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.

read more

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 (

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

...

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.

read more

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.

read more

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.

read more

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.

...

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.

read more

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.

read more

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

read more

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.

...

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 (

read more

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."

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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.

read more

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?

read more

PMID:  Evid Based Complement Alternat Med. 2023 ;2023:1265103. Epub 2023 Apr 20. PMID: 37123084 Abstract Title:  Vasorelaxant Effect of MoroccanThreshing Residues on Rat Mesenteric Arterial Bed is Endothelium and Muscarinic Receptors Dependent. Abstract:  INTRODUCTION: Ethanolic fraction of Moroccanthreshing residues (EFCS) was evaluated for its vasorelaxant activity. The current work aims to identify the active metabolites in the ethanolic fraction of the EFCS and illustrate their mechanism of action.METHODS: Free radical scavenging capacity of EFCS was assessed using DPPH method. The EFCS vasodilation activities in phenylephrine-precontracted isolated rat mesenteric arterial beds were investigated in presence of L-NAME (nitric oxide synthase inhibitor), indomethacin (cyclooxygenase inhibitor), potassium channel blockers (namely tetraetylamonium, barium chloride, and glibenclamide), and atropine. Nitric oxide vascular release was measured by electron paramagnetic resonance (EPR) using a spin trap in rat aortic rings.RESULTS: EFCS induced dose-dependent vasorelaxation on mesenteric vascular bed. Incubation of the preparations with L-NAME, ODQ (a soluble guanylyl cyclase inhibitor), or potassium channel blockers reduced the fall of perfusion pressure caused by EFCS. Endothelial denudation or atropine abolished the EFCS's vasorelaxant effect, suggesting involvement of muscarinic receptors and endothelium-relaxing factors. The extract induced nitric oxide release in aortic rings in a similar manner as acetylcholine suggesting an effect of EFCS on the muscarinic receptor and the conductance arteries. Chemical investigation of EFCS identified potential active components namely apigenin and derivatives of luteolin skeleton and also additional components such as neophytadiene, squalene, and-sitosterol. In conclusion, the vasorelaxant effect of EFCS on rat mesenteric arterial bed, which is dependent of muscarinic receptor activation, nitric oxide, and EDHF, can account for potential therapeutic use against high blood pressure related cardiovascular diseases.

read more

PMID:  BMJ Support Palliat Care. 2023 May 2. Epub 2023 May 2. PMID: 37130724 Abstract Title:  Medical cannabis is effective for cancer-related pain: Quebec Cannabis Registry results. Abstract:  OBJECTIVES: To evaluate the safety and effectiveness of medical cannabis (MC) in reducing pain and concurrent medications in patients with cancer.METHODS: This study analysed data collected from patients with cancer who were part of the Quebec Cannabis Registry. Brief Pain Inventory (BPI), revised Edmonton Symptom Assessment System (ESAS-r) questionnaires, total medication burden (TMB) and morphine equivalent daily dose (MEDD) recorded at 3-month, 6-month, 9-month and 12-month follow-ups were compared with baseline values. Adverse events were also documented at each follow-up visit.RESULTS: This study included 358 patients with cancer. Thirteen out of 15 adverse events reported in 11 patients were not serious; 2 serious events (pneumonia and cardiovascular event) were considered unlikely related to MC. Statistically significant decreases were observed at 3-month, 6-month and 9-month follow-up for BPI worst pain (5.50.7 baseline, 3.60.7, 3.60.7, 3.60.8; p

read more

PMID:  NPJ Vaccines. 2023 May 2 ;8(1):64. Epub 2023 May 2. PMID: 37130882 Abstract Title:  Risk assessment of retinal vascular occlusion after COVID-19 vaccination. Abstract:  Coronavirus disease 2019 (COVID-19) vaccines are associated with several ocular manifestations. Emerging evidence has been reported; however, the causality between the two is debatable. We aimed to investigate the risk of retinal vascular occlusion after COVID-19 vaccination. This retrospective cohort study used the TriNetX global network and included individuals vaccinated with COVID-19 vaccines between January 2020 and December 2022. We excluded individuals with a history of retinal vascular occlusion or those who used any systemic medication that could potentially affect blood coagulation prior to vaccination. To compare the risk of retinal vascular occlusion, we employed multivariable-adjusted Cox proportional hazards models after performing a 1:1 propensity score matching between the vaccinated and unvaccinated cohorts. Individuals with COVID-19 vaccination had a higher risk of all forms of retinal vascular occlusion in 2 years after vaccination, with an overall hazard ratio of 2.19 (95% confidence interval 2.00-2.39). The cumulative incidence of retinal vascular occlusion was significantly higher in the vaccinated cohort compared to the unvaccinated cohort, 2 years and 12 weeks after vaccination. The risk of retinal vascular occlusion significantly increased during the first 2 weeks after vaccination and persisted for 12 weeks. Additionally, individuals with first and second dose of BNT162b2 and mRNA-1273 had significantly increased risk of retinal vascular occlusion 2 years following vaccination, while no disparity was detected between brand and dose of vaccines. This large multicenter study strengthens the findings of previous cases. Retinal vascular occlusion may not be a coincidental finding after COVID-19 vaccination.

read more

PMID:  Surg Case Rep. 2023 Apr 25 ;9(1):64. Epub 2023 Apr 25. PMID: 37095273 Abstract Title:  Spontaneous regression of advanced transverse colon cancer with deficient mismatch repair: a case report. Abstract:  BACKGROUND: Spontaneous regression (SR) of cancer occurs in 1 in 60,000-100,000 patients. This phenomenon has been reported in almost all cancer types, most commonly neuroblastoma, renal cell carcinoma, malignant melanoma, and lymphoma/leukemia. However, SR in colorectal cancer (CRC) is extremely rare, particularly in advanced cases. Hence, this report describes a very rare case of spontaneous regression of advanced transverse colon cancer.CASE PRESENTATION: A 76-year-old female with anemia was diagnosed with a type II well-differentiated adenocarcinoma in the middle transverse colon. Two months later, a second colonoscopy examination was performed for preoperative marking, and it revealed tumor shrinkage and a shift to type 0-IIc morphology. Endoscopic tattooing was then performed, followed by a laparoscopic partial resection of the transverse colon with D3 lymph node dissection. However, the resected specimen contained no tumor, and colonoscopy showed no tumor remnants in the remaining colon. Histopathological examination revealed mucosal regeneration and a mucus nodule in between the submucosal and muscular layers, with no cancer cells detected. Immunohistochemical analysis revealed the loss of MutL homolog 1 (MLH1) and postmeiotic segregation increased 2 (PMS2) expression in the cancer cells of biopsied specimens, suggesting deficient mismatch repair (dMMR). The patient continues to be followed up until 6 years postoperatively, and no recurrence has been observed. In this study, we also reviewed similar reported cases of spontaneous regression of cancer involving dMMR.CONCLUSION: This study presents a rare case of spontaneous regression of advanced transverse colon cancer wherein dMMR is strongly involved. However, further accumulation of similar cases is needed to elucidate this phenomenon and to develop new treatment strategies for CRC.

read more

PMID:  Commun Biol. 2023 Apr 22 ;6(1):444. Epub 2023 Apr 22. PMID: 37087494 Abstract Title:  Spontaneous tumor regression mediated by human T cells in a humanized immune system mouse model. Abstract:  Immunodeficient mice reconstituted with a human immune system (HIS mice) give rise to human T cells, which make them an attractive system to study human immune responses to tumors. However, such HIS mice typically exhibit sub-optimal responses to immune challenges as well as fail to develop antigen-specific B or T cell memory. Here we report HIS mice mediate spontaneous regression of human B cell lymphoma Raji. Tumor regression was dependent on CD4+ and CD8+ T cell responses and resulted in T cell memory. The T cell memory elicited was mainly Raji-specific, however some level of cross-protection was also elicited to a related B cell lymphoma cell line Ramos. Single-cell RNAseq analysis indicated activation of CD8+ T cells in regressing Raji tumors as well as clonal expansion of specific T cell receptors (TCRs). Cloning of TCRs from Raji-infiltrating T cells into a Jurkat reporter cell line showed reactivity specific for Raji tumor cells. Overall, we report a platform for studying in vivo human T cell tumor immunity by highlighting spontaneous Raji tumor regression, clonal TCR expansion, and T cell memory in HIS mice.

read more

PMID:  J Transl Med. 2023 Apr 21 ;21(1):273. Epub 2023 Apr 21. PMID: 37085802 Abstract Title:  Spontaneous cancer remission after COVID-19: insights from the pandemic and their relevance for cancer treatment. Abstract:  Early in the COVID-19 pandemic, it emerged that the risk of severe outcomes was greater in patients with co-morbidities, including cancer. The huge effort undertaken to fight the pandemic, affects the management of cancer care, influencing their outcome. Despite the high fatality rate of COVID-19 disease in cancer patients, rare cases of temporary or prolonged clinical remission from cancers after SARS-CoV-2 infection have been reported. We have reviewed sixteen case reports of COVID-19 disease with spontaneous cancer reduction of progression. Fourteen cases of remission following viral infections and two after anti-SARS-CoV-2 vaccination. The immune response to COVID-19, may be implicated in both tumor regression, and progression. Specifically, we discuss potential mechanisms which include oncolytic and priming hypotheses, that may have contributed to the cancer regression in these cases and could be useful for future options in cancer treatment.

read more

PMID:  Antioxidants (Basel). 2023 Mar 28 ;12(4). Epub 2023 Mar 28. PMID: 37107196 Abstract Title:  Rutin Protects Fibroblasts from UVA Radiation through Stimulation of Nrf2 Pathway. Abstract:  This study explores the photoprotective effects of rutin, a bioflavonoid found in some vegetables and fruits, against UVA-induced damage in human skin fibroblasts. Our results show that rutin increases cell viability and reduces the high levels of ROS generated by photo-oxidative stress (1 and 2 h of UVA exposure). These effects are related to rutin's ability to modulate the Nrf2 transcriptional pathway. Interestingly, activation of the Nrf2 signaling pathway results in an increase in reduced glutathione and Bcl2/Bax ratio, and the subsequent protection of mitochondrial respiratory capacity. These results demonstrate how rutin may play a potentially cytoprotective role against UVA-induced skin damage through a purely antiapoptotic mechanism.

read more

PMID:  Antioxidants (Basel). 2023 Mar 3 ;12(3). Epub 2023 Mar 3. PMID: 36978887 Abstract Title:  Rutin Prevents Dexamethasone-Induced Muscle Loss in C2C12 Myotube and Mouse Model by Controlling FOXO3-Dependent Signaling. Abstract:  One of the causes of sarcopenia is that homeostasis between anabolism and catabolism breaks down due to muscle metabolism changes. Rutin has shown antioxidant and anti-inflammatory effects in various diseases, but there are few studies on the effect on muscle loss with aging. The effect of rutin on muscle loss was evaluated using dexamethasone-induced muscle loss C2C12 myoblast and mouse model. In the group treated with dexamethasone, the muscle weight of gastrocnemius (GA), tibialis anterior (TA), and extensor digitorum longus (EDL) in the mouse model were significantly decreased (

read more

PMID:  Biomolecules. 2023 Mar 20 ;13(3). Epub 2023 Mar 20. PMID: 36979499 Abstract Title:  Potential Treatment Options for Neuroblastoma with Polyphenols through Anti-Proliferative and Apoptotic Mechanisms. Abstract:  Neuroblastoma (NB) is an extracranial tumor of the peripheral nervous system arising from neural crest cells. It is the most common malignancy in infants and the most common extracranial solid tumor in children. The current treatment for high-risk NB involves chemotherapy and surgical resection followed by high-dose chemotherapy with autologous stem-cell rescue and radiation treatment. However, those with high-risk NB are susceptible to relapse and the long-term side effects of standard chemotherapy. Polyphenols, including the sub-class of flavonoids, contain more than one aromatic ring with hydroxyl groups. The literature demonstrates their utility in inducing the apoptosis of neuroblastoma cells, mostly in vitro and some in vivo. This review explores the use of various polyphenols outlined in primary studies, underlines the pathways involved in apoptotic activity, and discusses the dosage and delivery of these polyphenols. Primary studies were obtained from multiple databases with search the terms "neuroblastoma", "flavonoid", and "apoptosis". The in vitro studies showed that polyphenols exert an apoptotic effect on several NB cell lines. These polyphenols include apigenin, genistein, didymin, rutin, quercetin, curcumin, resveratrol, butein, bisphenols, and various plant extracts. The mechanisms of the therapeutic effects include calpain-dependent pathways, receptor-mediated apoptosis, and, notably, and most frequently, mitochondrial apoptosis pathways, including the mitochondrial proteins Bax and Bcl-2. Overall, polyphenols demonstrate potency in decreasing NB proliferation and inducing apoptosis, indicating significant potential for further in vivo research.

read more

PMID:  Med Oncol. 2023 Mar 27 ;40(5):131. Epub 2023 Mar 27. PMID: 36971893 Abstract Title:  Determination of Rutin's antitumoral effect on EAC solid tumor by AgNOR count and PI3K/AKT/mTOR signaling pathway. Abstract:  Rutin is one of the flavonoids found in fruits and vegetables. The PI3K/AKT/mTOR signaling pathway is critical for the life cycle at the cellular level. In current study, we purposed to demonstrate the antitumoral effect of rutin at different doses through the mTOR-signaling pathway and argyrophilic nucleolar regulatory region. EAC cells were injected subcutaneously into the experimental groups. 25 and 50 mg/kg Rutin were injected intraperitoneally to the animals with solid tumors for 14 days. Immunohistochemical, Real-time PCR and AgNOR analyzes were actualized on the taken tumors. When the rutin given groups and the tumor group were compared, the tumor size increase was detected to be statistically significant (p 

read more

PMID:  Pak J Pharm Sci. 2023 Jan ;36(1):217-221. PMID: 36967515 Abstract Title:  Rutin improves diabetes-induced muscle atrophy in mice. Abstract:  Muscle atrophy is a common complication in diabetes mellitus. Rutin has multiple biologic and therapeutic effects both in diabetic complications and muscle functions. However, no researches have implied prevention and treatment of rutin on muscle atrophy in diabetes mellitus. Our data demonstrated that rutin increased myocyte area and weight of gastrocnemius to promote muscular strength (p

read more

PMID:  Int J Biol Macromol. 2023 May 31 ;238:124151. Epub 2023 Mar 22. PMID: 36963546 Abstract Title:  Rutin impedes human low-density lipoprotein from non-enzymatic glycation: A mechanistic insight against diabetes-related disorders. Abstract:  Glycation of human low-density protein (LDL) has an essential contribution to cardiovascular diseases. Natural compounds like rutin have been extensively studied in preventing glycation-induced oxidative stress. This study examined rutin's anti-glycation potential with glycated LDL utilizing spectroscopic and in silico methods. Glycated LDL treated with rutin, showed around 80 % inhibition in advanced glycation end-product production. Carbonyl content and lipid peroxidation like assays were used to establish the development of oxidative stress. Rutin was seen to lower the generation of oxidative stress in a dose-dependent manner. Using thioflavin-T assay and electron microscopy, rutin was suggested to restore the structural disturbances in glycated LDL. Moreover, CD spectroscopy suggested reinstation of secondary structure of glycated LDL treated with rutin. Mechanistic insights between rutin and LDL were observed through spectroscopic measures. Molecular docking study confirmed the LDL-rutin binding with a binding energy of -10.0 kcal/mol. The rutin-LDL complex was revealed to be highly stable by molecular dynamics simulation, with RMSD, RMSF, Rg, SASA, and the secondary structure of LDL remaining essentially unchanged during the simulation period. Our study suggests that rutin possesses strong anti-glycating properties, which can be useful in therapeutics, as glycated LDL has an important role in atherosclerotic cardiovascular diseases.

read more

PMID:  Pharmaceuticals (Basel). 2023 Apr 17 ;16(4). Epub 2023 Apr 17. PMID: 37111362 Abstract Title:  The Role of Natural Flavonoids as Telomerase Inhibitors in Suppressing Cancer Growth. Abstract:  Cancer is a complex and multifaceted group of diseases characterized by the uncontrolled growth and spread of abnormal cells. While cancer can be challenging and life-altering, advances in research and development have led to the identification of new promising anti-cancer targets. Telomerase is one such target that is overexpressed in almost all cancer cells and plays a critical role in maintaining telomere length, which is essential for cell proliferation and survival. Inhibiting telomerase activity can lead to telomere shortening and eventual cell death, thus presenting itself as a potential target for cancer therapy. Naturally occurring flavonoids are a class of compounds that have already been shown to possess different biological properties, including the anti-cancer property. They are present in various everyday food sources and richly present in fruits, nuts, soybeans, vegetables, tea, wine, and berries, to name a few. Thus, these flavonoids could inhibit or deactivate telomerase expression in cancer cells by different mechanisms, which include inhibiting the expression of hTERT, mRNA, protein, and nuclear translocation, inhibiting the binding of transcription factors to hTERT promoters, and even telomere shortening. Numerous cell line studies and in vivo experiments have supported this hypothesis, and this development could serve as a vital and innovative therapeutic option for cancer. In this light, we aim to elucidate the role of telomerase as a potential anti-cancer target. Subsequently, we have illustrated that how commonly found natural flavonoids demonstrate their anti-cancer activity via telomerase inactivation in different cancer types, thus proving the potential of these naturally occurring flavonoids as useful therapeutic agents.

read more

PMID:  Nutrients. 2023 Apr 21 ;15(8). Epub 2023 Apr 21. PMID: 37111212 Abstract Title:  Epigallocatechin-3-Gallate Alleviates Liver Oxidative Damage Caused by Iron Overload in Mice through Inhibiting Ferroptosis. Abstract:  Ferroptosis, a form of regulated cell death, has been widely explored as a novel target for the treatment of diseases. The failure of the antioxidant system can induce ferroptosis. Epigallocatechin-3-Gallate (EGCG) is a natural antioxidant in tea; however, whether EGCG can regulate ferroptosis in the treatment of liver oxidative damage, as well as the exact molecular mechanism, is unknown. Here, we discovered that iron overload disturbed iron homeostasis in mice, leading to oxidative stress and damage in the liver by activating ferroptosis. However, EGCG supplementation alleviated the liver oxidative damage caused by iron overload by inhibiting ferroptosis. EGCG addition increased NRF2 and GPX4 expression and elevated antioxidant capacity in iron overload mice. EGCG administration attenuates iron metabolism disorders by upregulating FTH/L expression. Through these two mechanisms, EGCG can effectively inhibit iron overload-induced ferroptosis. Taken together, these findings suggest that EGCG is a potential ferroptosis suppressor, and may be a promising therapeutic agent for iron overload-induced liver disease.

read more

PMID:  Antioxidants (Basel). 2023 Apr 20 ;12(4). Epub 2023 Apr 20. PMID: 37107343 Abstract Title:  EGCG Attenuates CA1 Neuronal Death by Regulating GPx1, NF-B S536 Phosphorylation and Mitochondrial Dynamics in the Rat Hippocampus following Status Epilepticus. Abstract:  Epigallocatechin-3-gallate (EGCG) is an antioxidant that directly scavenges reactive oxygen species (ROS) and inhibits pro-oxidant enzymes. Although EGCG protects hippocampal neurons from status epilepticus (SE, a prolonged seizure activity), the underlying mechanisms are not fully understood. As the preservation of mitochondrial dynamics is essential for cell viability, it is noteworthy to elucidate the effects of EGCG on impaired mitochondrial dynamics and the related signaling pathways in SE-induced CA1 neuronal degeneration, which are yet unclear. In the present study, we found that EGCG attenuated SE-induced CA1 neuronal death, accompanied by glutathione peroxidase-1 (GPx1) induction. EGCG also abrogated mitochondrial hyperfusion in these neurons by the preservation of extracellular signal-regulated kinase 1/2 (ERK1/2)-dynamin-related protein 1 (DRP1)-mediated mitochondrial fission, independent of c-Jun-terminal kinase (JNK) activity. Furthermore, EGCG abolished SE-induced nuclear factor-B (NF-B) serine (S) 536 phosphorylation in CA1 neurons. ERK1/2 inhibition by U0126 diminished the effect of EGCG on neuroprotection and mitochondrial hyperfusion in response to SE without affecting GPx1 induction and NF-B S536 phosphorylation, indicating that the restoration of ERK1/2-DRP1-mediated fission may be required for the neuroprotective effects of EGCG against SE. Therefore, our findings suggest that EGCG may protect CA1 neurons from SE insults through GPx1-ERK1/2-DRP1 and GPx1-NF-B signaling pathways, respectively.

read more

PMID:  Cardiovasc Drugs Ther. 2023 Mar 31. Epub 2023 Mar 31. PMID: 37000367 Abstract Title:  Epigallocatechin-3-Gallate Inhibits Atrial Fibrosis and Reduces the Occurrence and Maintenance of Atrial Fibrillation and its Possible Mechanisms. Abstract:  BACKGROUND: Atrial fibrosis is one of the main causes of the onset and recurrence of atrial fibrillation (AF), for which there is no effective treatment. The aim of this study was to investigate the effect and mechanism of epigallocatechin-3-gallate (EGCG) on AF in rats.METHODS: The rat model of AF was established by rapid pacing induction after angiotensin-II (Ang-II) induced atrial fibrosis to verify the relationship between atrial fibrosis and the AF. The expression levels of TGF-/Smad3 pathway molecules and lysyl oxidase (LOX) in AF were detected. Subsequently, EGCG was used to intervene Ang-II-induced atrial fibrosis to explore the role of EGCG in the treatment of AF and its inhibitory mechanism on fibrosis. It was further verified that EGCG inhibited the production of collagen and the expression of LOX through the TGF-/Smad3 pathway at the cellular level.RESULTS: The results showed that the induction rate and maintenance time of AF in rats increased with the increase of the degree of atrial fibrosis. Meanwhile, the expressions of Col I, Col III, molecules related to TGF-/Smad3 pathway, and LOX increased significantly in the atrial tissues of rats in the Ang-II induced group. EGCG could reduce the occurrence and maintenance time of AF by inhibiting the degree of Ang-induced rat atrial fibrosis. Cell experiments confirmed that EGCG could reduce the synthesis of collagen and the expression of LOX in cardiac fibroblast induced by Ang-II. The possible mechanism is to down-regulate the expression of genes and proteins related to the TGF-/Smad3 pathway.CONCLUSION: EGCG could downregulate the expression levels of collagen and LOX by inhibiting the TGF-/Smad3 signaling pathway, alleviating Ang-II-induced atrial fibrosis, which in turn inhibited the occurrence and curtailed the duration of AF.

read more

PMID:  Pathogens. 2023 Mar 6 ;12(3). Epub 2023 Mar 6. PMID: 36986338 Abstract Title:  Preventing Persistence of HPV Infection with Natural Molecules. Abstract:  Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence.

read more

PMID:  Eur Rev Med Pharmacol Sci. 2023 Apr ;27(3 Suppl):37-45. PMID: 37129334 Abstract Title:  Hyaluronic acid accelerates re-epithelialization and healing of acute cutaneous wounds. Abstract:  OBJECTIVE: Hyaluronic acid has been efficient in ameliorating and supporting recovery in both chronic and acute lesions. The aim of this study was to assess the effectiveness of hyaluronic acid-based cream and gauze pads in cutaneous wounds.PATIENTS AND METHODS: This retrospective and prospective study examines the use of a 0.2% hyaluronic acid cream or gauze-pads application (Connettivina Bio). 85 patients participated in the study and were affected by wounds of different etiologies, comprising superficial trauma wounds (20), surgical sutures (15), first- and second-degree burns (15), dermabrasions (30) and ulcers of different etiologies (5). We analyzed the healing process in terms of progression and wound quality. Moreover, we performed biopsies (not on all patients) to evaluate the grade of re-epithelialization.RESULTS: We observed a reduction in the mean surface area of the wounds, precisely 456 mm2 at baseline to 147 mm2 after six weeks with an average 80% decrease in the wound surface area. No fibrin tissue was observed, and a small amount of exudate was noted in 91% of wounds. Hyaluronic acid cream and gauze-pads-based treatments were well tolerated by patients. All groups showed a decrease of inflammation with a progressive increase of collagen fibers and granulation tissue.CONCLUSIONS: The treatment with hyaluronic acid 0.2% yielded remarkable outcomes in the re-epithelialization of superficial wounds and provided favorable recovery and tolerance for patients.

read more

PMID:  Int J Mol Sci. 2023 Apr 14 ;24(8). Epub 2023 Apr 14. PMID: 37108462 Abstract Title:  Hyaluronic Acid-Based Nanosystems for CD44 Mediated Anti-Inflammatory and Antinociceptive Activity. Abstract:  The nervous and immune systems go hand in hand in causing inflammation and pain. However, the two are not mutually exclusive. While some diseases cause inflammation, others are caused by it. Macrophages play an important role in modulating inflammation to trigger neuropathic pain. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has a well-known ability to bind with the cluster of differentiation 44 (CD44) receptor on classically activated M1 macrophages. Resolving inflammation by varying the molecular weight of HA is a debated concept. HA-based drug delivery nanosystems such as nanohydrogels and nanoemulsions, targeting macrophages can be used to relieve pain and inflammation by loading antinociceptive drugs and enhancing the effect of anti-inflammatory drugs. This review will discuss the ongoing research on HA-based drug delivery nanosystems regarding their antinociceptive and anti-inflammatory effects.

read more

PMID:  Biomed Pharmacother. 2023 Jul ;163:114761. Epub 2023 Apr 29. PMID: 37126929 Abstract Title:  Vitamin B12 alleviates myocardial ischemia/reperfusion injury via the SIRT3/AMPK signaling pathway. Abstract:  AIM: To examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action.METHODS: Mice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) occlusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring lactate dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury.RESULTS: We found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indicated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury.CONCLUSION: High doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accumulation of reactive oxygen species and apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage.

read more

PMID:  Cureus. 2023 Mar ;15(3):e35929. Epub 2023 Mar 9. PMID: 37050999 Abstract Title:  The Effect of High-Dose Methyl Vitamin B12 Therapy on Epileptogenesis in Rats: An In Vivo Study. Abstract:  Introduction Epileptogenesis has been considered one of the most prevalent diseases affecting significant numbers of individuals worldwide. Since vitamin B12 has been reported to possess antiepileptic effects, this supports that vitamin B12 deficiency is correlated to seizure occurrence. Hence, this study aimed to evaluate the neuroprotective effects of vitamin B12 injection on pentylenetetrazole (PTZ)-induced rats. Methods The study was performed using 40 adult female Sprague-Dawley rats (~250 g). A 45 mg/kg PTZ was intraperitoneally injected into rat models to induce seizure effects. Different groups of rat models received methyl vitamin B12 therapy at different dosages, a low dosage of 45g/kg and a high dosage of 85g/kg, at different pre-treatment periods, one day and two weeks prior to PTZ injection. A control group, which received only PTZ injection, served as a reference. The seizure latency, seizure intensity, and differences in the quality of seizures and their characteristics, from simple twitches to complete seizures, were observed after 30 minutes of PTZ injection. Results In general, the latency to convulsion significantly increased when vitamin B12 pre-treatment was employed. The longest latency time (LT) of 520.6373.83 seconds was observed when a high dosage of vitamin B12 at 85g/kg was injected one day prior to PTZ inoculation, which was significantly higher than that of the control group at 176.8862.67 seconds (P

read more

PMID:  Front Immunol. 2023 ;14:1048790. Epub 2023 Mar 13. PMID: 36993968 Abstract Title:  Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19methyl-dependent changes in epigenetic markings. Abstract:  COVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genesmethyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, that regulates the bioavailability of methyl. Accordingly, B12-induced downregulation ofstrongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic markings in leukocytes favorably regulates central components of COVID-19 physiopathology.

read more

PMID:  J Nepal Health Res Counc. 2023 Mar 10 ;20(3):702-707. Epub 2023 Mar 10. PMID: 36974860 Abstract Title:  High Burden of Vitamin B12 Deficiency among Adults and Elderly. Abstract:  BACKGROUND: Deficiency of vitamin-B12 is widespread. Adults and the elderly are particularly susceptible to vitamin-B12 deficiency. This study investigated the burden of vitamin-B12 deficiency and insufficiency among adults and the elderly attending a tertiary care hospital in Nepal.METHODS: This is a retrospective chart review conducted at Dhulikhel hospital. We reviewed records of 1615 patients investigating Vitamin-B12 level (pmol/L) at the clinical biochemistry laboratory from laboratory management database MIDAS between June 2020 and December 2021. Vitamin-B12 level was measured using enzyme immunoassay in Abbott Architect i1000SR analyzer. The categorical variables are presented as frequency and percentage; and numerical variables as means and standard deviations, or median and Interquartile range. Pearson Chi-square test was used to determine association between categorical variables. Mann Whitney test and Kruskal Wallis H test were used to compare Vitamin-B12 level by categories.RESULTS: There were 1454 participants of which 33.5% of the patients were deficient, 27.9% were borderline deficient, while 38.7% had adequate vitamin B12 levels. Young adults(170.4 pmol/L) had a lower median vitamin B12 level than middle-aged adults (183.7pmol/L) and the elderly population (247.9pmol/L) (P

read more