic drugs failed to control his seizures. Eventually, seizure was controlled through ketogenic diet (KD).CONCLUSION: Our case shows the potential diagnostic role of whole-exome sequencing in Harel-Yoon syndrome and expands the ATAD3A gene mutation spectrum. Multiple antiepileptic drugs failed to control refractory epilepsy in Harel-Yoon syndrome. The KD therapy may be effective for patients with refractory epilepsy who carry the ATAD3A variants.

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PMID:  J Nutr Biochem. 2023 Aug ;118:109335. Epub 2023 Apr 5. PMID: 37023933 Abstract Title:  Ketogenic diet alleviates renal interstitial fibrosis in UUO mice by regulating macrophage proliferation. Abstract:  The ketogenic diet (KD), a high-fat and extremely low-carbohydrate dietary regimen, has long been acknowledged as a highly beneficial dietary therapy for the treatment of intractable epilepsy throughout the last decade. Because of its significant therapeutic potential for a variety of ailments, KD is increasingly attracting study interest. In renal fibrosis, KD has received little attention. This study aimed to determine whether KD protects against renal fibrosis in unilateral ureteral obstruction (UUO) models and the possible mechanisms. The ketogenic diet, according to our findings, reduces UUO-induced kidney injury and fibrosis in mice. KD dramatically decreased the number of F4/80macrophages in kidneys. Next, immunofluorescence results revealed a reduction in the number of F4/80Ki67macrophages in the KD group. Furthermore, our study evaluated the impact of-hydroxybutyric acid (-OHB) in RAW246.7 macrophages in vitro. We found that-OHB inhibits macrophage proliferation. Mechanistically,-OHB inhibits macrophage proliferation may be via the FFAR3-AKT pathway. Collectively, our study indicated that KD ameliorates UUO-induced renal fibrosis by regulating macrophage proliferation. KD may be an effective therapy method for renal fibrosis due to its protective impact against the disorder.

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PMID:  Endocr Connect. 2023 Jul 1 ;12(7). Epub 2023 Jun 12. PMID: 37018117 Abstract Title:  Efficacy of very low-calorie ketogenic diet with the Pronokalmethod in obese women with polycystic ovary syndrome: a 16-week randomized controlled trial. Abstract:  OBJECTIVE: The aim of this study isto assess the efficacy of a very low-calorie ketogenic diet (VLCKD) method vs a Mediterranean low-calorie diet (LCD) in obese polycystic ovary syndrome (PCOS) women of a reproductive age.DESIGN: Randomized controlled open-label trial was performed in this study. The treatment period was 16 weeks; VLCKD for 8 weeks then LCD for 8 weeks, according to the Pronokalmethod (experimental group; n = 15) vs Mediterranean LCD for 16 weeks (control group; n = 15). Ovulation monitoring was carried out at baseline and after 16 weeks, while a clinical exam, bioelectrical impedance analysis (BIA), anthropometry, and biochemical analyses were performed at baseline, at week 8, and at week 16.RESULTS: BMI decreased significantly in both groups and to a major extent in the experimental group (-13.7% vs -5.1%, P = 0.0003). Significant differences between the experimental and the control groups were also observed in the reduction of waist circumference (-11.4% vs -2.9%), BIA-measured body fat (-24.0% vs -8.1%), and free testosterone (-30.4% vs -12.6%) after 16 weeks (P = 0.0008, P = 0.0176, and P = 0.0009, respectively). Homeostatic model assessment for insulin resistance significantly decreased only in the experimental group (P = 0.0238) but without significant differences with respect to the control group (-23% vs -13.2%, P>0.05). At baseline, 38.5% of participants in the experimental group and 14.3% of participants in the control group had ovulation, which increased to 84.6% (P = 0.031) and 35.7% (P>0.05) at the end of the study, respectively.CONCLUSION: In obese PCOS patients, 16 weeks of VLCKD protocol with the Pronokalmethod was more effective than Mediterranean LCD in reducing total and visceral fat, and in ameliorating hyperandrogenism and ovulatory dysfunction.SIGNIFICANCE STATEMENTS: To the best of our knowledge, this is the first randomized controlled trial on the use of the VLCKD method in obese PCOS. It demonstrates the superiority of VLCKD with respect to Mediterranean LCD in reducing BMI with an almost selective reduction of fat mass and a unique effect of VLCKD in reducing visceral adiposity, insulin resistance, and in increasing SHBG with a consequent reduction of free testosterone. Interestingly, this study also demonstrates the superiority of the VLCKD protocol in improving ovulation, whose occurrence increased by 46.1% in the group treated by the VLCKD method against a rise of 21.4% in the group treated by Mediterranean LCD. This study extends the therapeutic approach possibilities in obese...

PMID:  J Taibah Univ Med Sci. 2023 Oct ;18(5):1101-1107. Epub 2023 Mar 21. PMID: 37009396 Abstract Title:  Regulatory effects of ketogenic diet on the inflammatory response in obese Saudi women. Abstract:  OBJECTIVE: In recent years, the use of a ketogenic diet (KD) against obesity has gained popularity in KSA. This study was designed to determine the impact of KD on anthropometric indices and on the abnormal regulation of inflammatory activities in obese Saudi women. Moreover, we investigated the potential of beta-hydroxybutyrate (BHB) supplementation on the inhibition of pro-inflammatory activities.METHODS: We enrolled 31 Saudi women (aged, 35.3  8.4 years) with an average BMI of 33.96  4.44 kg/munderwent an 8-week KD (8KD) from January to March 2021. Changes in anthropometric measurements were collected at baseline and after 4-8 weeks of intervention. Compliance with the dietary regimen was monitored weekly by plasma BHB level.RESULTS: Twenty-nine females commenced the diets and 23 completed the study (a 79% completion rate). In comparison to pre-intervention, the 8KD resulted in a significant increase in the levels of plasma BHB (P 

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PMID:  Adv Exp Med Biol. 2023 ;1411:537-554. PMID: 36949325 Abstract Title:  Ketogenic Diet and Inflammation: Implications for Mood and Anxiety Disorders. Abstract:  The ketogenic diet, known as a low-carbohydrate, high-protein, and high-fat diet, drastically restrains the major source of energy for the body, forcing it to burn all excess fat through a process called ketosis-the breaking down of fat into ketone bodies. First suggested as a medical treatment for children suffering from epilepsy, this diet has gained increased popularity as a rapid weight loss strategy. Over the past few years, there have been numerous studies suggesting that the ketogenic diet may provide therapeutic effects for several psychiatric conditions such as mood- and anxiety-related disorders. However, despite significant progress in research, the mechanisms underlying its therapeutic effects remain largely unexplored and are yet to be fully elucidated. This chapter provides an in-depth overview of preclinical and clinical evidence supporting the use of a ketogenic diet in the management of mood and anxiety disorders and discusses its relationship with inflammatory processes and potential mechanisms of actions for its therapeutic effects.

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PMID:  Geroscience. 2023 Mar 18. Epub 2023 Mar 18. PMID: 36933143 Abstract Title:  Ketogenic diets initiated in late mid-life improved measures of spatial memory in male mice. Abstract:  Studies have shown ketogenic diets (KD) started from early middle-age improved health span and longevity in mice. KDs started later in life or administered intermittently may be more feasible and promote compliance. Therefore, this study sought to test if continuous or intermittent KDs started in late-middle-aged mice would improve cognition and motor function at advanced age. Eighteen-month-old male C57BL/6JN mice were assigned to an isocaloric control (CD), KD, or intermittent ketogenic (IKD, 3-day KD/week) diet. A panel of behavior tests were performed to assess cognitive and motor functions with aging. Y-maze alternation rate was higher for both IKD and KD mice at 23 months of age and for KD mice at 26 months indicating an improved spatial working memory. Twenty-six-month-old KD mice also showed better spatial learning memory in Barnes maze when compared to the CD. Improved grid wire hang performance was observed in aged IKD and KD versus CD mice indicating better muscle endurance under isometric contraction. A reduced level of circulating proinflammatory cytokines in aged KD (IL-6 and TNF-) and IKD (IL-6) mice may contribute to the phenotypic improvements observed with these interventions. This study demonstrates that when initiated at late-middle age, the KD improved measures of spatial memory and grid wire hang performance in aged male mice, with IKD showing results intermediate to the CD and KD groups.

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PMID:  Cureus. 2023 Feb ;15(2):e34526. Epub 2023 Feb 1. PMID: 36879703 Abstract Title:  Alleviation of Asthma Symptoms After Ketogenic Diet: A Case Report. Abstract:  Asthma is a chronic disease that affects the quality of life of patients, and asthma exacerbations are often a reason for hospitalization and activity limitations. Obesity has been linked to asthma as a risk and exacerbating factor. Evidence suggests that weight reduction has a positive effect on asthma control. However, there is also debate on the role of the ketogenic diet in asthma control. Here we present a case of asthma who reported markedly improved asthma after starting a ketogenic diet in the absence of any other lifestyle change. Over the four months on the ketogenic diet, the patient reported losing 20 kg of weight, reduction in blood pressure (without antihypertensives), and complete alleviation of asthma symptoms. This case report is important as the control of asthma after a ketogenic diet is not studied well in humans and therefore needs to be studied extensively.

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PMID:  Nutrients. 2023 Feb 6 ;15(4). Epub 2023 Feb 6. PMID: 36839183 Abstract Title:  The Effects of Eight Weeks' Very Low-Calorie Ketogenic Diet (VLCKD) on Liver Health in Subjects Affected by Overweight and Obesity. Abstract:  Very low-calorie ketogenic diets (VLCKD) are widely employed in successful weight-loss strategies. Herein, we evaluated the efficacy and safety of a VLCKD on non-alcoholic fatty liver disease (NAFLD) and parameters commonly associated with this condition in overweight and obese subjects who did not take any drugs. This prospective, real-life study included thirty-three participants who followed a VLCKD for 8 weeks. NAFLD was diagnosed using transient elastography (FibroScan). Data on anthropometric measurements, bioimpedance analysis, and biochemical assays were gathered both before and after the dietary intervention. BMI (kg/m) (from 33.846.55 to 30.896.38,

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PMID:  Int J Mol Sci. 2023 Feb 4 ;24(4). Epub 2023 Feb 4. PMID: 36834515 Abstract Title:  The Ketogenic Diet and Neuroinflammation: The Action of Beta-Hydroxybutyrate in a Microglial Cell Line. Abstract:  The ketogenic diet (KD), a diet high in fat and protein but low in carbohydrates, is gaining much interest due to its positive effects, especially in neurodegenerative diseases. Beta-hydroxybutyrate (BHB), the major ketone body produced during the carbohydrate deprivation that occurs in KD, is assumed to have neuroprotective effects, although the molecular mechanisms responsible for these effects are still unclear. Microglial cell activation plays a key role in the development of neurodegenerative diseases, resulting in the production of several proinflammatory secondary metabolites. The following study aimed to investigate the mechanisms by which BHB determines the activation processes of BV2 microglial cells, such as polarization, cell migration and expression of pro- and anti-inflammatory cytokines, in the absence or in the presence of lipopolysaccharide (LPS) as a proinflammatory stimulus. The results showed that BHB has a neuroprotective effect in BV2 cells, inducing both microglial polarization towards an M2 anti-inflammatory phenotype and reducing migratory capacity following LPS stimulation. Furthermore, BHB significantly reduced expression levels of the proinflammatory cytokine IL-17 and increased levels of the anti-inflammatory cytokine IL-10. From this study, it can be concluded that BHB, and consequently the KD, has a fundamental role in neuroprotection and prevention in neurodegenerative diseases, presenting new therapeutic targets.

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PMID:  Maedica (Bucur). 2022 Dec ;17(4):812-819. PMID: 36818275 Abstract Title:  Anti-Tumor Effect of the Ketogenic Diet against DMH-Induced Colon Cancer in Rats. Abstract:  Colon cancer is one of the most common malignancies with significant importance. Recent theories believe that cancers are metabolic diseases. Therefore, the role of metabolism in the prevention and treatment of cancer has been considered and the ketogenic diet is one example. In the present study, we evaluated the effect of the ketogenic diet and a high carbohydrate diet on tumor size and number, histopathology, and insulin level as well as VEGF level in 1, 2 dymethylhydrazine (DMH)-induced colon cancer in rats. Forty adult male Wistar rats were divided into four groups as follows: control, colon cancer, ketogenic diet, and high carbohydrate diet groups. For induction of colon cancer, 30 mg/kg of 1,2 DMH solution was injected subcutaneously twice a week for 24 weeks. The results showed that the ketogenic diet reduced tumor size, number, and histopathological changes as well as VEGF level (P

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PMID:  Neurotoxicology. 2023 May ;96:37-52. Epub 2023 Mar 23. PMID: 36965781 Abstract Title:  Vinpocetine prevents rotenone-induced Parkinson disease motor and non-motor symptoms through attenuation of oxidative stress, neuroinflammation and-synuclein expressions in rats. Abstract:  Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. Epidemiological reports showed a significant association between environmental toxicants-induced gut dysbiosis and PD. Neuroinflammation, mitochondrial dysfunction and decreased cerebral blood flow are hallmarks of PD. This study sought to evaluate the protective ability of vinpocetine (VIN), a neuroprotectant, on rotenone (ROT) (mitochondrial complex I inhibitor) induced PD in rats. Sixty male Sprague Dawley rats were randomly divided into six groups (n = 10) and treated orally as follows; group 1: vehicle (10 ml/kg); group 2: rotenone (10 mg/kg) + vehicle; group 3-5: vinpocetine (5, 10 or 20 mg/kg) + rotenone (10 mg/kg), respectively, or group 6: vinpocetine 20 mg/kg before behavioural assay for motor symptoms (fore-limb hanging test and open field test) and non-motor symptoms (working memory and learning capabilities in Y-maze/Morris water maze tasks, anxiety in hole board test and gut motility with intestinal transit time). Following treatment for 28 days, biochemical assays and immunostaining was performed. We examined the effect of vinpocetine on rotenone-induced oxidative stress and inflammatory markers. The pretreatment of rats with vinpocetine reversed rotenone-induced locomotor deficit, motor incoordination, cognition deficits and gut dysfunction. In addition, rotenone-induced a significant increase in the level of interleukin-6 and tumor necrotic factor-, oxidative stress markers, cholinergic signalling, gut dysfunction and haematologic dysfunctions which were attenuated by vinpocetine administration. Immunostainings showed that rotenone-induced dopamine neuron loss, microglia reactivity, astrocytes activation, toll-like receptor 4 (TLR4) and-synuclein (SNCA) expressions which were attenuated by vinpocetine administration. Findings from this study revealed a neuroprotective effect of vinpocetine on rotenone-induced PD through anti-neuroinflammatory and antioxidant mechanisms.

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PMID:  Metabolites. 2023 Apr 21 ;13(4). Epub 2023 Apr 21. PMID: 37110238 Abstract Title:  Thymoquinone Antifungal Activity againstOral Isolates from Patients in Intensive Care Units-An In Vitro Study. Abstract:  The number ofspp. infections and drug resistance are dramatically increasing worldwide, particularly among immunosuppressed patients, and it is urgent to find novel compounds with antifungal activity. In this work, the antifungal and antibiofilm activity of thymoquinone (TQ), a key bioactive constituent of black cumin seedL., was evaluated againsta WHO 'high-priority' pathogen. Then, its effect on the expression ofandgenes (related to biofilm adhesion and development, respectively) were analyzed. Swab samples were taken from the oral cavity of 90 hospitalized patients in ICU wards, transferred to sterile falcon tubes, and cultured on Sabouraud Dextrose Agar (SDA) and Chromagarfor presumptive identification. Next, a 21-plex PCR was carried out for the confirmation of species level.isolates underwent antifungal drug susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), amphotericin B (AMB), and TQ according to the CLSI microdilution method (M27, A3/S4). Biofilm formation was measured by an MTT assay.andgene expression was assessed by real-time PCR. From the 90 swab samples, 40 isolates were identified aswith the 21-plex PCR. Most isolates were resistant to FLZ (= 29, 72.5%), whereas 12.5% and 5% were ITZ and AMB resistant, respectively. The minimum inhibitory concentration (MIC) of TQ againstwas 50g/mL. Importantly, TQ significantly inhibited the biofilm formation ofisolates, andgene expression was reduced significantly at MICconcentration of TQ. TQ seems to have some antifungal, antibiofilm (adhesion) effect onisolates, showing that this plant secondary metabolite is a promising agent to overcomeinfections, especially oral candidiasis.

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PMID:  Antioxidants (Basel). 2023 Apr 1 ;12(4). Epub 2023 Apr 1. PMID: 37107234 Abstract Title:  Radical Scavenging Is Not Involved in Thymoquinone-Induced Cell Protection in Neural Oxidative Stress Models. Abstract:  Thymoquinone (TQ), an active compound fromseeds, is often described as a pharmacologically relevant compound with antioxidative properties, while the synthesis of TQ in the plant via oxidations makes it inapplicable for scavenging radicals. Therefore, the present study was designed to reassess the radical scavenging properties of TQ and explore a potential mode of action. The effects of TQ were studied in models with mitochondrial impairment and oxidative stress induced by rotenone in N18TG2 neuroblastoma cells and rotenone/MPPin primary mesencephalic cells. Tyrosine hydroxylase staining revealed that TQ significantly protected dopaminergic neurons and preserved their morphology under oxidative stress conditions. Quantification of the formation of superoxide radicals via electron paramagnetic resonance showed an initial increase in the level of superoxide radicals in the cell by TQ. Measurements in both cell culture systems revealed that the mitochondrial membrane potential was tendentially lowered, while ATP production was mostly unaffected. Additionally, the total ROS levels were unaltered. In mesencephalic cell culture under oxidative stress conditions, caspase-3 activity was decreased when TQ was administered. On the contrary, TQ itself tremendously increased the caspase-3 activity in the neuroblastoma cell line. Evaluation of the glutathione level revealed an increased level of total glutathione in both cell culture systems. Therefore, the enhanced resistance against oxidative stress in primary cell culture might be a consequence of a lowered caspase-3 activity combined with an increased pool of reduced glutathione. The described anti-cancer ability of TQ might be a result of the pro-apoptotic condition in neuroblastoma cells. Our study provides evidence that TQ has no direct scavenging effect on superoxide radicals.

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PMID:  Carcinogenesis. 2023 Apr 27. Epub 2023 Apr 27. PMID: 37105709 Abstract Title:  Thymoquinone inhibits lung cancer stem cell properties via triggering YAP degradation. Abstract:  Due to the characteristics of high recurrence and metastasis, it is still difficult to cure lung cancer. Cancer stem cells (CSCs) are a group of tumor cells with self-renewal ability and differentiation potential, which are responsible for lung cancer recurrence. Therefore, targeting CSCs may provide a new strategy for lung cancer treatment. Thymoquinone (TQ), the main active ingredient isolated from black seed oil, has shown significant anti-cancer effects in various cancers. However, the effects of TQ on lung cancer stem cells (LCSCs) has never been clarified. In the present study, we successfully separated and enriched lung cancer tumorsphere cells. Our data showed that TQ significantly inhibited the stem-like properties of LCSCs. In addition, we found TQ promoted Yes-associated protein (YAP) phosphorylation and ubiquitination, and the inhibitory effects of TQ on LCSCs could be enhanced by silencing YAP. Taken together, these results suggest that TQ, functions by targeting YAP, may be a potential therapeutic agent against lung cancer.

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PMID:  Eur Rev Med Pharmacol Sci. 2023 Mar ;27(6):2404-2418. PMID: 37013759 Abstract Title:  Studying the actions of sage and thymoquinone combination on metabolic syndrome induced by high-fat diet in rats. Abstract:  OBJECTIVE: High-fat diet is one of the most imperative risk factors for cardiovascular disorders. Thymoquinone (TQ) is one of the active pharmacological components of Nigella sativa (black cumin). Salvia officinalis L. (sage) has been demonstrated to have diverse pharmacological actions. The main objective of this study was to determine the effects of sage and TQ combination on hyperglycemia, oxidative stress, blood pressure, and lipid profile in rats fed with a high-fat diet (HFD).MATERIALS AND METHODS: Wistar male rats were divided into five groups; normal diet (ND) and HFD, in which rats were fed with a normal diet or HFD for 10 weeks, respectively. In HFD+sage group, animals were administered sage essential oil (0.052 ml/kg) orally along with HFD. In HFD+TQ group, rats were administered TQ (50 mg/kg) orally with HFD. In HF+sage + TQ group, animals received sage + TQ along with HFD. Blood glucose (BGL) and Fast serum insulin (FSI) levels, oral glucose tolerance test, blood pressure, liver function tests, plasma, and hepatic oxidative stress markers, antioxidant enzymes, and glutathione content, and lipid profile were measured.RESULTS: Sage and TQ combination decreased the final body weight, weight gain, BGL, FSI, and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The combination also lowered systolic and diastolic arterial pressures and liver function enzymes. The combination deterred lipid peroxidation, advanced protein oxidation product, and nitric oxide amplification, as well as restoring the superoxide dismutase, catalase activities, and glutathione content in plasma and hepatic tissue. Sage and TQ combination reduced the plasma total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels and amplified high-density lipoprotein (HDL).CONCLUSIONS: The results of the current study verified that sage essential oil, together with TQ exhibited hypoglycemic, hypolipidemic, and antioxidant actions and thus could be a valuable addition to diabetes management.

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PMID:  Antibiotics (Basel). 2023 Feb 10 ;12(2). Epub 2023 Feb 10. PMID: 36830281 Abstract Title:  Inhibitory Activity of Essential Oils ofandon Biofilms ofin an In Vitro Model. Abstract:  The aim of this study was to evaluate the inhibitory activity of the commercially available essential oils of(spearmint) and(eucalyptus) onATCC 25175 biofilms in vitro, emulating dental plaque conditions. The composition of the essential oils (EOs) was determined using gas chromatography coupled with mass spectrometry (GC-MS), with the main metabolites being Carvone (57.93%) and Limonene (12.91%) forand 1,8-Cineole (Eucalyptol) (65.83%) for. The inhibitory activity was evaluated using the methods of agar-well diffusion and colorimetric microdilution. The inhibition halos were 18.30.47 mm and 27.00.82 mm, and the MICs were 1.8484 mg/mL and 1.9168 mg/mL for the EOs ofandrespectively. The activity against the biofilms was evaluated on a substrate of bovine enamel pieces using a basal mucin medium (BMM) in anaerobic conditions with daily sucrose exposition cycles in order to emulate oral cavity conditions. The EOs were applied in a concentration of 0.5% in a sterile saline vehicle with 1% polysorbate 20. After 72 h of cultivation, a significant reduction was observed (

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PMID:  Nutrients. 2023 Mar 22 ;15(6). Epub 2023 Mar 22. PMID: 36986262 Abstract Title:  Repeated 28-Day Oral Toxicological Study and Gastroprotective Effects ofL. Oil (Shuhada) against Ethanol-Induced Gastric Mucosal Injury in Rats. Abstract:  L. and black seeds are traditionally used for cooking and medicinal purposes in Arab and other countries. Althoughseed extract has many known biological effects, the biological effects of cold-pressedoil are poorly understood. Therefore, the objective of this study was to investigate the gastroprotective effects and subacute oral toxicity of black seed oil (BSO) in an animal model. The gastroprotective effects of oral BSO (50% and 100%; 1 mg/kg) were tested using acute experimental models of ethanol-induced gastric ulcers. Gross and histological gastric lesions, ulcerated gastric areas, ulcer index score, percentage of inhibition rate, gastric juice pH, and gastric wall mucus were all evaluated. The subacute toxicity of BSO and its thymoquinone (TQ) content were also examined. The results indicated that the administration of BSO exerted gastroprotective effects by increasing the gastric wall mucus and decreasing gastric juice acidity. In the subacute toxicity test, the animals behaved normally, and their weight and water and food intake did not show significant variations. High-performance liquid chromatography detected 7.3 mg/mL TQ in BSO. These findings suggest that BSO may be a safe therapeutic drug for preventing gastric ulcers.

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PMID:  J Pharmacopuncture. 2023 Mar 31 ;26(1):1-9. PMID: 37007297 Abstract Title:  A Review of Clinical and Preclinical Studies on the Therapeutic Potential of Black Seeds () in the Management of Polycystic Ovarian Syndrome (PCOS). Abstract:  OBJECTIVES: Polycystic ovary syndrome (PCOS) is a condition that occurs frequently among women of reproductive age and is a polygenic, multifactorial, endocrine, and metabolic disorder. PCOS is becoming more common as a result of risk factors such as current lifestyle, overnutrition, and stress. The use of traditional herbal medicine is higher among the global population. Hence, this review article focuses on the potential ofto manage women with PCOS.METHODS: A literature search was carried out using databases including Medline, Google Scholar, EBSCO, Embase, and Science Direct, as well as reference lists, to identify relevant publications that support the use ofin the management of women with PCOS.RESULTS: Several clinical and preclinical studies have demonstrated that the major bioactive constituent of black seed (), thymoquinone, has potential for managing women with PCOS. Moreover,may help to manage oligomenorrhea and amenorrhea in women with PCOS through its anti-inflammatory and antioxidant properties.CONCLUSION: has potential for use as a herbal medicine for managing women with PCOS as an integrative medicine along with traditional and modern medicine in conjunction with calorie restriction and regular exercise.

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PMID:  Int Immunopharmacol. 2023 Jun ;119:110221. Epub 2023 Apr 28. PMID: 37121114 Abstract Title:  Piperine ameliorates psoriatic skin inflammation by inhibiting the phosphorylation of STAT3. Abstract:  Psoriasis is a common chronic inflammatory skin disease that is easy to relapse and difficult to cure. Piperine is the main alkaloid extracted from black pepper, and its role in psoriasis has not been previously reported. We identified that piperine ameliorated M5-induced psoriatic skin lesions. Furthermore, piperine alleviated psoriasis pathological features including epidermal hyperplasia and inflammatory cell infiltration, decreased the expression of psoriasis-characteristic cytokines, chemokines and proteins in IMQ-induced psoriasiform dermatitis. Moreover, we determined that piperine inhibited the phosphorylation of STAT3 in M5- and IMQ-induced psoriasis-like skin lesions. Our data demonstrated that piperine ameliorated psoriatic skin inflammation by inhibiting the phosphorylation of STAT3. Therefore, piperine may be one potential compound candidate for psoriasis therapy, providing new strategies for clinical intervention.

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PMID:  J Orthop Surg Res. 2023 Mar 9 ;18(1):180. Epub 2023 Mar 9. PMID: 36895009 Abstract Title:  Piperine improves the sensitivity of osteosarcoma cells to doxorubicin by inducing apoptosis and inhibiting the PI3K/AKT/GSK-3pathway. Abstract:  BACKGROUND: Osteosarcoma is a primary bone malignancy associated with the highest incidence rate. Chemotherapy for osteosarcoma has not substantially changed, and survival of patients with metastatic tumours has reached a plateau. Doxorubicin (DOX) is a broad-spectrum anti-osteosarcoma drug; however, its application is limited due to its high cardiotoxicity. Piperine (PIP) has been verified to drive certain cancer cell death and increases chemosensitivity of DOX. However, the effects of PIP in promoting the chemosensitivity of osteosarcoma to DOX have not been studied.METHODS: We examined the combined effect of PIP and DOX on U2OS and 143B osteosarcoma cells. CCK-8 assays, scratch assays, flow cytometry analysis, and western blotting were performed. Furthermore, the effect of PIP combined with DOX on osteosarcoma tumours was observed in vivo using nude mice.RESULTS: PIP can increase the chemosensitivity of U2OS and 143B cells to DOX. Both in vitro and in vivo results showed the dramatic inhibition of cell proliferation and tumour growth by the combined therapy group compared to monotherapy groups. Apoptosis analysis revealed that PIP augments DOX-induced cell apoptosis by upregulating BAX and P53 expression, as well as reducing Bcl-2 expression. Furthermore, PIP also attenuated the initiation of the PI3K/AKT/GSK-3signaling pathway in osteosarcoma cells by altering the expression levels of P-AKT, P-PI3K and P-GSK3.CONCLUSIONS: This study revealed for the first time that PIP can potentiate the sensitivity and cytotoxicity of DOX during osteosarcoma therapy in vitro and in vivo, which probably achieved by inhibiting the PI3K/AKT/GSK-3signalling pathway.

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PMID:  CMAJ. 2023 May 1 ;195(17):E601-E611. PMID: 37127306 Abstract Title:  Hourly air pollution exposure and the onset of symptomatic arrhythmia: an individual-level case-crossover study in 322 Chinese cities. Abstract:  BACKGROUND: Few studies have explored the relationship between air pollution and arrhythmia onset at the hourly level. We aimed to examine the association of exposure to air pollution with the onset of acute symptomatic arrhythmia at an hourly level.METHODS: We conducted a nationwide, time-stratified, case-crossover study in China between 2015 and 2021. We obtained hourly information on the onset of symptomatic arrhythmia (including atrial fibrillation, atrial flutter, atrial and ventricular premature beats and supraventricular tachycardia) from the Chinese Cardiovascular Association Database - Chest Pain Center (including 2025 certified hospitals in 322 cities). We obtained data on hourly concentrations of 6 air pollutants from the nearest monitors, including fine particles (PM), coarse particles (PM), nitrogen dioxide (NO), sulfur dioxide (SO), carbon monoxide (CO) and ozone. For each patient, we matched the case period to 3 or 4 control periods during the same hour, day of week, month and year. We used conditional logistic regression models to analyze the data.RESULTS: We included a total of 190 115 patients with acute onset of symptomatic arrhythmia. Air pollution was associated with increased risk of onset of symptomatic arrhythmia within the first few hours of exposure; this risk attenuated substantially after 24 hours. An interquartile range increase in PM, NO, SOand CO in the first 24 hours after exposure (i.e., lag period 0-24 h) was associated with significantly higher odds of atrial fibrillation (1.7%-3.4%), atrial flutter (8.1%-11.4%) and supraventricular tachycardia (3.4%-8.9%). Exposure to PMwas associated with significantly higher odds of atrial flutter (8.7%) and supraventricular tachycardia (5.4%), and exposure to ozone was associated with higher odds of supraventricular tachycardia (3.4%). The exposure-response relationships were approximately linear, without discernible concentration thresholds.INTERPRETATION: Exposure to air pollution was associated with the onset of symptomatic arrhythmia shortly after exposure. This finding highlights the importance of further reducing air pollution and taking prompt protective measures for susceptible populations during periods of elevated levels of air pollutants.

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PMID:  Sci Total Environ. 2023 Aug 1 ;884:163802. Epub 2023 Apr 29. PMID: 37127163 Abstract Title:  Long-term residential exposure to air pollution and risk of chronic respiratory diseases in Italy: The BIGEPI study. Abstract:  Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM, PM), nitrogen dioxide (NO), and summer ozone (O) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean  SD exposures were 28.7  6.0 g/m(PM), 20.1  5.6 g/m(PM), 27.2  9.7 g/m(NO), and 70.8  4.2 g/m(summer O). The concentrations of PM, PM, and NOwere higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM: OR 1.62, 95%CI: 1.19-2.20 and PM: OR 1.80, 95%CI: 1.16-2.81, per 10 g/m) and between NOexposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 g/m), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO, a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD.

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PMID:  Infect Dis Model. 2023 Jun ;8(2):390-402. Epub 2023 Mar 29. PMID: 37124150 Abstract Title:  The influence of ambient air pollution on the transmission of tuberculosis in Jiangsu, China. Abstract:  In this paper, based on the statistical data, we investigate the effects of long-term exposure to ambient particulate air pollution on the transmission dynamics of tuberculosis (TB) in Jiangsu, China by studying the threshold dynamics of the TB epidemic model via the statistical data analytically and numerically. The basic reproduction numberreveals that TB in Jiangsu, China is an endemic disease and will persist for a long time. And the numerical results show that, in order to control the TB in Jiangsu effectively, we must decrease the depuration coefficient of PMin the body, the proportion of TB symptomatic infectious by direct transmission, the reactivation rate of the pre-symptomatic infectious and the effect coefficient of PMand MTB inhaled of TB transmission, and increase the uptake coefficient, the recovery rate of the symptomatic/pre-symptomatic infectious and the influence coefficient of PMon the body of mortality. Our study shows that PMis closely related to the incidence of TB, and the effective control efforts are suggested to focus on increasing close-contact distance and wearing protective mask to decrease the influence of PMon the TB transmission, which may shed a new light on understanding the environmental drivers to TB.

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PMID:  Ecotoxicol Environ Saf. 2023 Jun 15 ;258:114962. Epub 2023 Apr 28. PMID: 37121078 Abstract Title:  Air pollution weaken your muscle? Evidence from a cross-sectional study on sarcopenia in central China. Abstract:  BACKGROUND: As the world experiences a demographic shift towards aging populations, there will be a significant surge in the number of sarcopenia patients, along with an unprecedented expansion in the associated economic burden. The multitudinous risk factors for sarcopenia have been reported, but evidence for air pollution remains rare.METHODS: This cross-sectional study employed multi-stage random sampling to select 1592 participants over 40 years of age from Hubei Province. Daily mean concentrations of air pollutants were collected ChinaHighAirPollutants dataset. Unconditional logistic regression models were utilized to investigate the associations between air pollution and sarcopenia.RESULTS: For each 1 g/mincrease in PM, PM, SOand O, there were corresponding elevations of 11.1% [95% confidence interval (CI): 4.9, 17.7], 4.3% (95% CI: 1.4, 7.2), 22.6% (95% CI: 7.2, 40.1) and 9.3% (95% CI: 0.7, 18.7) in the risk of sarcopenia, respectively. The associations of PM/PM/O-sarcopenia were more pronounced in females, with corresponding odds ratios (ORs) and 95% CIs of 1.179 (1.062, 1.310), 1.079 (1.027, 1.135) and 1.180 (1.026, 1.358), separately. Additionally, individuals residing in rural areas were more susceptible to the effects of PMand PM. Current/ever smokers or drinkers were also at higher risk of developing sarcopenia caused by PM, PMand Oexposure. Mixture analyses show a surge of 48.4% (95% CI: 3.6%, 112.5%) in the likelihood of suffering from sarcopenia, and the joint impacts of the air pollution were mainly driven by PM.CONCLUSIONS: Our results produced evidence for a relationship between air pollution exposure and the increased prevalence of sarcopenia in China. Public health and relevant departments should make efforts to prevent sarcopenia, particularly in China experiencing rapid demographic aging.

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PMID:  Phytomedicine. 2023 Jul ;115:154776. Epub 2023 Mar 18. PMID: 37087793 Abstract Title:  Ginsenoside Rbfor overcoming cisplatin-insensitivity of A549/DDP cells in vitro and vivo through the dual-inhibition on two efflux pumps of ABCB1 and PTCH1. Abstract:  BACKGROUND: The multi-drug resistance is an inherent weakness in the chemotherapeutics of non-small cell lung cancer occurring frequently all over the world. Clinically, ginseng and Chinese medicinal prescriptions including ginseng usually used as anti-tumor adjuncts due to its characteristic of qi-invigorating, which could improve the curative effect of chemotherapy drugs and reduce their toxic side effects. Triterpenoid saponins are the crucial active ingredients in Panax ginseng, and Ginsenoside Rbis of the highest quantities. However, the research on the tumor drug-resistance reversal effect and mechanism of ginsenoside Rbis still not clear.PURPOSE: This study aimed to systematically estimate the reversal activity of Ginsenoside Rbon cisplatin-insensitivity of A549/DDP cells and to reveal its prospective molecular mechanism.METHODS: MTT assay were conducted to evaluate the reversal activity on cisplatin-insensitivity of A549/DDP cells of Ginsenoside Rbin vitro, and the behavior was also studied by establishing a subcutaneous transplanted tumor model of A549/DDP in BALB/c-nu mice. In addition, P-gp ATPase activity assay, cisplatin accumulation assay, Annexin V-FITC apoptosis assay, real-time qPCR analysis and western blotting analysis were used to clarify the potential mechanism.RESULTS: Ginsenoside Rbcould effectively reverse the cisplatin-resistance of A549/DDP in vitro and vivo. And after the co-treatment of Ginsenoside Rbplus cisplatin, the accumulation of cisplatin increased in A549/DDP cells, which was accompanied with the down-regulation of the mRNA and protein expression levels of ABCB1, SHH, PTCH1 and GLI2. Besides, the apoptosis-inducing ability of cisplatin improved by the relative regulation on the protein expression level of Bax and Bcl-2. Far more importantly, the changes of CYP3A4 mRNA and protein levels were not significant.CONCLUSION: Ginsenoside Rbcould increase the concentration of intracellular cisplatin and improve the insensitivity for cisplatin on A549/DDP cells. Even better, there was perhaps no unpredictable CYP3A4-mediated pharmacokinetic interactions after the combination of Ginsenoside Rbplus cisplatin. Ginsenoside Rbwas a probable reversal agent for the cisplatin-insensitivity of A549/DDP cells, with a bifunction of inhibiting the efflux of two drug pumps (P-gp and PTCH1) by targeting ABCB1 and Hedgehog (Hh) pathway. In general, this research laid the groundwork for the development of a new reversal agent for the cisplatin-insensitivity of NSCLC.

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PMID:  Phytomedicine. 2023 Jul ;115:154827. Epub 2023 Apr 21. PMID: 37087792 Abstract Title:  Total saponins from Panax japonicus reduce inflammation in adipocytes through the miR155/SOCS1/NFB signaling pathway. Abstract:  BACKGROUND: The rising incidence of metabolic diseases due to chronic inflammation in the adipose tissue has been attributed to factors such as high fat diet (HFD). Previous studies have demonstrated that the total saponins from Panax japonicus (TSPJ) can reduce HFD-induced adipocyte inflammation, but the underlying mechanism remains unclear. In this work, we explored the molecular mechanism by which TSPJ reduces inflammation response in adipocytes.METHODS: We first established C57BL/6 mouse and 3T3-L1 adipocyte models. Lentiviruses packaged with the plasmids were injected into mice through the tail vein or into adipocytes to generate the in vivo and in vitro models with miR155 knockdown and overexpression. The mice were fed with HFD to trigger inflammation and administered TSPJ (25 mg/kgd and 75 mg/kgd) by gavage. The adipocytes were treated with palmitic acid (PA) to trigger inflammation response, then treated with TSPJ (25g/ml and 50g/ml). Finally, the expression of miR155, inflammatory factors, SOCS1, and NFB pathway-related proteins was explored.RESULTS: TSPJ significantly inhibited the expression of inflammation-related genes and the miR155 expression in adipocytes both in vitro and in vivo. The dual luciferase reporter gene assay revealed that miR155 mediated the downregulation of SOCS1. TSPJ significantly inhibited and upregulated the phosphorylation of the NFB protein and the SOCS1 proteins, respectively.CONCLUSION: TSPJ inhibits miR155 to upregulate the SOCS1 expression, which subsequently inhibits the NFB signaling pathway, thereby mitigating the inflammatory response in the adipocytes of HFD mice.

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PMID:  BMC Complement Med Ther. 2023 Apr 21 ;23(1):129. Epub 2023 Apr 21. PMID: 37085826 Abstract Title:  Panax quinquefolius saponin inhibits vascular smooth muscle cell calcification via activation of nuclear factor-erythroid 2-related factor 2. Abstract:  BACKGROUND: Panax quinquefolius saponin (PQS) is the main active component of Panax quinquefolius. Emerging evidence suggests that PQS exerts beneficial effects against cardiovascular diseases. However, the role and mechanism of PQS in vascular calcification are not unclear. The present study investigated the effects of PQS on the calcification of vascular smooth muscle cell (VSMCs).METHODS: The present study used calcification medium containing 3 mM inorganic phosphate (Pi) to induce rat VSMCs calcification. We investigated the effects of PQS on VSMCs calcification using alizarin red staining and alkaline phosphatase (ALP) activity assays. The intracellular reactive oxygen species (ROS) levels and the transcriptional activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined. The mRNA and protein expression levels of Nrf2, the antioxidant gene heme oxygenase-1 (HO-1), osteogenic markers, including runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2), and Kelch-like ECH-associated protein 1 (Keap1) were also measured.RESULTS: Treatment with Pi significantly increased intracellular calcium deposition and ALP activity, which were suppressed by PQS in a concentration-dependent manner. During VSMCs calcification, PQS inhibited the mRNA and protein expression of Runx2 and BMP2. PQS treatment reduced intracellular ROS production and significantly upregulated Nrf2 transcriptional activity and the expression of Nrf2 and its target antioxidant gene HO-1. PQS suppressed the Pi-induced protein expression of Keap1, which is an endogenous inhibitor of Nrf2. Keap1 siRNA treatment induced Nrf2 expression and downregulated Runx2 expression in the presence of Pi and PQS.CONCLUSION: Taken together, these findings suggest that PQS could effectively inhibit VSMCs calcification by ameliorating oxidative stress and regulating osteogenic genes via the promotion of Nrf2 expression.

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PMID:  Planta Med. 2023 Jun ;89(7):764-772. Epub 2023 Mar 20. PMID: 36940929 Abstract Title:  LC-MS Analysis of Ginsenosides in Different Parts of Panax quinquefolius and Their Potential for Coronary Disease Improvement. Abstract:  Seven main ginsenosides, including ginsenoside Re, ginsenoside Rb, pseudoginsenoside F, ginsenoside Rb, ginsenoside Rb, ginsenoside Rd, and ginsenoside F, were identified by LC-QTOF MS/MS from root, leaf and flower extracts of. These extracts promoted intersegmental vessel growth in a zebrafish model, indicating their potential cardiovascular health benefits. Network pharmacology analysis was then conducted to reveal the potential mechanisms of ginsenoside activity in the treatment of coronary artery disease. GO and KEGG enrichment analyses elucidated that G protein-coupled receptors played a critical role in VEGF-mediated signal transduction and that the molecular pathways associated with ginsenoside activity are involved in neuroactive ligand-receptor interaction, cholesterol metabolism, the cGMP-PKG signaling pathway, etc. Moreover, VEGF, FGF2, and STAT3 were confirmed as the major targets inducing proliferation of endothelial cells and driving the pro-angiogenic process. Overall, ginsenosides could be potent nutraceutical agents that act to reduce the risks of cardiovascular disease. Our findings will provide a basis to utilize the wholeplant in drugs and functional foods.

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PMID:  J Ethnopharmacol. 2023 Mar 1 ;303:115997. Epub 2022 Dec 9. PMID: 36509256 Abstract Title:  Ginsenoside Rb1 protects against diabetes-associated metabolic disorders in Kkay mice by reshaping gut microbiota and fecal metabolic profiles. Abstract:  ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolius Linn. is one of the most valuable herbal medicine in the world for its broad health benefits, including anti-diabetes. Ginsenoside Rb1, the principal active constituent of Panax quinquefolius Linn., could attenuate insulin resistance and metabolic disorders. The dysfunction of gut microbiota and fecal metabolites plays an important role in the pathogenesis of Type 2 Diabetes mellitus (T2DM). However, whether ginsenoside Rb1's hypoglycemic effect is related to gut microbiota remains elusive.AIM OF THE STUDY: Our study aimed to explore the insulin-sensitizing and anti-diabetic effects of ginsenoside Rb1 as well as the underlying mechanisms.MATERIALS AND METHODS: The T2DM model were established by high fat diet (HFD)-induced Kkay mice. The anti-diabetic effect of ginsenoside Rb1 (200 mg/kg/day) was evaluated by random blood glucose (RBG), fasting blood glucose (FBG), glucose tolerance test (OGTT), serum insulin level, insulin resistance index (HOMA-IR), pancreatic histology analysis, liver indexes, total triglyceride (TG) and total cholesterol (TC). Subsequently, 16S rRNA sequencing and LC-MS-based untargeted metabolomics were applied to characterize the microbiome and metabolites profile in HFD-induced Kkay mice, respectively. Finally, antibiotic treatment was used to validate the potential mechanism of ginsenoside Rb1 by modulating gut microbiota.RESULTS: Our results showed that ginsenoside Rb1 reduced blood glucose, OGTT, serum insulin level, HOMA-IR, liver indexes as well as pancreatic injury. In addition, the ginsenoside Rb1 reversed the gut microbiota dysbiosis in diabetic Kkay mice, as indicated by the elevated abundance of Parasutterella, decreased population of Alistipes, f_Prevotellaceae_unclassified, Odoribacter, Anaeroplasma. Moreover, ginsenoside Rb1 altered free fatty acid (FFA) levels in fecal metabolites, such as decreased the level of-linolenic acid, 13-OxoODE, oleic acid, 13-HODE, arachidonic acid, palmitic acid, stearic acid, while increased the level of PC (14:0/22:1(13Z)) and PC (16:0/16:0). Notably, ginsenoside Rb1 failed to improve HFD-induced diabetes in Kkay mice with antibiotics intervention.CONCLUSION: These findings suggested that ginsenoside Rb1 may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play essential roles in diabetes-associated metabolic disorders and insulin resistance.

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PMID:  Curr Pharm Biotechnol. 2023 Apr 17. Epub 2023 Apr 17. PMID: 37073148 Abstract Title:  Panax Notoginseng Saponins Alleviate LPS-induced Fibrosis of HK-2 Cells by Inhibiting the Activation of NLRP3 Inflammasome and Pyroptosis. Abstract:  BACKGROUND: Renal fibrosis is related to impaired kidney function and can eventually lead to end-stage renal disease, for which no effective treatment is available. Panax notoginseng saponins (PNS), as a commonly used traditional Chinese medicine, is considered a possible alternative for the treatment of fibrosis.OBJECTIVE: The purpose of the present study was to investigate the effects and possible mechanisms of PNS on renal fibrosis.METHODS: HK-2 cells were used to induce renal fibrosis cell model by lipopolysaccharide (LPS), and the cytotoxicity of PNS on HK-2 cells was investigated. Cell damage, pyroptosis, and fibrosis were analyzed to investigate the effects of PNS on LPS-induced HK-2 cells. NLRP3 agonist Nigericin was used further to explore the inhibitory effect of PNS on LPS-induced pyroptosis so as to clarify the possible mechanism of PNS on renal fibrosis.RESULTS: PNS had no cytotoxicity on HK-2 cells, and could reduce the apoptosis and the release of lactate dehydrogenase (LDH) and inflammatory cytokines of LPS-induced HK-2 cells, showing an alleviating effect on cell damage. PNS also reduced the expression of pyroptosis proteins NLRP3, IL-1, IL-18, and Caspase-1, as well as fibrosis proteins-SMA, collagenand p-Smad3/Smad3, which showed an inhibitory effect on LPS-induced pyroptosis and fibrosis. In addition, LPS-induced cell damage, pyroptosis, and fibrosis were aggravated after Nigericin treatment, while PNS alleviated the aggravation caused by Nigericin.CONCLUSION: PNS inhibits pyroptosis by inhibiting the activation of NLRP3 inflammasome in LPS-induced HK-2 cells, which ultimately alleviates renal fibrosis and plays a good role in the treatment of kidney diseases.

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PMID:  Phytother Res. 2023 Apr 18. Epub 2023 Apr 18. PMID: 37070654 Abstract Title:  Prevention effect of total ginsenosides and ginseng extract from Panax ginseng on cyclophosphamide-induced immunosuppression in mice. Abstract:  Oral decoction is widely applied in traditional Chinese medicines. The polysaccharides of decoction promote the exposure of small molecules and increase their bioavailability. This study mainly compared the component and activities of total ginsenosides (TGS) and ginseng extract (GE) on immunosuppressed mice induced by cyclophosphamide. Thirty-two mice were randomly divided into control, model, TGS, and GE groups. The mice were orally administered for 28days and then injected with cyclophosphamide on the last four days. The results of component analysis showed the total content of 12 ginsenosides in TGS (67.21%) was higher than GE (2.04%); the total content of 17 amino acids in TGS (1.41%) was lower than GE (5.36%); the total content of 10 monosaccharides was similar in TGS (74.12%) and GE (76.36%). The animal results showed that both TGS and GE protected the hematopoietic function of bone marrow by inhibiting cell apoptosis, and recovering the normal cell cycle of BM; maintained the dynamic balance between the Th1 and Th2 cells; also protected the spleen, thymus, and liver. Meanwhile, TGS and GE protected the intestinal bacteria of immunosuppressed mice by increasing the abundance of lactobacillus and decreasing the abundance of the odoribacter and clostridia_UCG-014. The prevention effect of GE was superior to TGS in some parameters. In conclusion, TGS and GE protected the immune function of immunosuppressed mice induced by cyclophosphamide. Meanwhile, GE showed higher bioavailability and bioactivity compared with TGS, because the synergistic effect of polysaccharides and ginsenosides plays an important role in protecting the immune function.

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PMID:  PLoS One. 2023 ;18(4):e0284398. Epub 2023 Apr 17. PMID: 37068063 Abstract Title:  Ginseng-containing traditional medicine preparations in combination with fluoropyrimidine-based chemotherapy for advanced gastric cancer: A systematic review and meta-analysis. Abstract:  BACKGROUND: Ginseng-containing traditional medicine preparations (G-TMPs) in combination with fluoropyrimidine-based chemotherapy (FBC) are well-known treatments for advanced gastric cancer (AGC), with a superior efficacy to FBC alone. However, evidence regarding their efficacy remains limited. The purpose of this meta-analysis is to evaluate the efficacy and safety of G-TMPs in combination with FBC for the treatment of AGC.METHODS: Eight electronic databases were searched for randomized controlled trials (RCTs) using G-TMPs with FBC for the treatment of AGC. The primary outcome included the tumor response, while the secondary outcomes included the quality of life (QoL), proportions of peripheral blood lymphocytes, adverse drug reactions (ADRs), and levels of cancer biomarkers. The quality of evidence for each outcome was assessed using GRADE profilers.RESULTS: A total of 1,960 participants were involved in the 26 RCTs included. Patients treated with FBC plus G-TMPs had better objective response (risk ratio [RR] = 1.23, 95% confidence interval [CI]: 1.13 to 1.35, p

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PMID:  Phytomedicine. 2023 Jun ;114:154787. Epub 2023 Mar 29. PMID: 37060724 Abstract Title:  Panax notoginseng saponins normalises tumour blood vessels by inhibiting EphA2 gene expression to modulate the tumour microenvironment of breast cancer. Abstract:  BACKGROUND: Panax notoginseng saponins (PNS), the main active component of Panax notoginseng, can promote vascular microcirculation. PNS exhibits antitumor effects in various cancers. However, the molecular basis of the relationship between PNS and tumor blood vessels remains unclear.PURPOSE: To study the relationship between PNS inhibiting the growth and metastasis of breast cancer and promoting the normalization of blood vessels.METHODS: We performed laser speckle imaging of tumor microvessels and observed the effects of PNS on tumor growth and metastasis of MMTV-PyMT (FVB) spontaneous breast cancer in a transgenic mouse model. Immunohistochemical staining of Ki67 and CD31 was performed for tumors, scanning electron microscopy was used to observe tumor vascular morphology, and flow cytometry was used to detect tumor tissue immune microenvironment (TME). RNA-seq analysis was performed using the main vessels of the tumor tissues of the mice. HUVECs were cultured in tumor supernatant in vitro to simulate tumor microenvironment and verify the sequencing differential key genes.RESULTS: After treatment with PNS, we observed that tumor growth was suppressed, the blood perfusion of the systemic tumor microvessels in the mice increased, and the number of lung metastases decreased. Moreover, the vascular density of the primary tumor increased, and the vascular epidermis was smoother and flatter. Moreover, the number of tumor-associated macrophages in the tumor microenvironment was reduced, and the expression levels of IL-6, IL-10, and TNF-were reduced in the tumor tissues. PNS downregulated the expression of multiple genes associated with tumor angiogenesis, migration, and adhesion. In vitro tubule formation experiments revealed that PNS promoted the formation and connection of tumor blood vessels and normalized the vessel morphology primarily by inhibiting EphA2 expression. In addition, PNS inhibited the expression of tumor vascular marker proteins and vascular migration adhesion-related proteins in vivo.CONCLUSION: In this study, we found that PNS promoted the generation and connection of tumor vascular endothelial cells, revealing the key role of EphA2 in endothelial cell adhesion and tumor blood vessel morphology. PNS can inhibit the proliferation and metastasis of breast cancer by inhibiting EphA2, improving the immune microenvironment of breast cancer and promoting the normalization of tumor blood vessels.

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PMID:  Nutrients. 2023 Mar 31 ;15(7). Epub 2023 Mar 31. PMID: 37049554 Abstract Title:  Photoprotective Effect of Fermented and Aged Mountain-Cultivated Ginseng Sprout () on Ultraviolet Radiation-Induced Skin Aging in a Hairless Mouse Model. Abstract:  Interest in foods that promote inner beauty increases with increases in exposure to ultraviolet (UV) rays and with improvements in quality of life. This study was performed to evaluate the efficacy of fermented and aged mountain-cultivated ginseng sprouts (FAMCGSs), which have higher anti-inflammatory and antioxidant effects compared to mountain-cultivated ginseng sprouts (MCGSs), as an inner beauty enhancing food. The effect of orally administered FAMCGSs on UV type B (UVB) radiation-induced skin aging was investigated in a hairless mouse model through analyzing skin parameters including epidermal thickness, transepidermal water loss (TEWL), roughness, moisture, elasticity, and collagen contents. The mice exposed to UVB had markedly greater epidermal thickness, TEWL, and skin roughness than those of the normal control (NC) group. In addition, the levels of collagen, skin moisture, and dermal elasticity were lower in the UVB radiation group than the NC group. These UVB-induced skin aging parameters were significantly lower in the groups administered FAMCGSs than in the groups not administered FAMCGSs (

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Judge says there is "substantial evidence" the government violated the First Amendment by censoring content that questioned or countered establishment narratives on COVID-19

Have you heard about the latest injunction ruling making headlines? The one where a federal judge is finally putting a spanner in the works of the Biden administration's illegal collusion with Big Tech companies to suppress the free and truthful speech of Americans?

"In his 155-page ruling, Judge Terry Doughty said there is "substantial evidence" the government violated the First Amendment by engaging in a large-scale censorship campaign targeting content that questioned or countered establishment narratives on COVID-19."

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PMID:  Int J Mol Sci. 2023 Mar 24 ;24(7). Epub 2023 Mar 24. PMID: 37047092 Abstract Title:  Ginsenosides fromas Key Modulators of NF-B Signaling Are Powerful Anti-Inflammatory and Anticancer Agents. Abstract:  Nuclear factor kappa B (NF-B) signaling pathways progress inflammation and immune cell differentiation in the host immune response; however, the uncontrollable stimulation of NF-B signaling is responsible for several inflammatory illnesses regardless of whether the conditions are acute or chronic. Innate immune cells, such as macrophages, microglia, and Kupffer cells, secrete pro-inflammatory cytokines, such as TNF-, IL-6, and IL-1, via the activation of NF-B subunits, which may lead to the damage of normal cells, including neurons, cardiomyocytes, hepatocytes, and alveolar cells. This results in the occurrence of neurodegenerative disorders, cardiac infarction, or liver injury, which may eventually lead to systemic inflammation or cancer. Recently, ginsenosides from, a historical herbal plant used in East Asia, have been used as possible options for curing inflammatory diseases. All of the ginsenosides tested target different steps of the NF-B signaling pathway, ameliorating the symptoms of severe illnesses. Moreover, ginsenosides inhibit the NF-B-mediated activation of cancer metastasis and immune resistance, significantly attenuating the expression of MMPs, Snail, Slug, TWIST1, and PD-L1. This review introduces current studies on the therapeutic efficacy of ginsenosides in alleviating NF-B responses and emphasizes the critical role of ginsenosides in severe inflammatory diseases as well as cancers.

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PMID:  Curr Res Food Sci. 2023 ;6:100491. Epub 2023 Mar 21. PMID: 37033737 Abstract Title:  Ginsenoside Rd attenuated hyperglycemia via Akt pathway and modulated gut microbiota in streptozotocin-induced diabetic rats. Abstract:  Ginsenoside Rd is a protopanaxadiol abundant in Panax ginseng and Panax notoginseng. It has been reported that ginsenoside Rd possesses various health benefits, such as anti-diabetic, anti-tumor and anti-inflammatory. This work explored the effects of ginsenoside Rd on hyperglycemia and gut microbiota in streptozotocin-induced diabetic rats. Results showed that 5-week ginsenoside Rd (20 mg/kg) treatment significantly improved hyperglycemia in diabetic rats. Besides, ginsenoside Rd promoted glycogen synthesis via activating Akt pathway. It also inhibited hepatic gluconeogenesis, which was associated with inhibiting phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. We further found that ginsenoside Rd treatment increased the diversity of gut microbiota, increased the abundance of beneficial bacteria, such as,and, and reduced the abundance of conditional pathogenic bacteria. These results indicated that ginsenoside Rd has the potential for diabetic intervention.

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PMID:  RSC Adv. 2023 Apr 3 ;13(16):11037-11043. Epub 2023 Apr 6. PMID: 37033442 Abstract Title:  Discovery of nontriterpenoids from the rot roots ofwith cytotoxicity and their molecular docking study and experimental validation. Abstract:  () is a well-known traditional Chinese medicine, with dammarane-type triterpenoid saponins characterized as major component and active ingredients, together with amino acids, flavonoids, polysaccharides, and polyacetylenes. The roots ofare susceptible to root rot disease, which causes a huge loss and changes in the chemical components of this precious resource. In this study, sub-fractions of rotroot extracts were preliminarily found to have admirable cytotoxicity on two human cancer cells. Further bioassay-guided isolation discovered nine new non-triterpenoids, including two novel-methylacetamido-1-oxotetrahydropyrimidine alkaloids (1, 2), five 2-furanones or 2-pyranones (3-7), and two polyacetylenic alcohols (8, 9). Their structures were illuminated by extensive spectroscopic data, calculated ECD, and X-ray diffraction analysis. Among them, 3-7 were considered to be transformed from panaxatriol through the intermediates (8, 9). The new alkaloids (1, 2) displayed noteworthy cytotoxicity against five human cancer cells with ICvalues ranging from 14 to 24M.target prediction and molecular docking studies showed that 1 and 2 may interact with EGFR, and were verified by the experimental inhibitory effect on EGFR tyrosine kinase.

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PMID:  Zhongguo Zhong Yao Za Zhi. 2023 Mar ;48(5):1319-1329. PMID: 37005816 Abstract Title:  [Effects of total ginsenosides from Panax ginseng stems and leaves on gut microbiota and short-chain fatty acids metabolism in acute lung injury mice]. Abstract:  This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice. Sixty male C57BL/6J mice were randomly divided into a control group, a model group, the total ginsenosides from P. ginseng stems and leaves normal administration group(61.65 mgkg~(-1)), and low-, medium-, and high-dose total ginsenosides from P. ginseng stems and leaves groups(15.412 5, 30.825, and 61.65 mgkg~(-1)). Mice were administered for seven continuous days before modeling. Twenty-four hours after modeling, mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio. The number of inflammatory cells in bronchoalveolar lavage fluid(BALF) was detected. The levels of interleukin-1(IL-1), interleukin-6(IL-6), and tumor necrosis factor-(TNF-) in BALF were detected. The mRNA expression levels of IL-1, IL-6, and TNF-, and the levels of myeloperoxidase(MPO), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in lung tissues were determined. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in lung tissues. The gut microbiota was detected by 16S rRNA sequencing, and gas chromatography-mass spectrometry(GC-MS) was applied to detect the content of short-chain fatty acids(SCFAs) in se-rum. The results showed that the total ginsenosides from P. ginseng stems and leaves could reduce lung index, lung wet/dry ratio, and lung damage in LPS-induced ALI mice, decrease the number of inflammatory cells and levels of inflammatory factors in BALF, inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues, and potentiate the activity of GSH-Px and SOD in lung tissues. Furthermore, they could also reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Lachnospiraceae and Muribaculaceae, decrease the relative abundance of Prevotellaceae, and enhance the content of SCFAs(acetic acid, propionic acid, and butyric acid) in serum. This study suggested that the total ginsenosides from P. ginseng stems and leaves could improve lung edema, inflammatory response, and oxidative stress in ALI mice by regulating gut microbiota and SCFAs metabolism.

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PMID:  Eur J Pharmacol. 2023 May 15 ;947:175676. Epub 2023 Mar 30. PMID: 37001580 Abstract Title:  Ginsenoside Rb1 promotes the activation of PPARpathway via inhibiting FADD to ameliorate heart failure. Abstract:  PURPOSE: Ginsenoside Rb1 (GRb1), a dammarane-type triterpene saponin compound mainly distributed in ginseng (Panax ginseng), has been demonstrated to ameliorate cardiovascular diseases. However, it remains unclear whether GRb1 alleviates heart failure (HF) by maintaining cardiac energy metabolism balance. Therefore, this work aimed to investigate the cardiac benefits of GRb1 against cardiac energy deficit and explore its mechanism of action.METHODS AND RESULTS: Isoproterenol (ISO) induced HF Sprague-Dawley rats were administrated with GRb1 or fenofibrate for 6 weeks. ISO-induced primary neonatal rat cardiomyocytes (NRCMs) were used as the in vitro model. In vivo, GRb1 significantly improved the structural and metabolic disorder, as demonstrated by the restoration of cardiac function, inhibition of cardiac hypertrophy and fibrosis, and increased adenosine triphosphate (ATP) generation. In vitro, GRb1 effectively protected mitochondrial function and scavenged excessive reactive oxygen species. Moreover, in ISO-induced NRCMs, GRb1 significantly inhibited the abnormal upregulation of Fas-associated death domain (FADD), promoted transcriptional activation of peroxisome proliferator-activated receptor-alpha (PPAR), improved the aberrant expression of cardiac energy metabolism-related enzymes and cardiac fatty acid oxidation, and subsequently increased the synthesis of ATP. Noticeably, GRb1 could inhibit the increased binding between FADD and PPAR, which contributed to the activation of PPAR. Furthermore, GRb1 strengthened the thermal stabilization of FADD and might bind to FADD directly.CONCLUSIONS: Collectively, it's part of the in-depth mechanism of GRb1's cardio-protection that GRb1 could directly bind to FADD and counteract its negative role in the transcription of PPARthus ameliorating cardiac energy derangement and HF.

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PMID:  J Microbiol Biotechnol. 2023 Jun 28 ;33(6):840-847. Epub 2023 Mar 30. PMID: 36994619 Abstract Title:  Korean Ginseng Berry Polysaccharide Enhances Immunomodulation Activities of Peritoneal Macrophages in Mice with Cyclophosphamide-Induced Immunosuppression. Abstract:  Korean ginseng (C. A. Meyer), a member of the Araliaceae family, is known as a traditional medicinal plant to have a wide range of health properties. Polysaccharides constitute a major component of Korean ginseng, and its berries exhibit immune-modulating properties. The purpose of this study was to investigate the immune effects of crude polysaccharide (GBPC) extracted from Korean ginseng berry on peritoneal macrophages in mice with cyclophosphamide (CY)- induced immunosuppression. BALB/c mice were divided into eight groups: normal control, normal control + CY, levamisole + CY, ginseng + CY, and four concentrations of 50, 100, 250, and 500mg/kg BW/day of GBPC + CY. Mice were orally administered with samples for 10 days. Immunosuppression was established by treating mice with CY (80 mg/kg BW/day) through intraperitoneal injection on days 4 to 6. The immune function of peritoneal macrophages was then evaluated. Oral administration of 500mg/kg BW/day GBPC resulted in proliferation, NO production, and phagocytosis at 100%, 88%, and 91%, respectively, close to the levels of the normal group (100%) of peritoneal macrophages. In CY-treated mice, GBPC of 50-500 mg/kg BW/day also dose-dependently stimulated the proliferation, NO production, and phagocytosis at 56-100%, 47-88%, and 53-91%, respectively, with expression levels of immune-associated genes, such as,,,, and, of about 0.32 to 2.87-fold, compared to those in the CY group. GBPC could be a potential immunomodulatory material to control peritoneal macrophages under an immunosuppressive condition.

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PMID:  Plants (Basel). 2023 Mar 18 ;12(6). Epub 2023 Mar 18. PMID: 36987052 Abstract Title:  Nootropic Herbs, Shrubs, and Trees as Potential Cognitive Enhancers. Abstract:  Plant-based nootropics are a diverse group of natural drugs that can improve cognitive abilities through various physiological mechanisms, especially in cases where these functions are weakened or impaired. In many cases, the nootropics enhance erythrocyte plasticity and inhibit aggregation, which improves the blood's rheological properties and increases its flow to the brain. Many of these formulations possess antioxidant activity that protects brain tissue from neurotoxicity and improves the brain's oxygen supply. They can induce the synthesis of neuronal proteins, nucleic acids, and phospholipids for constructing and repairing neurohormonal membranes. These natural compounds can potentially be present in a great variety of herbs, shrubs, and even some trees and vines. The plant species reviewed here were selected based on the availability of verifiable experimental data and clinical trials investigating potential nootropic effects. Original research articles, relevant animal studies, meta-analyses, systematic reviews, and clinical trials were included in this review. Selected representatives of this heterogeneous group included(L.) Wettst.,(L.) Urban,(Rupr.&Maxim.) Maxim.,L.,Walp.,C.A. Meyer,Kunth,L.,(Turcz.) Baill., and(L.) Dunal. The species are depicted and described, together with their active components and nootropic effects, and evidence of their efficacy is presented. The study provides brief descriptions of the representative species, their occurrence, history, and the chemical composition of the principle medicinal compounds, with uses, indications, experimental treatments, dosages, possible side effects, and contraindications. Most plant nootropics must be taken at optimal doses for extended periods before measurable improvement occurs, but they are generally very well tolerated. Their psychoactive properties are not produced by a single molecule but by a synergistic combination of several compounds. The available data suggest that including extracts from these plants in medicinal products to treat cognitive disorders can have substantial potential therapeutic benefits.

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PMID:  Life (Basel). 2022 Dec 22 ;13(1). Epub 2022 Dec 22. PMID: 36675981 Abstract Title:  Dysbiotic Gut Microbiota Modulation by Aronia Fruits Extract Administration. Abstract:  The administration of chokeberry extract in vitro in the GIS1 system was evaluated for the modulation capacity of the dysbiotic pattern resulting from the consumption of stevia. The microbial pattern determined by molecular method, the metabolomic one (fatty acids), the evolution of the antioxidant status, and the cytotoxic effect were determined comparatively for six months. This study presented for the first time that Aronia extract has a strong antimicrobial effect but also a presence of new organic acids that can be used as a biomarker. The functional supplement had the impact of a gradual increase in antioxidant status (DPPH scavenging activity) for up to three months and a subsequent decrease correlated with the reduction of the microbial load (especially for Enterobacteriaceae). The effect on metabolomic activity was specific, with butyric acid being generally unaffected (0.6-0.8 mg/mL) by the antimicrobial effect manifested after three months of administration. The pH was strongly acidic, corresponding to the constant presence of maximum values for acetic and lactic acid. The non-selective elimination of a part of the microbiota could also be correlated with a decrease in metabolomic efficiency. The results in the GIS1 system indicated for the first time that the controlled use of this extract had a pronounced antimicrobial and cytotoxic effect. This has helped to correct the dysbiotic pattern that results after the long-term use of sweeteners based on an increase of 0.2 log UFC/mL for favorable strains.

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PMID:  Phytomedicine. 2023 Jul ;115:154832. Epub 2023 Apr 18. PMID: 37121059 Abstract Title:  Flavonoids from Seabuckthorn (Hippophae rhamnoides L.) mimic neurotrophic functions in inducing neurite outgrowth in cultured neurons: Signaling via PI3K/Akt and ERK pathways. Abstract:  BACKGROUND: Various brain disorders, including neurodegenerative diseases and major depressive disorders, threaten an increasing number of patients. Seabuckthorn, a fruit from Hippophae rhamnoides L., is an example of "medicine food homology". The fruit has enriched flavonoids that reported to have benefits in treating cognitive disorders. However, the studies on potential functions of Seabuckthorn and/or its flavonoid-enriched fraction in treating neurodegenerative disorders are limited.PURPOSE: This study aimed to determine the ability and mechanism of the flavonoid-enriched fraction of Seabuckthorn (named as SBF) in mimicking the neurotrophic functions in inducing neurite outgrowth of cultured neurons.METHODS: Cultured PC12 cell line, SH-SY5Y cell line and primary neurons (cortical and hippocampal neurons isolated from E17-19 SD rat embryos) were the employed models to evaluate SBF in inducing neurite outgrowth by comparing to the effects of NGF and BDNF. Immuno-fluorescence staining was applied to identify the morphological change during the neuronal differentiation. Luciferase assay was utilized for analyzing the transcriptional regulation of neurofilaments and cAMP/CREB-mediated gene. Western blot assay was conducted to demonstrate the expressions of neurofilaments and phosphorylated proteins.RESULTS: The application of SBF induced neuronal cell differentiation, and this differentiating activation was blocked by the inhibitors of PI3K/Akt and ERK pathways. Additionally, SBF showed synergy with neurotrophic factors in stimulating the neurite outgrowth of cultured neurons. Moreover, the major flavonoids within SBF, i.e., isorhamnetin, quercetin and kaempferol, could account for the neurotrophic activities of SBF.CONCLUSION: Seabuckthorn flavonoids mimicked neurotrophic functions in inducing neuronal cell differentiation via activating PI3K/Akt and ERK pathways. The results suggest the beneficial functions of Seabuckthorn as a potential health food supplement in treating various brain disorders, e.g., neurodegenerative diseases.

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PMID:  Front Nutr. 2023 ;10:1136590. Epub 2023 Feb 9. PMID: 36845055 Abstract Title:  Prediction of active marker of seabuckthorn polysaccharides for prevention and treatment of cervical cancer and mechanism study. Abstract:  OBJECTIVE: To predict the target of Seabuckthorn polysaccharides in the prevention and treatment of cervical cancer, and to explore its multi-target and multi-pathway mechanism.METHODS: Using the Swisstarget database, a total of 61 potential targets of polysaccharide active components were obtained. Cervical cancer related targets were obtained from the GeneCards database. The correlation score was greater than 5 targets for 2727; 15 intersection targets of active ingredients and disease were obtained by Venn diagram. Cytoscape3.6.0 software was used to construct the Polysaccharide composition-Target-Disease Network and Protein-Protein Interaction Networks (PPI). Cytoscape3.6.0 software was used for visualization and network topology analysis to obtain core targets. Kyoto encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were analyzed using Metascape database. SailVina and PyMOL software were used for molecular docking to verify binding strength.RESULTS: A total of 15 core targets were obtained for cervical cancer. These targets are significantly enriched in HIF-1 signaling pathway, Galactose metabolism, EGFR tyrosine kinase inhibitor resistance, growth factor receptor binding, carbohydrate binding, protein homodimerization activity and other GO and KEGG entries; Molecular docking showed that ADA and GLB1 were well bound to Glucose, D-Mannose, and Galactose.CONCLUSION: The effect of seabuckthorn polysaccharides on the prevention and treatment of cervical cancer is characterized by multi-component, multi-target and multi-pathway, which provides scientific basis for further research on the activity of seabuckthorn polysaccharides.

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PMID:  Antioxidants (Basel). 2023 Apr 12 ;12(4). Epub 2023 Apr 12. PMID: 37107288 Abstract Title:  Total Phenolic and Total Flavonoid Content, Individual Phenolic Compounds and Antioxidant Activity in Sweet Rowanberry Cultivars. Abstract:  Sweet rowanberry and its cultivars represent a less-known fruit species with significant antioxidant activity, mostly promoted by polyphenolic compounds. This paper examined sevencultivars and evaluated their total polyphenolic and flavonoid content, as well as the content of individual polyphenolic compounds from the group of phenolic acids and flavonoids. It also determined their antioxidant activity using DPPH, ACW and ACL. Furthermore, to reflect the distribution of the contribution to antioxidant activity, correlations between antioxidant activity and the contents of ascorbic acid, vitamin E and individual phenolic compounds were established. The highest total phenolic content of 8307.4 mg kgwas determined in 'Granatina', with the main contribution of phenolic acid content of 7001.7 mg kgand a significantly lower total flavonoid content of 1304.6 mg kg. Flavanols represented the most abundant group of flavonoids, with catechin being the second most frequent flavanol with the highest content of 633.67 mg kgin 'Granatina'. Flavonols were represented by rutin and quercetin. 'Businka' displayed a significant vitamin E content of 4.77 mg kg, and 'Alaja Krupnaja' had the highest vitamin C level of 7.89 g kg. These results emphasize their potential health and nutritional benefits and, thus, their promising and valuable role in the food processing industry.

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PMID:  J Integr Neurosci. 2023 Feb 10 ;22(2):26. PMID: 36992594 Abstract Title:  Therapeutic Treatment with PycnogenolAttenuates Ischemic Brain Injury in Gerbils Focusing on Cognitive Impairment, Neuronal Death, BBB Leakage and Neuroinflammation in the Hippocampus. Abstract:  BACKGROUND: A gerbil model of ischemia and reperfusion (IR) injury in the forebrain has been developed for studies on mechanisms, prevention and therapeutic strategies of IR injury in the forebrain. Pycnogenol(PYC), a standardized extract of French maritime pine tree (Aiton) has been exploited as an additive for dietary supplement. In the present study, we investigated the neuroprotective effects of post-treatment with PYC and its therapeutic mechanisms in gerbils.METHODS: The gerbils were given sham and IR operation and intraperitoneally injected with vehicle and Pycnogenol(25, 50 and 100 mg/kg, respectively) immediately, at 24 hours and 48 hours after sham and IR operation. Through 8-arm radial maze test and passive avoidance test, each spatial memory and short-term memory function was assessed. To examine the neuroprotection of Pycnogenol, we conducted cresyl violet staining, immunohistochemistry for neuronal nuclei, and Fluoro-Jade B histofluorescence. Moreover, we carried out immunohistochemistry for immunoglobulin G (IgG) to investigate blood-brain barrier (BBB) leakage and interleukin-1(IL-1) to examine change in pro-inflammatory cytokine.RESULTS: We found that IR-induced memory deficits were significantly ameliorated when 100 mg/kg Pycnogenolwas treated. In addition, treatment with 100 mg/kg Pycnogenol, not 25 mg/kg nor 50 mg/kg, conferred neuroprotective effect against IR injury. For its mechanisms, we found that 100 mg/kg Pycnogenolsignificantly reduced BBB leakage and inhibited the expression of IL-1.CONCLUSIONS: Therapeutic treatment (post-treatment) with Pycnogenolafter IR effectively attenuated ischemic brain injury in gerbils. Based on these results, we suggest that PYC can be employed as an important material for ischemic drugs.

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PMID:  BMC Complement Med Ther. 2023 Apr 13 ;23(1):117. Epub 2023 Apr 13. PMID: 37055744 Abstract Title:  The neuroprotective effects of the combined extract of mulberry fruit and mulberry leaf against hydrogen peroxide-induced cytotoxicity in SH-SY5Y Cells. Abstract:  The prevalence of dementia is increasing, and most of the causes are related to neuronal cell death. Unfortunately, no effective strategy is available for protecting against this condition. Based on the use of the synergistic concept together with the positive modulation effect of both mulberry fruit and mulberry leaf on dementia, we hypothesized that the combined extract of mulberry fruit and mulberry leaf (MFML) should mitigate neuronal cell death. Neuronal cell damage was induced in SH-SY5Y cells by exposure to hydrogen peroxide at a dose of 200 M. SH-SY5Y cells were given MFML at doses of 62.5 and 125 g/mL before induced cytotoxicity. Then, the cell viability was determined via MTT assay, and the possible underlying mechanisms were investigated via the alterations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nuclear factor-B (NF-B), and tumor necrosis factor-alpha (TNF-), together with apoptotic factors including (B-cell lymphoma 2) BCL2, Casapase-3 and Caspase-9. The results showed that MFML significantly enhanced cell viability. It also significantly decreased MDA level, NF-B, TNF-, Casapase-3, Caspase-9, but increased SOD, GSH-Px and BCL2. These data demonstrated the neuroprotective effect of MFML. The possible underlying mechanisms might occur partly via the improvement of the inappropriate apoptotic mechanisms via BCL2, Casapase-3 and Caspase-9 together with the decrease in neurodegeneration induced by the reduction of inflammation and oxidative stress. In conclusion, MFML is a potential neuroprotectant candidate against neuronal cell injury. However, toxicity, animal studies, and clinical trials are essential to confirm these benefits.

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PMID:  J Ethnopharmacol. 2023 Sep 15 ;313:116475. Epub 2023 Apr 27. PMID: 37120060 Abstract Title:  Mulberry extract ameliorates T2DM-related symptoms via AMPK pathway in STZ-HFD-induced C57BL/6J mice. Abstract:  ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) is not only a tasty food but also a beneficial medicinal substance that has been historically used to treat diabetes, as recorded in Tang Ben Cao. Recent research on animal models has shown that the ethyl acetate extract of Morus alba L. fruits (EMF) has hypoglycemic and hypolipidemic properties. However, there is a lack of documentation on the specific mechanisms through which EMF exerts its hypoglycemic effects.OBJECTIVE OF THE STUDY: This study aimed to investigate the impact of EMF on L6 cells and C57/BL6J mice and to elucidate the potential mechanisms underlying its effects. The findings of this study can contribute to the existing evidence for the application of EMF as a therapeutic drug or dietary supplement in the management of type 2 diabetes mellitus (T2DM).MATERIALS AND METHODS: The UPLC-Q-TOF-MS technique was utilized to gather MS data. Masslynx 4.1 software in conjunction with the SciFinder database and other relevant references were used to analyze and identify the chemical composition of EMF. A series of in vitro investigations including MTT assay, glucose uptake assay and Western blot analysis were performed using an L6 cell model stably expressing IRAP-mOrange after EMF treatment. In vivo investigations were performed on a STZ-HFD co-induced T2DM mouse model, which included assessments of body composition, biochemical tests, histopathological analysis, and Western blot analysis.RESULTS: MTT results revealed that EMF had no toxic effects on the cells at various concentrations. When EMF was administered to L6 cells, there was an increase in glucose transporter type 4 (GLUT4) translocation activity and a significant dose-dependent enhancement of glucose uptake by L6 myotubes. EMF treatment led to a marked increase in P-AMPK levels and GLUT4 expression in the cells, but these effects were reversed by an AMPK inhibitor (Compound C). In diabetic mice with STZ-HFD-induced diabetes, EMF treatment improved oral glucose tolerance, hyperglycemia, and hyperinsulinemia. Furthermore, EMF supplementation significantly reduced insulin resistance (IR) in diabetic mice, as evaluated using a steady-state model of the insulin resistance index. Histopathological sections demonstrated that acute EMF treatment reduced hepatic steatosis, pancreatic damage, and adipocyte hypertrophy. Western blot analysis demonstrated that EMF treatment also reduced abnormally high PPARexpression, elevated the level of p-AMPK and p-ACC, and augmented the abundance of GLUT4 in insulin-sensitive peripheral tissues.SUMMARY: The results suggest tha...

PMID:  Antioxidants (Basel). 2023 Apr 21 ;12(4). Epub 2023 Apr 21. PMID: 37107352 Abstract Title:  The Prebiotic Effects of an Extract with Antioxidant Properties fromL. Contribute to Ameliorate High-Fat Diet-Induced Obesity in Mice. Abstract:  Obesity is a global health issue, in which modifications in gut microbiota composition have a key role. Different therapeutic strategies are being developed in combination with diet and exercise, including the use of plant extracts, such as those obtained fromL. leaves. Recent studies have revealed their anti-inflammatory and antioxidant properties. The aim of the present work was to evaluate whether the beneficial effects ofL. leaf extract in high-fat diet-induced obesity in mice is correlated with its impact on gut microbiota. The extract reduced body weight gain and attenuated lipid accumulation, as well as increased glucose sensitivity. These effects were associated with an amelioration of the obesity-associated inflammatory status, most probably due to the described antioxidant properties of the extract. Moreover,L. leaf extract mitigated gut dysbiosis, which was evidenced by the restoration of the/ratio and the decrease in plasma lipopolysaccharide (LPS) levels. Specifically, the extract administration reducedand increasedabundance, these effects being correlated with the beneficial effects exerted by the extract on the obesity-associated inflammation. In conclusion, anti-obesogenic effects ofL. leaf extract may be mediated through the amelioration of gut dysbiosis.

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PMID:  Phytomedicine. 2023 Jun ;114:154765. Epub 2023 Mar 16. PMID: 37004403 Abstract Title:  Morusinol extracted from Morus alba induces cell cycle arrest and apoptosis via inhibition of DNA damage response in melanoma by CHK1 degradation through the ubiquitin-proteasome pathway. Abstract:  BACKGROUD: Flavonoids have a variety of biological activities, such as anti-inflammation, anti-tumor, anti-thrombosis and so on. Morusinol, as a novel isoprene flavonoid extracted from Morus alba root barks, has the effects of anti-arterial thrombosis and anti-inflammatory in previous studies. However, the anti-cancer mechanism of morusinol remains unclear.PURPOSE: In present study, we mainly studied the anti-tumor effect of morusinol and its mode of action in melanoma.METHODS: The anti-cancer effect of morusinol on melanoma were evaluated by using the MTT, EdU, plate clone formation and soft agar assay. Flow cytometry was used for detecting cell cycle and apoptosis. The-H2AX immunofluorescence and the alkaline comet assay were used to detect DNA damage and the Western blotting analysis was used to investigate the expressions of DNA-damage related proteins. Ubiquitination and turnover of CHK1 were also detected by using the immunoprecipitation assay. The cell line-derived xenograft (CDX) mouse models were used in vivo to evaluate the effect of morusinol on tumorigenicity.RESULTS: We demonstrated that morusinol not only had the ability to inhibit cell proliferation, but also induced cell cycle arrest at G0/G1 phase, caspase-dependent apoptosis and DNA damage in human melanoma cells. In addition, morusinol effectively inhibited the growth of melanoma xenografts in vivo. More strikingly, CHK1, which played an important role in maintaining the integrity of cell cycle, genomic stability and cell viability, was down-regulated in a dose- and time-dependent manner after morusinol treatment. Further research showed that CHK1 was degraded by the ubiquitin-proteasome pathway. Whereafter, morusinol-induced cell cycle arrest, apoptosis and DNA damage were partially salvaged by overexpressing CHK1 in melanoma cell lines. Herein, further experiments demonstrated that morusinol increased the sensitivity of dacarbazine (DTIC) to chemotherapy for melanoma in vitro and in vivo.CONCLUSION: Morusinol induces CHK1 degradation through the ubiquitin-proteasome pathway, thereby inducing cell cycle arrest, apoptosis and DNA damage response in melanoma. Our study firstly provided a theoretical basis for morusinol to be a candidate drug for clinical treatment of cancer, such as melanoma, alone or combinated with dacarbazine.

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PMID:  Metab Brain Dis. 2023 Jun ;38(5):1657-1669. Epub 2023 Mar 22. PMID: 36947332 Abstract Title:  Morus alba fruit diet ameliorates cognitive deficit in mouse model of streptozotocin-induced memory impairment. Abstract:  Mounting evidence shows that dietary intake of fruits with polyphenols is beneficial to improve impaired memory functions. This study explored the preventive as well as therapeutic effects of diet enriched with Morus alba fruits extract (DEMA) in streptozotocin (STZ) induced mouse model of memory impairment. The study consisted of two facets: one aspect consisted of pretreatment of animals with DEMA for two weeks followed by STZ (i.c.v) intervention and the second phase involved induction of dementia with STZ (i.c.v) followed by treatment with DEMA for 14 days. Cognitive functions of animals were measured by Morris Water Maze test and to delineate the associated mechanism of action, brain biochemical estimations (acetyl-cholinesterase activity, myeloperoxidase activity, thiobarbituric acid reactive species, superoxide dismutase activity, reduced glutathione and nitrite/nitrate) and histopathological studies (haematoxylin and eosin staining) were performed. Pre- and post- treatment with DEMA significantly prevented and attenuated, respectively, the detrimental effects of STZ on mice brain. The results demonstrated that dietary modification, by incorporation of M. alba fruits, reduces the incidence and aids in treatment of memory disorder in mice by reducing central cholinergic activity, decreasing oxidative stress and preventing neurodegeneration.

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PMID:  Biomed Res Int. 2023 ;2023:9337763. Epub 2023 Apr 19. PMID: 37124934 Abstract Title:  Evaluation of the Anticancer Potential ofandMixture against Different Cancer Cell Lines: An In Vitro Evaluation. Abstract:  (M) and(O) mixture (MO2) extract was extracted using hexane (MO2H), chloroform (MO2C), ethyl acetate (MO2E), and methanol (MO2M) in a Soxhlet apparatus. The cytotoxicity was evaluated using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The ICvalues of the MO2C-treated cancer cells were 11.31g/mL (MDA-MB-231), 15.45g/mL (MCF-7), 18.9g/mL (HepG2), 26.33g/mL (Huh-7), 30.17g/mL (LoVo), and 36.76g/mL (HCT116). MO2C-treated cells showed cellular and nuclear morphological alterations like chromatin condensation and formation of apoptotic bodies as observed using light and fluorescent microscopy. The antioxidant and anti-inflammatory properties were investigated in vitro using 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and egg albumin denaturation assays. It was evident that the MO2M extract exhibited the highest antioxidant activity (18.13%), followed by the MO2E extract (12.25%), MO2C extract (9.380%), and MO2H extract (6.31%). The highest inhibition percentage of albumin denaturation was observed in MO2H (28.54%), followed by MO2M (4.32%) at 0.2 and 0.1mg/mL concentrations, respectively. The compounds identified using gas chromatography-mass spectrometry (GC-MS) analysis for MO2C extract were-trans-bergamotene, germacrene D, selin-4,7(11)-diene, 2 tridecen-1-ol, and 2-decen-1-ol. The present study reveals that MO2C has promising anticancer activity and may serve as a potent polyherbal extract in cancer treatment.

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PMID:  Heliyon. 2023 Apr ;9(4):e14644. Epub 2023 Mar 23. PMID: 37064472 Abstract Title:  Phytochemical characterization, antioxidant activity and antihypertensive evaluation ofL. in l-NAME induced hypertensive rats and its correlation analysis. Abstract:  (basil) is an aromatic culinary herb that has shown a great potential in therapeutic world. It has many promising pharmacological activities that make it centre for investigations for many researchers. Current study has been planned to determine chemical constituents of basil leaves extracts and theirandantioxidant andantihypertensive potential. GC-MS studies of non-polar extracts showed presence of 75 compounds including monoterpenes, hydrocarbons, sesquiterpenes, triterpenes, phyto-sterols and phthalates. Higher percentages of fatty acids were also identified. The major compounds include linalool (7.65%), terpineol (1.42%),-cadinol (13.55%), methyl palmitate (14.24%), palmitic acid (14.31%), linolenic acid (1.30%) and methyl linolenate (17.72%). Electron spray ionization mass spectrometry ESI-HRMS/MS of the polar extracts revealed the presence of alkaloids, phenolic acid, amino acid, coumarin, lignin, flavanoid and terpene derivative. Total phenolic content and total flavonoid content were determined using spectrophotometric technique and calculated as gallic acid equivalents GAE/g dry weight and rutin equivalent RE/g of dry weight respectively. The highest phenolic content and flavonoid content were found in ethyl acetate extract 9.40 mg GAE/g and 15.9 mg RE/g of dry weight. All the extracts showed significant antioxidant activity in DPPH and ABTS cation decolorization assays. Dichloromethane extract possess the highest DPPH scavenging activity, i.e., 64.12%  0.23 at concentration of 4 mg/ml. Moreover instudies all the extracts showed prominent effect by inhibiting AAPS induce oxidation in Human erythrocytes being 69.24%  0.18 in dichloromethane extract, 64.44%  0.04 in ethyl acetate and 53.33%  0.09 in acetone extract. The methanol extract ofexhibited significant decrease in systolic blood pressure in l-Name induced hypertensive rats at the dose of 50 mg/kg for 28 days. Total phenolic content had a higher linear correlation (r = 0.678) with antihypertensive activity, with a level of significance 95% showing that phenolic compounds in the leaves of the plant has important role in inhibiting l -NAME induced hypertension while flavonoid compounds may play a key role in the antioxidant activities of the plant, through synergism. Conclusively,leaves with bioactive metabolites are a potential source for the development of antihypertensive drugs.

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PMID:  Chem Biodivers. 2023 May ;20(5):e202300017. Epub 2023 May 2. PMID: 37071473 Abstract Title:  Dose-Dependent Dual Effect of Morus nigra L. Extract on Urinary Parameters of Hypertensive Rats. Abstract:  This study investigated the diuretic and antiurolithic effects of the hydroalcoholic extract obtained from Morus nigra L. leaves (HEMN) in female hypertensive rats. The rats were treated orally with vehicle (VEH), hydrochlorothiazide (HCTZ), or HEMN. After 8 h, the urine was analyzed. Besides, the precipitation of calcium oxalate (CaOx) was induced in the urine. The HEMN, at a dose of 0.03mg/g, increased the volume of urine compared to the VEH-treated group and increased the urinary content of Cl, without altering the excretion of Naand K. Besides, HENM reduced the elimination of Cain the urine. On the other hand, at a dose of 0.1mg/g, it significantly reduced the volume of urine excreted, thus suggesting an antidiuretic effect dependent on the dose used. Similarly, HEMN at concentrations of 1 and 3mg/mL reduced CaOx crystals' formation in monohydrate and dihydrate forms. However, with the increase in the concentration of HEMN to 10mg/mL, a significant increase in the formation of CaOx crystals was found. In conclusion, M. nigra extract has a dose-dependent dual effect on urinary parameters, which may have a diuretic and antiurolithic effect at lower doses or the opposite effect at higher doses.

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PMID:  BMC Complement Med Ther. 2023 Apr 12 ;23(1):112. Epub 2023 Apr 12. PMID: 37046263 Abstract Title:  Polysaccharides extracted from mulberry fruits (Morus nigra L.): antioxidant effect of ameliorating HO-induced liver injury in HepG2 cells. Abstract:  BACKGROUND: Mori Fructus is an economical and readily available traditional Chinese medicine and food. Polysaccharides in Mori Fructus have clear antioxidant activity and have been found to alleviate oxidative stress (OS)-induced liver damage in experimental studies. The mechanism of regulation of cellular antioxidant activity by mulberry polysaccharides has been suggested to be Nrf2, but it is not clear whether the Nrf2 pathway is mediated by activation of other targets, and the exact process of effects in hepatocytes has yet to be elucidated.METHODS: In this study, the basic characterization of total polysaccharides extracted from mulberry fruits (Morus nigra Linn.) was analyzed. A model of oxidative damage induced by HOin HepG2 cells was established. The levels of cellular oxidation-related markers, including ROS, SOD and Gpx, were then examined. Furthermore, Q-PCR and Western-blot were used to detect the expression of genes and proteins related to the PI3K/Akt-mediated Nrf2 signaling pathway.RESULTS: The results showed that a total mulberry polysaccharides (TMP) has a molecular weight of 57.5 kDa with a pyranose ring mainly composed of glucose (48.81%), galactose (22.79%) and mannose (18.2%). TMP reduced the accumulation of ROS in HepG2 cells after HOtreatment and modulated the activity of SOD and Gpx. Q-PCR and Western-blot showed that TMP could up-regulate the expression of p-PI3K, p-AKT, Nrf2, NQO1 and HO-1.CONCLUSIONS: This study demonstrates that TMP can reduce ROS accumulation in HO-treated HepG2 cells and restore cell viability by activating the PI3K/AKT-mediated Nrf2 pathway. TMP may be a potent antioxidant agent that could slow down oxidative damage to the liver.

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PMID:  Antioxidants (Basel). 2023 Feb 4 ;12(2). Epub 2023 Feb 4. PMID: 36829941 Abstract Title:  Comprehensive Analysis of Antioxidant and Hepatoprotective Properties ofL. Abstract:  The framework of this study was a comprehensive investigation ofL. extracts, with the aim to establish the correlation between chemical composition and antioxidant/hepatoprotective activity of a series of black mulberry extracts obtained from aerial parts of the plant. Black mulberry leaf (MLEE), bark (MBEE), juice (MJ) and fresh fruit (MFEE) extracts were obtained using the conventional Soxhlet extraction, while the supercritical COextraction procedure was employed for preparation of the seed oil (MSO). Analysis of the chemical composition was performed using spectrophotometric, HPLC and GC methods. For the evaluation of antioxidant activity, in vitro FRAP and DPPH assays were applied. In Haan strain NMRI mice with streptozotocin-induced oxidative stress, in vivo antioxidant activity and liver tissue integrity were examined. The content of polyphenolic compounds was the highest in MBEE (68.30.7 mgGAE/g) with the most abundant compounds being polyphenolic acids, followed by MLEE (23.40.5 mgGAE/g) with the flavonoids isoquercetin and rutin being present in a significant amount. An analysis of MSO revealed a high content of-linoleic acid. The highest antioxidant activity in vitro (FRAP and DPPH) was observed for MLEE, MBEE and MSO. Beneficial effects were confirmed in vivo, with lower values of hepatosomatic index, potentiation of the activity of the enzymes superoxide dismutase and catalase, a lower rate of lipid peroxidation and reduced positivity for the P450 enzyme in animals treated with MLEE, MBEE and MSO. Black mulberry leaf and bark extracts as well as seed oil exhibited significant antioxidant activity. Apart from the confirmed biological properties of the fruit and leaf extracts, the observed activities of black mulberry seed oil and bark extract imply its importance as a sustainable source of phytochemicals.

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PMID:  Plants (Basel). 2022 Nov 17 ;11(22). Epub 2022 Nov 17. PMID: 36432875 Abstract Title:  Hydroethanolic Extract of Morus nigra L. Leaves: A Dual PPAR-/Agonist with Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated RAW 264.7. Abstract:  Inhibition of systemic inflammation has been a beneficial strategy in treating several non-communicable diseases, which represent one of the major causes of mortality in the world. The Peroxisome Proliferator-Activated Receptors (PPAR) are interesting pharmacological targets, since they can act both through the metabolic and anti-inflammatory pathways.L. has flavonoids in its chemical composition with recognized anti-oxidant activity and often associated with anti-inflammatory activity. Therefore, this study aimed to evaluate the hydroethanolic extract ofleaves' ability to activate PPAR and promote anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated murine macrophage cells. The leaf extract was prepared by cold maceration, and the chemical profile was obtained by HPLC-DAD. Activation of PPARandwas evaluated by the luciferase reporter assay. The anti-inflammatory activity was assessed by measuring the reactive oxygen species (ROS), nitric oxide (NO), and Tumor Necrosis Factor-(TNF-) in RAW 264.7 cells after stimulation with LPS from. The HPLC-DAD analysis identified two major compounds: rutin and isoquercitrin. The extract showed agonist activity for the two types of PPAR,and, although its major compounds, rutin and isoquercitrin, did not significantly activate the receptors. In addition, the extract significantly reduced the production of ROS, NO, and TNF-. Treatment with the specific PPAR-antagonist, GW 6471, was able to partially block the anti-inflammatory effect caused by the extract.

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PMID:  J Agric Food Chem. 2022 Oct 5 ;70(39):12484-12501. Epub 2022 Sep 23. PMID: 36150176 Abstract Title:  Ameliorating Effect of the Total Flavonoids ofL. on Prediabetic Mice Based on Regulation of Inflammation and Insulin Sensitization. Abstract:  Prediabetes is a critical stage characterized by insulin resistance.L., an edible plant, is widely used in food and nutritive supplements and exhibits various pharmacological activities; however, its therapeutic effects and mechanisms on prediabetes have rarely been reported. In this research, the major components of total flavonoids ofL. (TFM) were identified, and TFM treatment was found to reduce prediabetes progressing to type 2 diabetes mellitus (T2DM) from 93.75 to 18.75%. The microbiota and next-generation sequencing combined with western blotting in vivo and in vitro demonstrated that TFM and its components ameliorated insulin resistance mediated by the suppressor of cytokine signaling and protein tyrosine phosphatase 1B, which benefited by maintaining intestinal homeostasis and restraining plasma levels of inflammatory factors. This study confirmed the T2DM prevention effect of TFM and revealed the underlying mechanism, setting the stage for the design of functional foods for diabetes prevention.

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Opening comments to the general public to ask a question, in sincerity: what changed the minds of society's former First Amendment advocates?

Originally published on www.racket.news by Matt Taibbi

Opening comments to the general public to ask a question, in sincerity: what changed the minds of society's former First Amendment advocates?

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