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We all want to live a long life, but did you know eating these simple foods has been proven scientifically to prevent and in some cases reverse the #1 cause of death in the modern world?

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PMID:  Heliyon. 2022 Dec ;8(12):e11943. Epub 2022 Dec 13. PMID: 36590574 Abstract Title:  Mangosteen vinegar from Garcinia mangostana: quality improvement and antioxidant properties. Abstract:  Mangosteen (Linn.) fruit is rich in phenolic compounds which function as antioxidants and play a role in anti-inflammation, anti-hyperlipidemia, and anti-diabetic nephropathy. To investigate mangosteen vinegar (MV) by steaming under high pressure, explore the effects of fermentation, antioxidant activity, and sensory evaluation acceptable using the 9 -point Hedonic scale. Steamed mangosteen was processed to produce 3 types of mangosteen vinegar: mangosteen rind vinegar (MRV), mangosteen flesh vinegar (MFV), and mangosteen rind plus flesh vinegar (MRFV). All 3 kinds of mangosteen vinegar were obtaining>4% acetic acid and significantly higher total phenolic content (TPC), total flavonoid content (TFC), and free radical scavenging ABTS+ and DPPH- antioxidant activity than apple cider vinegar (ACV) (

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PMID:  BMC Med. 2023 May 5 ;21(1):174. Epub 2023 May 5. PMID: 37147641 Abstract Title:  Vitamin K2 supplementation improves impaired glycemic homeostasis and insulin sensitivity for type 2 diabetes through gut microbiome and fecal metabolites. Abstract:  BACKGROUND: There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention.METHODS: We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism.RESULTS: After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P=0.048), insulin (P=0.005), and HbA1c levels (P=0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P=0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations.CONCLUSIONS: Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management.TRIAL REGISTRATION: The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).

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PMID:  Arq Gastroenterol. 2023 ;60(1):144-154. PMID: 37194773 Abstract Title:  ALZHEIMER'S DISEASE AND ITS RELATIONSHIP WITH THE MICROBIOTA-GUT-BRAIN AXIS. Abstract:  BACKGROUND: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. Several pathways enable bidirectional communication between the central nervous system (CNS), the intestine and its microbiota, constituting the microbiota-gut-brain axis.OBJECTIVE: Review the pathophysiology of AD, relate it to the microbiota-gut-brain axis and discuss the possibility of using probiotics in the treatment and/or prevention of this disease.METHODS: Search of articles from the PubMed database published in the last 5 years (2017 to 2022) structure the narrative review.RESULTS: The composition of the gut microbiota influences the CNS, resulting in changes in host behavior and may be related to the development of neurodegenerative diseases. Some metabolites produced by the intestinal microbiota, such as trimethylamine N-oxide (TMAO), may be involved in the pathogenesis of AD, while other compounds produced by the microbiota during the fermentation of food in the intestine, such as D-glutamate and fatty acids short chain, are beneficial in cognitive function. The consumption of live microorganisms beneficial to health, known as probiotics, has been tested in laboratory animals and humans to evaluate the effect on AD.CONCLUSION: Although there are few clinical trials evaluating the effect of probiotic consumption in humans with AD, the results to date indicate a beneficial contribution of the use of probiotics in this disease.

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PMID:  Sports Med Open. 2023 May 16 ;9(1):31. Epub 2023 May 16. PMID: 37193828 Abstract Title:  Effects of Probiotics and Vitamin DSupplementation on Sports Performance Markers in Male Mixed Martial Arts Athletes: A Randomized Trial. Abstract:  BACKGROUND: Strategies targeted at the intestine microbiome seem to be beneficial for professional athletes. The gut-muscle axis is associated with the inflammatory state, glucose metabolism, mitochondrial function, and central nervous system health. All these mechanisms may affect maximal oxygen uptake, muscle strength, and training adaptation. Moreover, the positive effect of certain bacterial strains may be enhanced by vitamin D. Thus, this study aimed to assess and compare the level of selected markers of sports performance of mixed martial arts (MMA) athletes supplemented with vitamin Dor probiotics combined with vitamin D.METHODS: A 4-week randomized double-blind placebo-controlled clinical trial was conducted with 23 MMA male athletes assigned to the vitamin Dgroup (Vit D; n=12) or probiotics+vitamin Dgroup (PRO+VitD; n=11). Repeated measures of the creatine kinase level, lactate utilization ratio, and anaerobic performance were conducted.RESULTS: After 4 weeks of supplementation, we found lower lactate concentrations 60 min after the acute sprint interval in the PRO+VitD group when compared to the Vit D group (4.731.62 and 5.881.55 mmol/L; p

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PMID:  Probiotics Antimicrob Proteins. 2023 May 16. Epub 2023 May 16. PMID: 37191780 Abstract Title:  Immunomodulatory Activity of Probiotics in Models of Bacterial Infections. Abstract:  As resistance to conventional antibiotics among bacteria continues to increase, researchers are increasingly focusing on alternative strategies for preventing and treating bacterial infections, one of which is microbiota modulation. The objective of this review is to analyze the scientific literature on the immunomodulatory effects of probiotics in bacterial infections. This is an integrative review of the literature based on systematic steps, with searches performed in the databases Medline, PubMed, Scopus, Embase, and ScienceDirect. The most prevalent bacterial genera used to evaluate infectious processes were Salmonella, Escherichia, Klebsiella, and Streptococcus. Lactobacillus was the most commonly used probiotic genus, with Lactobacillus delbrueckii subsp. bulgaricus is the most frequently used species. In most studies, prophylactic treatment with concentrations of probiotics equal to or greater than 8 log CFU/mL was chosen. However, there was considerable heterogeneity in terms of effective treatment duration, indicating that the results cannot be generalized across all studies. This review found that probiotics interact with the immune system through different mechanisms and have a positive effect on preventing different types of bacterial infections.

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PMID:  Cancers (Basel). 2023 Apr 21 ;15(8). Epub 2023 Apr 21. PMID: 37190329 Abstract Title:  Pterostilbene and Probiotic Complex in Chemoprevention of Putative Precursor Lesions for Colorectal Cancer in an Experimental Model of Intestinal Carcinogenesis with 1,2-Dimethylhydrazine. Abstract:  Dietary supplementation with pterostilbene (PS) and/or a probiotic (PRO) may ameliorate the intestinal microbiota in disease conditions. This study aims to evaluate PS and PRO for the chemoprevention of putative precursor lesions for colorectal cancer (CRC) in an experimental model of intestinal carcinogenesis with 1,2-dimethylhydrazine (1,2-DMH). Sixty male Wistar rats were equally divided into five groups: Sham, 1,2-DMH, 1,2-DMH + PS, 1,2-DMH + PRO, and 1,2-DMH + PS + PRO. PRO (510/mL) was offered in water, and PS (300 ppm) was provided in the diet ad libitum. 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. PRO alone and PRO combined with PS were the best intervention strategies to improve experimental 1,2-DMH-induced CRC regarding several parameters of carcinogenesis. Our findings may contribute to the development of novel preventive strategies for CRC and may help to identify novel modulators of colon carcinogenesis.

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PMID:  Diabetes Metab Res Rev. 2023 May 14:e3655. Epub 2023 May 14. PMID: 37183580 Abstract Title:  Probiotics, prebiotics, and synbiotics in type 1 diabetes mellitus: A systematic review and meta-analysis of clinical trials. Abstract:  Dysbiosis or imbalance of microbes in the gut has been associated with susceptibility and progression of type 1 diabetes mellitus (T1DM). The present systematic review and meta-analysis examined the effects of probiotics, prebiotics, and synbiotics on fasting blood glucose (FBG), haemoglobin A1c (HbA1c), C-peptide, and insulin requirements in T1DM patients. A systematic search for trials published up to October 2022 was conducted in PubMed, EMBASE, Scopus, Google Scholar, ScienceDirect, Web of Science, and the Central Cochrane Library. Random effect models were used to synthesise quantitative data by STATA. After the evaluation of 258 identified entries, five randomised controlled trials (n = 356; mean age = 11.7 years old) were included. The pooled effect size showed that FBG decreased following probiotic supplementation (weighted mean difference = -31.24 mg/dL; 95% confidence interval = -45.65, -16.83; p 

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PMID:  Curr Dev Nutr. 2023 Mar ;7(3):100039. Epub 2023 Feb 18. PMID: 37181929 Abstract Title:  Fermented Vegetables as a Potential Treatment for Irritable Bowel Syndrome. Abstract:  Foods and supplements containing microorganisms with expected beneficial effects are increasingly investigated and utilized in the treatment of human illness, including irritable bowel syndrome (IBS). Research points to a prominent role of gut dysbiosis in the multiple aberrations in gastrointestinal function, immune balance, and mental health seen in IBS. The proposition of the current Perspective is that fermented vegetable foods, in combination with a healthy and stable diet, may be particularly useful for addressing these disturbances. This is based on the recognition that plants and their associated microorganisms have contributed to shaping human microbiota and adaptation over evolutionary time. In particular, lactic acid bacteria with immunomodulatory, antipathogenic, and digestive properties are prevalent in products such as sauerkraut and kimchi. Additionally, by adjusting the salt content and fermentation time, products with a microbial and therapeutic potential beyond that of regular ferments could potentially be produced. Although more clinical data are required to make firm assertions, the low-risk profile, combined with biological considerations and reasoning and considerable circumstantial and anecdotal evidence, indicate that fermented vegetables are worthy of consideration by health professionals and patients dealing with IBS-related issues. To maximize microbial diversity and limit the risk of adverse effects, small doses of multiple products, containing different combinations of traditionally fermented vegetables and/or fruits, is suggested for experimental research and care.

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PMID:  Front Public Health. 2023 ;11:1155989. Epub 2023 Apr 27. PMID: 37181698 Abstract Title:  Regular consumption of pickled vegetables and fermented bean curd reduces the risk of diabetes: a prospective cohort study. Abstract:  OBJECTIVE: The global incidence of diabetes is rising, in part due to the widespread adoption of poor dietary habits. Fermented vegetables have numerous health benefits and are generally affordable. Here, we examined whether regular consumption of pickled vegetables or fermented bean curd reduces the risk of diabetes.METHODS: A total of 9,280 adults (18 years of age) were recruited via multi-stage sampling from 48 townships in China between 2010 and 2012 for this 10-year prospective study. In addition to demographic information, monthly consumption levels of pickled vegetables and fermented bean curd were recorded. Participants were then monitored for diabetes onset. After the final follow-up, logistic regression analyses with multiple covariant corrections were conducted to estimate the changes in diabetes risk associated with consumption of pickled vegetables and fermented bean curd compared to non-consumption.RESULTS: A total of 6,640 subjects without diabetes at the start of the study were followed up for a median period of 6.49 years, among whom 714 were diagnosed with diabetes during the study. According to a regression model with multivariable adjustment, diabetes risk was significantly reduced by consumption of 0-0.5 kg/month of pickled vegetables (OR = 0.77, 95% CI: 0.63, 0.94) and further reduced by consumption of>0.5 kg/month of pickled vegetables (OR = 0.37, 95% CI: 0.23, 0.60) compared to no consumption (both-trend

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PMID:  Saudi Pharm J. 2023 May ;31(5):639-654. Epub 2023 Mar 10. PMID: 37181140 Abstract Title:  Metabolite profiling, hypolipidemic, and anti-atherosclerosis activity of mixed vegetable fermentation extract. Abstract:  Although positive association between fermented vegetables intake with the risk of coronary heart disease (CHD) has increased attention nowadays, the metabolite profiling and the mechanism of action are still elusive. This study designed to investigate the secondary metabolites, hypolipidemic, and anti-atherogenic effect of mixed vegetable fermentation extract (MVFE). The metabolite screening of the MVFE was assessed using the Liquid Chromatography Tandem Mass Spectrophotometer (LC-MS/MS) method. The result of LC-MS/MS was used as ligands to inhibit the binding of oxidized LDL (oxLDL) and Cluster Differentiation 36 (CD36), Scavenger Receptor A1 (SRA1), Lectin-type oxidized LDL receptor 1 (LOX1). This work was performed with molecular docking using Discovery Studio 2021, PyRx 0.9, and Autodock Vina 4.2 followed by analyzing Network Pharmacology, Protein Protein Interaction (PPI) using Cytoscape 3.9.1 and String 2.0.0. Finally, the clinical effect of MVFE was evaluated usingstudy. Twenty rabbits were assigned to normal, negative control, and MVFE group that were fed with standard diet, high fat diet (HFD), HFD supplemented with MVFE 100, 200 mg/kg BW, respectively. The serum level of Total Cholesterol (TC) and Low-Density Lipoprotein (LDL-c) were detected at the end of week 4. The LC-MS/MS analysis identified 17 compounds categorized as peptides, fatty acids, polysaccharides, nucleoside, flavonoids, flavanols, and phenolic compounds. Based on the docking study, more negative binding affinity was observed in the interaction between metabolites with the scavenger receptors (SR) than simvastatin. The number of nodes and edges based on Network Pharmacology analysis were 268 and 482, respectively. The PPI network showed that MVFE metabolites exerts its athero-protective effect by modulating various cellular processes including inflammation, improvement of endothelial function, and modulation of lipid metabolism. Blood TC and LDL-c concentrations in the negative control (458.82  82.03; 191.87  92.16 mg/dL) were higher significantly compared to the normal group (87.03  29.27; 43.33  5.75 mg/dL). The MVFE administration decreased the TC (100, 200 mg/kg BW MVFE: 269.96  85.34; 130.17  45.02 mg/dL) and LDL-c level (100, 200 mg/kg BW MVFE = 87.24  22.85; 41.82  11.08 mg/dL) dose-dependently (p 

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PMID:  BMC Res Notes. 2023 May 18 ;16(1):82. Epub 2023 May 18. PMID: 37202827 Abstract Title:  In vitro anti-Toxoplasma gondii activity of Ganoderma lucidum extracts. Abstract:  OBJECTIVE: Ganoderma extracts have the potential to be used as anti-cancer, anti-inflammatory, immunomodulator, and antimicrobial agents, as evaluated in numerous studies. This study was aimed to determine the lethal and inhibitory effects of aqueous, hydroalcoholic, and alcoholic extracts of Ganoderma lucidum on Toxoplasma gondii RH strain tachyzoites, in vitro.RESULTS: All three types of extracts showed toxoplasmacidal effects. The highest percentage of mortality was related to hydroalcoholic extract. The EC50 of Ganoderma extracts for tachyzoites were 76.32, 3.274, and 40.18 for aqueous, hydroalcoholic and alcoholic extracts, respectively. The selectivity index obtained for hydroalcoholic extract was 71.22, showing the highest activity compared to other extracts. According to our findings, the hydroalcoholic part was the most effective substance among the extracts. This basic study showed obvious anti-toxoplasma effect of Ganoderma lucidum extracts. These extracts can be used as candidates for further in-depth and comprehensive studies especially In vivo experiments to prevent toxoplasmosis.

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PMID:  Int J Med Mushrooms. 2023 ;25(5):1-15. PMID: 37183915 Abstract Title:  The Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Can Combat Cytokine Storm and Other COVID-19 Related Pathologies: A Review. Abstract:  Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is characterized by acute respiratory distress syndrome (ARDS) facilitated by cytokine storm and other risk factors that increase susceptibility and complications leading to death. Emerging as a major global public health challenge, the disease has claimed more than 6 million lives and caused catastrophic global economic disruptions. However, there are concerns about the safety as well as the efficacy of drugs and vaccines presently used to control the pandemic, therefore necessitating intense global search for safe natural products that can effectively and safely combat it. This work reviews studies on lingzhi or reishi medicinal mushroom, Ganoderma lucidum and its properties that may potentially combat SARS-CoV-2 infection and the co-morbidities. Available evidence suggests that medicinal properties of the Ganoderma mushroom can combat the complications of SARS-CoV-2 infection and the co-morbidities that can aggravate the severity of the disease. Preclinical and clinical evaluation to establish dose, efficacy, and potential toxicity and possible use in the management of COVID-19 is recommended.

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PMID:  Food Chem X. 2023 Jun 30 ;18:100682. Epub 2023 Apr 23. PMID: 37168720 Abstract Title:  Structural characterization of polysaccharides after fermentation fromand its antioxidant activity in HepG2 cells induced by HO. Abstract:  In this study,ATCC14917 was used to fermentspore powder. Two polysaccharides were purified from unfermented (GLP) and fermented (FGLP)spore powder. The chemical structure and antioxidant activity of the polysaccharides were studied. Finally, the effect of GLP and FGLP on the oxidative stress regulation pathway in HepG2 cells was explored. The results showed that the main structural characteristics ofpolysaccharides remained unchanged during the fermentation. However, the average molecular weight () ofpolysaccharides decreased from 1.12  10 Da to 0.89  10 Da. Besides this, the contents of mannose, galactose, and glucuronic acid increased, while the contents of xylose and glucose were decreased. In addition, the content of uronic acid was raised, and the apparent structure was changed from smooth and hard to porous and loose. In antioxidant studies, intracellular ROS and MDA contents in the oxidative stress model were decreased, and-AOC content was increased under GLP and FGLP intervention. In the investigation of the regulation pathway, Nrf-1 gene expression was up-regulated, and Keap1 gene expression was down-regulated under GLP and FGLP intervention. The antioxidant genes NQO1 and NO-1 expressions were increased to activate the activities of antioxidant enzymes CAT, SOD and GSH-PA to resist oxidative stress. Compared with GLP, FGLP has a stronger regulatory role in this pathway, thus showing more potent antioxidant activity. This experiment is beneficial to the further utilization ofspore powder.

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PMID:  Chin J Cancer Res. 2023 Apr 30 ;35(2):176-190. PMID: 37180834 Abstract Title:  Aqueous-soluble components of sporoderm-removedspore powder promote ferroptosis in oral squamous cell carcinoma. Abstract:  OBJECTIVE: Ferroptosis is a novel cell death process which displays a promising role in cancer treatment. However, clinically available drugs targeting ferroptosis are rarely used, and yet there are no studies reporting on inducing ferroptosis via Chinese herbal extracts. Here we explored the tumor inhibition effects of() on oral squamous cell carcinoma (OSCC). Specifically, we aimed to clarify the biological mechanism of components in the dietary, aqueous-soluble sporoderm-removedspore powder (A-GSP).METHODS: Preliminary transcriptome analysis revealed the significant enrichment of the ferroptosis pathway. Cellular Fe, glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxide levels were measured to identify ferroptosis occurrence. Western blotting was used to measure ferroptosis-related proteins. Changes in mitochondria morphology and function were observed with transmission electron microscopy (TEM) and ATP detection assays. Ferroptosis inhibitor ferrostatin-1 was then used to verify the anti-tumor effects of A-GSP. Finally, nude mice xenograft models of oral cancer confirmed that A-GSP inhibited tumor growth.RESULTS: A-GSP promoted ferroptosis in oral cancer cells by inducing Feinflux, GSH depletion, as well as lipid peroxide and ROS accumulation. Ferroptosis-related proteins exhibited corresponding changes, particularly Acyl-coA synthetase long chain family member 4 (ACSL4) increase and glutathione peroxidase 4 (GPX4) decrease. A-GSP considerably lowered mitochondrial volume and ridge number, while significantly decreasing ATP production. Ferrostatin-1 reversed all of these A-GSP-induced changes., A-GSP exerted a ferroptosis-mediated tumor-suppressing effect without observable adverse reactions.CONCLUSIONS: Our findings demonstrate the therapeutic potential of A-GSP for treating patients with OSCC by targeting ferroptosis.

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PMID:  Dis Markers. 2023 ;2023:1520132. Epub 2023 Apr 14. PMID: 37091893 Abstract Title:  Evaluation ofMushroom Effects on Histopathological Changes in Organs of Diabetic Rats. Abstract:  Diabetes mellitus (DM) is a metabolic disorder that can be categorized mainly into type 1 and type 2. Diabetes type 1 is caused due to-cell destruction, whereas type 2 is caused by the resistance of cell receptors. Many therapies are available for the management of diabetes, but they have some side effects, and as a result of this, people are attracted to natural treatments.mushrooms are well documented for their medicinal attributes and their role in the treatment of diseases like cancer, infectious disease, neurodiseases, and inflammatory disease. The protective mechanism of the() mushroom and its detailed histological study on kidneys and the liver in diabetic conditions were unexplored. The present study evaluated the effects ofaqueous extract on histological changes in the diabetic rat model. Male Wistar albino rats were used to create the diabetic model by using streptozotocin (STZ) intraperitoneal (IP) injection. The animals were separated into five different groups, with six animals in each. Only group I, animals that did not receive STZ, was considered a normal control. Group II was a diabetic control and received normal saline, and group III was a drug control and received metformin as a standard drug. Groups IV and V were dosing groups, which received the aqueous extract ofin 250mg/kg and 500mg/kg of body weight concentrations, labeled as T1 and T2 groups, respectively. The T1 and T2 groups clearly showed their potential to reverse the histopathological changes in the kidney and liver. However, the T2 group was more effective than the T1 group, as results indicate that functions of the glomerulus and its structural deformity were restored to their near-natural form in the T2 group. In the case of the liver, the histological changes like the dilatation of sinusoids, more numbers of the Kupffer cell formation, and necrosis were restored in the T2 group. All these results proved the potential ofagainst the side effects of diabetes. It could protect the organs from developing diabetic nephropathy (DN) and liver-related diseases like cirrhosis and nonalcoholic fatty liver disease (NAFLD).

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PMID:  Food Funct. 2023 Jun 6 ;14(11):5326-5341. Epub 2023 Jun 6. PMID: 37204244 Abstract Title:  Maternal supplementation with human milk-derivedWLPL04 affects the immunity and gut microbiota of offspring rats. Abstract:  Pregnancy and lactation are a window period during which interventions on mothers bring beneficial effects to newborns. This study aims to investigate the effects of maternal supplementation with human-milk-derivedWLPL04-36e during pregnancy and lactation on the physiology, immunity and gut microbiota of dams and their offspring. We found that after maternal supplementation,WLPL04-36e could be detected in the intestines and extraintestinal tissues (liver, spleen, kidneys, mammary gland, MLN and brain) of dams, as well as in the intestines of their offspring. Maternal supplementation withWLPL04-36e could significantly increase the body weights of dams and their offspring during the middle to late lactation period, elevate the serum levels of IL-4, IL-6, and IL-10 of dams and IL-6 level of offspring, and increase the proportion of spleen CD4+ T lymphocytes of the offspring. Moreover,WLPL04-36e supplementation could increase the alpha diversity of milk microbiota during early and middle lactation periods, and elevated the abundance ofin the intestines of offspring at week 2 and week 3 after birth. These results suggest that maternal supplementation with human-milk-derivedcan regulate the immunity and intestinal microbiota composition of offspring and play positive roles in the growth of offspring.

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PMID:  Food Funct. 2023 Jun 6 ;14(11):5167-5181. Epub 2023 Jun 6. PMID: 37184519 Abstract Title:  Gastroprotective effects of ginsenoside Rh4 against ethanol-induced gastric mucosal injury by inhibiting the MAPK/NF-B signaling pathway. Abstract:  Ginsenoside Rh4, a bioactive component extracted from, exhibits various pharmacological activities, such as anti-inflammatory, anti-oxidation, anti-diabetes, anti-obesity, antitumor and immunity enhancement. However, the gastroprotective effect of ginsenoside Rh4 remains unknown. The present study evaluated the gastroprotective effect and potential mechanism of ginsenoside Rh4 in an ethanol-induced gastric ulcer model. Ginsenoside Rh4 (15, 30, and 60 mg kg) and omeprazole (30 mg kg) were administered orally for 7 days. The results showed that pretreatment with ginsenoside Rh4 reduced the gastric injury area and percentage of mucosal lesions in gastric tissue. Besides, treatment with ginsenoside Rh4 increased superoxide dismutase (SOD) activity, glutathione (GSH) and nitric oxide (NO) levels, reduced the content of malonaldehyde (MDA), tumor necrosis factor-(TNF-), interleukin-6 (IL-6), and interleukin-1(IL-1), mediated the prostaglandin E-2-cyclooxygenase-2 (PGE2-Cox-2) pathway, and mitigated inflammation and oxidative stressblockade of proinflammatory mitogen-activated protein kinase-nuclear factorB (MAPK/NF-B) signaling pathways. Furthermore, ginsenoside Rh4 significantly enhanced the protein expression of B-cell lymphoma gene 2 (Bcl-2), decreased the protein expression of Bcl-2-associated X protein (Bax) and tumor necrosis factor receptor superfamily member 6 (Fas), and inhibited the number of apoptotic cells in gastric tissues. The present work demonstrated that ginsenoside Rh4 exerted a considerable gastroprotective effect against ethanol-induced gastric ulcers in rats.

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PMID:  Front Pharmacol. 2023 ;14:1166898. Epub 2023 Apr 28. PMID: 37188264 Abstract Title:  Hypolipidemic effect and molecular mechanism of ginsenosides: a review based on oxidative stress. Abstract:  Hyperlipidemia is considered a risk factor for cardiovascular and endocrine diseases. However, effective approaches for treating this common metabolic disorder remain limited. Ginseng has traditionally been used as a natural medicine for invigorating energy or "Qi" and has been demonstrated to possess antioxidative, anti-apoptotic, and anti-inflammatory properties. A large number of studies have shown that ginsenosides, the main active ingredient of ginseng, have lipid-lowering effects. However, there remains a lack of systematic reviews detailing the molecular mechanisms by which ginsenosides reduce blood lipid levels, especially in relation to oxidative stress. For this article, research studies detailing the molecular mechanisms through which ginsenosides regulate oxidative stress and lower blood lipids in the treatment of hyperlipidemia and its related diseases (diabetes, nonalcoholic fatty liver disease, and atherosclerosis) were comprehensively reviewed. The relevant papers were search on seven literature databases. According to the studies reviewed, ginsenosides Rb1, Rb2, Rb3, Re, Rg1, Rg3, Rh2, Rh4, and F2 inhibit oxidative stress by increasing the activity of antioxidant enzymes, promoting fatty acid-oxidation and autophagy, and regulating the intestinal flora to alleviate high blood pressure and improve the body's lipid status. These effects are related to the regulation of various signaling pathways, such as those of PPAR, Nrf2, mitogen-activated protein kinases, SIRT3/FOXO3/SOD, and AMPK/SIRT1. These findings suggest that ginseng is a natural medicine with lipid-lowering effects.

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n/a PMID:  Biomed Pharmacother. 2023 Jul ;163:114870. Epub 2023 May 13. PMID: 37187019 Abstract Title:  Ginsenoside Rb1 stabilized and paclitaxel / protopanaxadiol co-loaded nanoparticles for synergistic treatment of breast tumor. Abstract:  Ginsenosides are the major and key components for ginseng to exert its wide and beneficial therapeutic efficacy in clinic. Meanwhile, many ginsenosides and their metabolites showed in vitro an in vivo anti-tumor activity, among which ginsenoside Rb1 has attracted much attention due to its good solubility and amphipathy. In this study, the self-assembly behavior of Rb1 was investigated and the Rb1 nano-assembly could further stabilize or encapsulated hydrophobic drugs such as protopanaxadiol (PPD) and paclitaxel (PTX) to form nanoparticles, based on which, a natural nanoscale drug delivery system, ginsenoside Rb1 stabilized and PTX/PPD co-loaded nanoparticles (GPP NPs) were prepared. The resultant GPP NPs exhibited a small particle size of 126.2 nm, a narrow size distribution (PDI=0.145), and a zeta potential of -27.3 mV. PTX loading content was 11.06% with an encapsulation efficiency of 93.86%. GPP NPs were spherical and stable in normal saline, 5% glucose, PBS, plasma, or on-shelf storage for 7 days. Both PTX and PPD existed in an amorphous state in GPP NPs and were released in a sustained pattern. GPP NPs showed 10-fold higher in vitro anti-tumor activity of than PTX injections. In the in vivo experiment, GPP NPs achieved a much higher tumor inhibition rate than PTX injections (64.95% vs 43.17%, P < 0.01) and certain tumor target ability. In conclusion, GPP NPs had significantly enhanced anti-tumor efficacy and improved tumor microenvironment, thus were promising to be developed into a novel anti-tumor agent for the treatment of breast tumor.

PMID:  Food Funct. 2023 May 22 ;14(10):4696-4705. Epub 2023 May 22. PMID: 37186251 Abstract Title:  Ginsenoside Rg1 activates brown adipose tissue to counteract obesity in high-fat diet-fed mice by regulating gut microbes and bile acid composition. Abstract:  Obesity is a global health problem strongly linked to gut microbes and their metabolites. In this study, ginsenoside Rg1 (Rg1) reduced lipid droplet size and hepatic lipid accumulation by activating uncoupling protein 1 expression in brown adipose tissue (BAT), which in turn inhibited high-fat diet (HFD)-induced weight gain in mice. Furthermore, the intestinal flora of mice was altered, the abundance of,,,andwas upregulated, and the concentrations of fecal bile acids were altered, with cholic acid and taurocholic acid concentrations being significantly increased. In addition, the beneficial effects of Rg1 were eliminated in mice treated with a combination of antibiotics. In conclusion, these results suggest that Rg1 activates BAT to counteract obesity by regulating gut microbes and bile acid composition in HFD-fed mice.

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PMID:  Molecules. 2023 May 3 ;28(9). Epub 2023 May 3. PMID: 37175273 Abstract Title:  Immunomodulatory, Anti-Inflammatory, and Anti-Cancer Properties of Ginseng: A Pharmacological Update. Abstract:  Ginseng, a medicinal plant of the genus, boasts a rich historical record of usage that dates back to the Paleolithic period. This botanical is extensively acknowledged and consumed in Eastern countries for its therapeutic properties, and, in Western countries, it is becoming increasingly popular as a remedy for fatigue and asthenia. This review provides an update on current research pertaining to ginseng and its isolated compounds, namely, ginsenosides and polysaccharides. The primary focus is on three crucial pharmacological activities, namely, immunomodulation, anti-inflammatory, and anti-cancer effects. The review encompasses studies on both isolated compounds and various ginseng extracts obtained from the root, leaves, and berries.

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PMID:  Int J Med Mushrooms. 2023 ;25(5):17-30. PMID: 37183916 Abstract Title:  Effect of the Lingzi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) on Hyperglycemia and Dyslipidemia with Experimental Metabolic Syndrome. Abstract:  The effect of Ganoderma lucidum hot water extract of submerged cultivated mycelium suspensia on carbohydrate metabolism and lipid profile during fructose-induced metabolic syndrome in rats was studied. The outbred white male Wistar rats, in which metabolic syndrome was induced by consuming a 10% fructose solution instead of drinking water for 42 days, were used. After the induction of metabolic syndrome, the mycelium of G. lucidum in the form of water suspension (a dose of 1 g/kg of the animal's body weight) was administered to animals per os for 7 and 14 days. Glucose concentration was determined using the glucose oxidase method. The content of glycosylated hemoglobin in erythrocytes was determined by the colorimetric method. The concentration of triglycerides, cholesterol, high-density lipoproteins, and low-density lipoproteins in blood plasma was determined by enzymatic methods. A significant decrease in the content of glycosylated hemoglobin was established in animals with metabolic syndrome against the background of administration of the studied suspension. Under the conditions of experimental metabolic syndrome, the administration of mycelium for 7 and 14 days led to a decrease in the concentration of triglycerides by 17.8 and 44.8%, cholesterol by 10.7 and 21.3%, low-density lipoproteins by 14.8 and 28.4%, and to an increase in high-density lipoproteins concentration by 11.9 and 21.5%, compared with metabolic syndrome. The obtained results demonstrate the corrective effect of the suspension of the G. lucidum powdered mycelium on carbohydrate and lipid metabolism, which was directly proportional to the duration of administration.

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PMID:  Food Funct. 2023 May 22 ;14(10):4607-4620. Epub 2023 May 22. PMID: 37158366 Abstract Title:  leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration. Abstract:  Tumor-associated macrophages (TAMs) participate in tumorigenesis, growth, invasion as well as metastasis by facilitating an immunosuppressive tumor microenvironment. Reversing the pro-tumoral M2 phenotype of TAMs has become a hot spot in advancing cancer immunotherapy. In the current study, the content ofleaf polysaccharides (MOLP) was determined and characterized, along with the anti-cancer mechanism of MOLP studied in a Lewis lung cancer (LLC) tumor-bearing mouse model and bone marrow-derived macrophages. The monosaccharide composition and gel permeation chromatography analyses show that MOLP are mainly composed of galactose, glucose, and arabinose, with approximately 17.35 kDa average molecular weight ().studies demonstrate that MOLP convert TAMs from the immunosuppressive M2 phenotype to the antitumor M1 phenotype, thus inducing CXCL9 and CXCL10 expression and increasing T-cell infiltration in the tumor. Furthermore, macrophage depletion and T cell suppression demonstrated that the tumor suppressive effect of MOLP was reliant on reprogramming macrophage polarization and T cell infiltration.studies revealed that MOLP could induce the phenotypic switch from M2 macrophages to M1 by targeting TLR4. The current study highlights that MOLP are promising anticancer plant-derived polysaccharides with potential in modulating the immune microenvironment and have a bright application prospect in the immunotherapy of lung cancer.

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PMID:  Food Funct. 2023 May 22 ;14(10):4621-4631. Epub 2023 May 22. PMID: 37158592 Abstract Title:  Curcumin inhibits liquid-liquid phase separation of fused in sarcoma and attenuates the sequestration of pyruvate kinase to restore cellular metabolism. Abstract:  The abnormal accumulation of fused in sarcoma (FUS) is a pathological hallmark in a proportion of patients with frontotemporal dementia and amyotrophic lateral sclerosis. Therefore, the clearance of FUS aggregates is a possible therapeutic strategy for FUS-associated neurodegenerative diseases. This study reports that curcumin can strongly suppress FUS droplet formation and stress granule aggregation of FUS. Fluorescence spectra and isothermal titration calorimetry showed that curcumin can bind FUS through hydrophobic interactions, thereby reducing the-sheet content of FUS. Aggregated FUS sequesters pyruvate kinase, leading to reduced ATP levels. However, results from a metabolomics study revealed that curcumin changed the metabolism pattern and differentially expressed metabolites were enriched in glycolysis. Curcumin attenuated FUS aggregation-mediated sequestration of pyruvate kinase and restored cellular metabolism, consequently increasing ATP levels. These results indicate that curcumin is a potent inhibitor of FUS liquid-liquid phase separation and provide novel insights into the effect of curcumin in ameliorating abnormal metabolism.

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PMID:  Food Funct. 2023 May 22 ;14(10):4763-4776. Epub 2023 May 22. PMID: 37128768 Abstract Title:  Hyperoside inhibits pancreatic lipase activityand reduces fat accumulation. Abstract:  Hyperoside, the main component of many anti-obesity plants, might exhibit a lipase inhibition effect to reduce fat accumulation. The anti-obesity effect of hyperoside was investigated by studying its inhibitory effect and mechanism on pancreatic lipaseand evaluating its ability to reduce lipid accumulation. Hyperoside is a mixed-type inhibitor of lipase with an ICof 0.670.02 mmol L. Hyperoside changed the secondary conformation of lipase, increased the-helix content, and changed the microenvironment of lipase through static quenching. The interaction between hyperoside and lipase results from a strong binding spontaneous exothermic reaction, mainly through hydrogen bonding, van der Waals force and electrostatic force. Hyperoside protected hepatic lipid accumulation and adipose tissue hypertrophy and reduced the expression of inflammatory factors in high-fat diet-induced rats. Moreover, hyperoside had a good inhibitory effect on lipase activity in serum and increased fecal fat excretion, thereby reducing lipid absorption. This study provides theoretical support for the research and development of hyperoside in fat-reducing functional foods.

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PMID:  Food Funct. 2023 May 22 ;14(10):4792-4806. Epub 2023 May 22. PMID: 37128867 Abstract Title:  Molecular mechanism of green tea polyphenol epicatechin gallate attenuatingpathogenicity by targeting Ser/Thr phosphatase Stp1. Abstract:  In this study, through virtual screening andbioactivity assays, we discovered that (-)-epicatechin gallate (ECG), a polyphenol compound extracted from green tea, demonstrated marked anti-Ser/Thr phosphatase (Stp1) activity towards() with an ICvalue of 8.35M. By targetingStp1, ECG prevented the up-regulation of virulence gene and the formation of antibody membrane and protected the mice frominfection. Through MD simulation, the allosteric inhibitory mechanism of ECG on Stp1 was determined. The Stp1-ECG complex model underwent a significant change in conformation; its flap subdomain changed from opening to closing, whereas Stp1 activity was lost when bound to ECG. In addition, the MD simulation results of Stp1 and several tea polyphenol compounds showed that gallate groups and fewer adjacent phenolic hydroxyl groups contributed to the binding of Stp1 and inhibitors. As an inhibitor targetingStp1, ECG reduced the pathogenicity ofwithout inhibiting, which largely reduced the possibility of drug resistance. Our findings demonstrated a novel molecular mechanism of green tea as the usual drink againstinfection and elucidated the future design of allosteric inhibitors targeting Stp1.

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PMID:  Am J Reprod Immunol. 2023 Jul ;90(1):e13709. Epub 2023 May 8. PMID: 37157916 Abstract Title:  Hyperoside alleviates postmenopausal osteoporosis via regulating miR-19a-5p/IL-17A axis. Abstract:  PROBLEM: Postmenopausal osteoporosis (PMO) is a common osteoporosis. Hyperoside (Hyp), a natural flavonoid compound, has anti-osteoporotic effects, but the underlying mechanisms remain poorly understood. Inflammatory cytokine IL-17A is upregulated in PMO and plays vital roles in bone loss, but the upstream regulatory factors and mechanisms are still unknown.METHOD OF STUDY: Twenty PMO patients and 20 healthy control subjects were included to analyze IL-17A expression changes and screen dys-regulated miRNAs in the peripheral blood of PMO patients. miR-19a-5p mimics and inhibitor were transfected into RAW264.7 osteoclasts, and injected into bilateral ovariectomized (OVX) mice to explore the regulatory effect of miR-19a-5p on IL-17A. OVX mice were randomly grouped and treated with different doses of Hyp to uncover the effective targets for the medicine in PMO disease.RESULTS: MiR-19a-5p was downregulated in PMO patients and the expression level was negatively correlated with that of IL-17A. miR-19a-5p could directly bind to the 3'UTR of IL-17A and regulate its expression. Both in vitro and in vivo studies demonstrated that miR-19a-5p mimics decreased the expression of IL-17A, RANK and Cathepsin K, while miR-19a-5p inhibitor significantly increased the expression of IL-17A, RANK, and Cathepsin K. Importantly, the Hyp could improve bone structure of OVX mice by enhancing miR-19a-5p-mediated IL-17A downregulation.CONCLUSION: Overall, these data demonstrated that miR-19a-5p/IL-17A axis might serve as novel therapeutic candidate for PMO. Hyp could relieve bone resorption by targeting the miR-19a-5p/IL-17A axis in OVX mice and exhibited prospective for the treatment of PMO.

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PMID:  Food Funct. 2023 May 22 ;14(10):4734-4751. Epub 2023 May 22. PMID: 37114361 Abstract Title:  Development ofas functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems. Abstract:  Pharmacological activation of nuclear factor erythroid 2 related factor 2 (NRF2) provides protection against several environmental diseases by inhibiting oxidative and inflammatory injury. Besides high in protein and minerals,leaves contain several bioactive compounds, predominantly isothiocyanate moringin and polyphenols, which are potent inducers of NRF2. Hence,leaves represent a valuable food source that could be developed as a functional food for targeting NRF2 signaling. In the current study, we have developed a palatableleaf preparation (henceforth referred as ME-D) that showed reproducibly a high potential to activate NRF2. Treatment of BEAS-2B cells with ME-D significantly increased NRF2-regulated antioxidant genes (,) and total GSH levels. In the presence of brusatol (a NRF2 inhibitor), ME-D-induced increase in NQO1 expression was significantly diminished. Pre-treatment of cells with ME-D mitigated reactive oxygen species, lipid peroxidation and cytotoxicity induced by pro-oxidants. Furthermore, ME-D pre-treatment markedly inhibited nitric oxide production, secretory IL-6 and TNF-levels, and transcriptional expression of,, andin macrophages exposed to lipopolysaccharide. Biochemical profiling by LC-HRMS revealed glucomoringin, moringin, and several polyphenols in ME-D. Oral administration of ME-D significantly increased NRF2-regulated antioxidant genes in the small intestine, liver, and lungs. Lastly, prophylactic administration of ME-D significantly mitigated lung inflammation in mice exposed to particulate matter for 3-days or 3-months. In conclusion, we have developed a pharmacologically active standardized palatable preparation ofleaves as a functional food to activate NRF2 signaling, which can be consumed as a beverage (hot soup) or freeze-dried powder for reducing the risk from environmental respiratory disease.

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PMID:  Food Funct. 2023 May 11 ;14(9):4406-4413. Epub 2023 May 11. PMID: 37097224 Abstract Title:  Green tea intake and the risk of hypertension in premenopausal women: the TCLSIH cohort study. Abstract:  : Tea polyphenols, such as green tea polyphenols, have been extensively studied as agents that ameliorate cardiovascular disease and blood pressureand in animal studies. However, epidemiological evidence for the association of green tea consumption with hypertension (HTN) is inconsistent. In addition, such an association has not been prospectively examined in the general adult population, particularly among young women. Therefore, we designed a cohort study to examine whether green tea consumption increases the risk of HTN in premenopausal women.: This prospective cohort study investigated 6633 premenopausal female participants without hypertension, cardiovascular disease, and cancer at the baseline. Green tea consumption was measured at the baseline using a validated food frequency questionnaire. Hypertension was confirmed with the SBP140 mm Hgor with the DBP90 mm Hg. Cox proportional hazards regression models were used to examine the association of green tea consumption with incident hypertension. A total of 488 first incident cases of hypertension occurred during 24957 person-years of follow-up (median follow-up of 4.0 years). After adjustment for potential confounding variables, the multivariable hazard ratios (95% confidence intervals) for incident hypertension in premenopausal female participants with different green tea consumption frequencies were 1.00 (reference) for almost never, 0.84 (0.67, 1.07) for 1 cup per week, 1.02 (0.77, 1.35) for 2-6 cups per week, and 0.65 (0.44, 0.96) for1 cup per day.: The results from our prospective study indicate that the consumption of green tea is associated with a reduced risk of HTN in premenopausal women.

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PMID:  Food Funct. 2023 May 22 ;14(10):4456-4469. Epub 2023 May 22. PMID: 37066493 Abstract Title:  -Sitosterol protects against food allergic response in BALB/c mice by regulating the intestinal barrier function and reconstructing the gut microbiota structure. Abstract:  This study investigated whether-sitosterol has anti-allergic activity and explored its potential mechanism, using ovalbumin (OVA) allergic mouse model. Results indicated that supplementation with-sitosterol at 5-20 mg kgdayfor 7 weeks alleviated allergic symptoms and intestinal inflammation, and reduced serum OVA-specific immunoglobulin (Ig) E, IgG and histamine levels in sensitized mice.-Sitosterol enhanced physical and biochemical barrier in the intestinal epithelium by upregulating tight junction proteins (claudin-1, occludin, and ZO-1) expression and promoting the secretion of regenerating islet-derived protein IIIand secretory IgA in mucous layer. Furthermore,-sitosterol administration increased the levels of interleukin 10 and transforming growth factor-secreted by regulatory T cells, while reducing T helper 2 cell associated factor levels in intestinal lamina propria. Additionally, the alpha and beta diversity analysis revealed that the structure and diversity of the intestinal flora in the-sitosterol group tended to be normalized compared with the model group, and the number of biomarkers was reduced from 32 to 7. Moreover, the altered composition of gut microbiota in allergic mice was also reversed by-sitosterol supplementation, characterized by an increase in abundance ofandand a decrease in abundance of. Consequently,-sitosterol may prevent FA by ameliorating intestinal barrier function and remodeling the gut microbiota.

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PMID:  Food Funct. 2023 May 11 ;14(9):4117-4128. Epub 2023 May 11. PMID: 37039861 Abstract Title:  Marginal zinc deficiency alters the heart proteome of rats. Abstract:  Zinc deficiency is closely related to cardiovascular diseases (CVDs), but the effects of marginal zinc deficiency (MZD) after birth on the heart are unknown. In this study, 4-week-old male rats were fed a low zinc diet (10 mg kg, 1/3 recommended nutrient intake, RNI) for 8 weeks. Echocardiography and histopathology were performed to assess the functional and morphological alterations of the heart. High-throughput proteomics was used to study the effects of MZD on cardiac protein expression. We found that MZD reduced food intake, body weight, serum zinc, and heart weight; however, the coefficient, zinc concentration, function, and histopathology of the heart were not changed. The heart proteome was altered in the marginal zinc-deficient diet group (MZG), compared with the normal zinc diet group (NZG). A total of 310 differentially expressed proteins (

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PMID:  Food Funct. 2023 May 11 ;14(9):4129-4142. Epub 2023 May 11. PMID: 37042256 Abstract Title:  attenuates Coxsackievirus B3-induced pancreatitis through the BAX/BCL2/CASP3 signaling pathway. Abstract:  is a lactic acid bacterium widely used in food production. Coxsackievirus B3 (CVB3) is an important human pathogen associated with acute pancreatitis development, and no antiviral therapeutics or vaccines are approved to treat or prevent its infection. However, whethercould inhibit CVB3 infection remains unclear. Here,FLPL05 showed antiviral activity against CVB3 infectionand. Pretreatment withFLPL05 reduced serum amylase levels, CVB3 viral load in the pancreas, serum pro-inflammatory cytokine levels, and macrophage infiltration in CVB3-infected mice. In mice,FLPL05 inhibited CVB3-induced pancreas apoptosisthe B cell leukemia/lymphoma 2 (BCL2)/BCL2-associated X protein (BAX)/caspase-3 (CASP3) signaling pathway. Furthermore,FLPL05 reduced CVB3 replication, protected cells from the cytopathic effect of CVB3 infection, and inhibited cell apoptosis. Moreover,FLPL05's exopolysaccharide (EPS) had activity against CVB3, reducing the CVB3 titer and improving cell activity. Therefore,FLPL05 pretreatment improved CVB3-induced pancreatitis by partially reversing pancreatitis, which might be associated with EPS. Consequently,FLPL05 could be a potential probiotic with antiviral activity against CVB3.

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PMID:  Food Funct. 2023 Apr 24 ;14(8):3526-3537. Epub 2023 Apr 24. PMID: 37014333 Abstract Title:  Peptides from Antarctic krill () ameliorate acute liver injury in mice induced by carbon tetrachlorideactivating the Nrf2/HO-1 pathway. Abstract:  This study aimed to evaluate the hepatoprotective effects of peptides from Antarctic krill (AKP) on carbon tetrachloride (CCl)-induced acute liver injury (ALI) in mice and the underlying molecular mechanisms. ICR mice were pretreated with AKP (500 mg kg, i.g.) and silybin (30 mg kg, i.g.) for 15 days before CCl(0.25 mL per kg BW, i.p.) injection. To assess hepatocellular damage and molecular indices, the serum and liver tissue were evaluated at harvest. The results showed that AKP pretreatment remarkably attenuated CCl-induced liver injury, which was identified by the decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviation of hepatocyte necrosis, and inhibition of the levels of the pro-inflammatory factors TNF-and IL-1compared to those for silymarin. AKP pretreatment also enhanced the redox balance by reducing the concentrations of MDA and 8-iso-PG and increasing the activities of SOD, GSH and GSH-PX in the liver of mice. In addition, AKP upregulated oxidative stress-related mRNA expressions of Nrf2, Keap1, HO-1, and NQO1 and further activated the protein expression on the Nrf2/HO-1 singling pathway. In summary, AKP might be a promising hepatoprotective nutraceutical against ALI and its underlying mechanisms are associated with activation of the Nrf2/HO-1 pathway.

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PMID:  Biomedicines. 2023 Apr 1 ;11(4). Epub 2023 Apr 1. PMID: 37189686 Abstract Title:  Suppressive Effects ofon Depression through Regulating the Gut Microbiota and Metabolites in C57BL/6J Mice Induced by Ampicillin. Abstract:  Depression is a medical and social problem. Multiple metabolites and neuroinflammation regulate it. Modifying the gut microbiota with probiotics to reduce depression through the gut-brain axis is a potential treatment strategy. In this study, three anti-depressive potentials ofspp. (LAB), includingGMNL-74,GMNL-185 andGMNL-141, which combined to produce low dosage LAB (1.610CFU/mouse, LABL) and high dosage LAB (4.810CFU/mouse, LABH), were administered to C57BL/6 mice induced depression by ampicillin (Amp). A behavioral test of depression, 16S ribosomal RNA gene amplicon sequencing, bioinformatic analysis, and short-chain fatty acid (SCFA) content measurement were executed to investigate the gut microbiota composition, activation of nutrient metabolism pathways, levels of inflammatory factors, gut-derived 5-HT biosynthesis genes, and SCFA levels in C57BL/6 mice. Results showed that after mice were induced by Amp, both LAB groups recovered from depressive behaviors, decreased the abundance of, and increased the abundance ofandin the mouse ileum. The prediction of metabolism pathways of microbes revealed the activation of arginine and proline metabolism, cyanoamino acid metabolism, and nicotinate and nicotinamide metabolism were increased, and fatty acid synthesis was decreased in both LAB groups. The LABH groups showed increased levels of acetic acid, propanoic acid, and iso-butyric acid and decreased butyric acid levels in the cecum. LABH treatment increased claudin-5 and reduced IL-6 mRNA expression. Both LAB groups also reduced monoamine oxidase, and the LABH group increased vascular endothelial growth factor mRNA expression. These results showed that the composite of three LAB exerts antidepressant effects by regulating the gut microbiota and modifying the levels of depression-related metabolites in C57BL/6J Amp-treated mice.

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PMID:  Food Funct. 2023 May 11 ;14(9):3982-3993. Epub 2023 May 11. PMID: 36971096 Abstract Title:  ZJ316 alleviates ulcerative colitis by inhibiting inflammation and regulating short-chain fatty acid levels and the gut microbiota in a mouse model. Abstract:  Ulcerative colitis is an inflammatory bowel disease that is mainly related to gut microbiota dysbiosis.ZJ316 (ZJ316) has been proved to regulate the gut microbiota. However, more evidence is needed for the intestinal effects of ZJ316. Colitis was induceddissolved 2.5% DSS in drinking water for 7 days in 8-week-old BALB/c mice, which were then fed with ZJ316 (110CFU mL) for 35 days. After ZJ316 intervention, the dextran sulfate sodium salt (DSS)-induced colitis symptoms were remarkably alleviated, including recovery of body weight and colon weight and effective inhibition of the expression of pro-inflammatory cytokines. Results based on 16S rRNA gene sequencing indicated that the structure of the gut microbiota in ZJ316 supplementation was markedly altered by upregulating the percentage ofwhile reducing the percentage of. Furthermore, the colon contained more short-chain fatty acids (SCFAs) and butyrate-producing genera, such as,, and. Spearman correlation analysis indicated that SCFAs, especially butyric acid, were positively associated withandOur study suggested that ZJ316 could be used to relieve ulcerative colitis (UC) as dietary therapeutics.

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PMID:  Food Funct. 2023 Apr 24 ;14(8):3701-3711. Epub 2023 Apr 24. PMID: 36974730 Abstract Title:  The effect of ginger () supplementation on clinical, biochemical, and anthropometric parameters in patients with multiple sclerosis: a double-blind randomized controlled trial. Abstract:  : different lines of evidence have shown that ginger administration may be beneficial for patients with multiple sclerosis (MS). Therefore, we aimed to investigate the effect of ginger supplementation on disability, physical and psychological quality of life (QoL), body mass index (BMI), neurofilament light chain (NfL), interlukin-17 (IL-17), matrix metalloproteinase-9 (MMP-9), and neutrophil to lymphocyte ratio (NLR) in patients with relapsing-remitting MS.: this was a 12 week double-blind parallel randomized placebo-controlled trial with a 3 week run-in period. The treatment (= 26) and control (= 26) groups received 500 mg ginger and placebo (corn) supplements 3 times daily, respectively. Disability was evaluated using the Expanded Disability Status Scale (EDSS). QoL was rated using the Multiple Sclerosis Impact Scale (MSIS-29). BMI was calculated by dividing weight by height squared. Serum levels of NfL, IL-17, and MMP-9 were measured using the enzyme-linked immunosorbent assay. NLR was determined using a Sysmex XP-300automated hematology analyzer. All outcomes were assessed before and after the intervention and analyzed using the intention-to-treat principle.: in comparison with placebo, ginger supplementation caused a significant reduction in the EDSS (-0.540.580.080.23,

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PMID:  J Parasit Dis. 2023 Jun ;47(2):329-339. Epub 2023 Mar 25. PMID: 37193490 Abstract Title:  The potential therapeutic effect ofandextracts versus Nitazoxanide drug against experimentally induced cryptosporidiosis in laboratory mice. Abstract:  In this study, the potential anti-cryptosporidial effect of(black seeds) and(ginger) alcoholic extracts versus Nitazoxanide (NTZ) medication was investigated in immunosuppressed (IS) laboratory mice. Parasitological, histopathological studies were used to assess their therapeutic efficacy. Serum level and tissue expression percentage of IFN-was also used. Nigella extract succeeded to reduce the mean oocyst counts in the feces of immunosuppressed mice followed by NTZ. Ginger-treated ones showed the lowest reduction percentage.showed the best results in terms of restoring the normal architecture of ileal epithelium in histopathological sections stained with H&E. NTZ treatment sub-groups showed mild improvement, followed by ginger-treated mice, which showed a slight improvement in small intestine microenvironment. A significant substantial rise in serum and intestinal tissue IFN-cytokine levels were recorded in Nigella subgroups compared to those of NTZ and ginger respectively. According to our findingsoutperformed Nitazoxanide in terms of anti-cryptosporidial effectiveness and regeneration characteristics revealing a promising medication. When compared to the commonly used Nitazoxanide medication or Nigella extracts, the outcomes of ginger extract were suboptimal.

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PMID:  Neurochem Res. 2023 Sep ;48(9):2826-2834. Epub 2023 May 6. PMID: 37148458 Abstract Title:  Effects of Curcumin on Axon Growth and Myelin Sheath Formation in an In Vitro Model. Abstract:  Although the beneficial effects of curcumin, extracted from rhizomes of the ginger family genus Curcuma, on the repair and regeneration of nerves have been evaluated in vitro, there are few studies concerning its effects on axon myelination. Here, we used pheochromocytoma cells as an in vitro model of peripheral nerves. Pheochromocytoma cells were cultured alone or cocultured with Schwann cells and treated with increasing concentrations of curcumin. Cell growth was observed, and the expression levels of growth-associated protein 43 (GAP-43), microtubule-associated protein 2 (MAP-2), myelin basic protein (MBP), myelin protein zero (MPZ), Krox-20, and octamer binding factor 6 (Oct-6) were quantified. We found a significant increase in expression of all six proteins following curcumin treatment, with a corresponding increase in the levels of MBP, MPZ, Krox-20, and Oct-6 mRNA. Upregulation was greater with increasing curcumin concentration, showing a concentration-dependent effect. The results suggested that curcumin can promote the growth of axons by upregulating the expression of GAP-43 and MAP-2, stimulate synthesis and secretion of myelin-related proteins, and facilitate formation of the myelin sheath in axons by upregulating the expression of Krox-20 and Oct-6. Therefore, curcumin could be widely applied in future strategies for the treatment of nerve injuries.

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PMID:  Photochem Photobiol Sci. 2023 Apr 19. Epub 2023 Apr 19. PMID: 37076760 Abstract Title:  Protective effect and mechanism research of Phyllanthus emblica Linn. fruit extract on UV-induced photodamage in keratinocytes. Abstract:  Ultraviolet (UV) irradiation causes acute and chronic cutaneous effects that may result in photodamage and photoaging. Epidermis keratinocytes, as the closest surface of skin, are susceptible to damage from UV rays. Phyllanthus emblica Linn. fruit (PE) extract, as a medicine and food dual-use plant, contains high levels of polyphenols and possesses multiple pharmacological properties. The present study investigated common and different molecular mechanisms and signaling pathway activations of UVA and UVB stimulated cell damage and photoprotective effect of PE extract against UVA and UVB by Methyl Thiazolyl Tetrazolium (MTT) method, Elisa assay, flow cytometry, differentially expressed genes analysis and western blot analysis. The results showed that UVA exposure (10 J/cm) reduced HaCaT cell viability significantly, increased the apoptosis rate, elevated intracellular reactive oxygen species level and reduced antioxidant enzyme activities. And UVA irradiation could inhibit the ERK/TGF-/Smad signaling pathway to downregulate collagen I, collagen III and elastin expressions, resulting in the photoaging of skin cells. We also found UVB exposure (30 mJ/cm) caused HaCaT cell damage, promoted apoptosis, increased ROS production and induced the release of proinflammatory cytokines (IL-1, IL-6 and PGE2). Further, in HaCaT cells, UVB ray was able to induce the activation of apoptosis markers (cleaved PARP1 and cleaved caspase3) through the MAPK/AP-1 signaling pathway using western blot analysis. Pre-treatment of PE extract prevented the UVA and UVB induced photoaging and injury in HaCaT cells through activation of ERK/TGF-/Smad pathway and inhibition of MAPK/AP-1 pathway, respectively. Therefore, PE extract has the potential to be used as an oral and topical preparation against skin aging and injury induced by UVA and UVB.

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PMID:  Food Funct. 2023 Apr 24 ;14(8):3406-3422. Epub 2023 Apr 24. PMID: 36974511 Abstract Title:  Meta-analysis of randomized controlled trials of the effects of probiotics in Parkinson's disease. Abstract:  : Patients with Parkinson's disease (PD) demonstrate intestinal dysbiosis and substantial gastrointestinal dysfunction. Preliminary evidence suggests that probiotics may have a positive effect on the motor and non-motor symptoms of PD. However, the effectiveness of probiotics in treating PD remains unclear. Therefore, a randomized controlled trial (RCT) was performed to examine the efficacy of oral probiotics in PD treatment.: PubMed, Web of Science, Cochrane Library, EMBASE, Clinical Trials, and Google Scholar were searched for relevant RCTs published until January 28, 2023. Meta-analyses have examined the effects of probiotics on motor and non-motor symptom parameters in RCTs. Inverse-variance random or fixed effects were used to pool data. The Grading of Recommendations Assessment, Development, and Evaluations was used to examine the quality of evidence for outcomes of the meta-analysis.: Nine eligible RCTs (= 663) were included in this meta-analysis. In the meta-analysis, probiotic treatment significantly improved motor symptoms (UPDRS-III scores: standardized mean difference [SMD] = -0.28, 95% confidence interval [CI], -0.49 to -0.07,= 7%), constipation and constipation-related quality of life (Bristol scores: SMD = 0.54; 95% CI, 0.35 to 0.73,= 0%; bowel movement scores: SMD = 0.83; 95% CI, 0.59 to 1.07,= 43%; CSBMs: SMD = 0.56; 95% CI, 0.30 to 0.82,= 0%; PAC-QCL scores: SMD = -0.84; 95% CI, -1.08 to -0.60,= 0%), and anxiety and depression parameters (HAMA scores: SMD = -0.35; 95% CI, -0.60 to -0.10,= 0%; HADM-17 scores: SMD = -0.33; 95% CI, -0.59 to -0.08,= 0%). In addition, probiotic supplements significantly reduced the use of laxatives (SMD = -0.27; 95% CI, -0.53 to -0.01,= 15%) and increased GSH levels in the serum of PD patients (SMD = 0.52; 95% CI, 0.14 to 0.90,= 0%). The certainty of evidence was graded as very low for UPDRS-III, PAC-QCL, CSBMs, HAMA, HADM-17 and Bristol scores and low for bowel movement scores. Two of the nine RCTs reported that probiotics may cause abdominal bloating at low rates on consuming probiotics, which suggests that we should pay attention to the occurrence of adverse events during the consumption of probiotics in future studies.: Oral probiotic consumption significantly improved motor symptoms, gastrointestinal dysfunction, anxiety, and depression in patients with PD. Notably, oral probiotics also reduced the use of laxatives and increased GSH levels in the serum of patients with PD. In future studies, more high-quality evidence from large-scale RCTs is needed to determine the exact effects of probiotic treatment on PD....

PMID:  Exp Ther Med. 2023 Jun ;25(6):265. Epub 2023 Apr 20. PMID: 37206558 Abstract Title:  Sulforaphane alleviates lung ischemiareperfusion injury through activating Nrf2/HO1 signaling. Abstract:  Oxidative stress and inflammation are both involved in the pathogenesis of lung ischemia-reperfusion (I/R) injury. Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant properties. The present study hypothesized that SFN may protect against lung I/R injury via the regulation of antioxidant and anti-inflammatory-related pathways. A rat model of lung I/R injury was established, and rats were randomly divided into 3 groups: Sham group, I/R group, and SFN group. It was shown that SFN protected against a pathological inflammatory response via inhibition of neutrophil accumulation and in the reduction of the serum levels of the pro-inflammatory cytokines, IL-6, IL-1, and TNF-. SFN treatment also significantly inhibited lung reactive oxygen species production, decreased the levels of 8-OH-dG and malondialdehyde, and reversed the decrease in the antioxidant activities of the enzymes catalase, superoxide dismutase, and glutathione peroxidase in the lungs of the I/R treated rats. In addition, SFN ameliorated I/R-induced lung apoptosis in rats by suppressing Bax and cleaved caspase-3 levels and increased Bcl-2 expression. Furthermore, SFN treatment activated an Nrf2-related antioxidant pathway, as indicated by the increased nuclear transfer of Nrf2 and the downstream HO-1 and NADPH quinone oxidoreductase-1. In conclusion, these findings suggested that SFN protected against I/R-induced lung lesions in rats via activation of the Nrf2/HO-1 pathway and the accompanied anti-inflammatory and anti-apoptotic effects.

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PMID:  Biomedicines. 2023 Mar 23 ;11(4). Epub 2023 Mar 23. PMID: 37189614 Abstract Title:  Sulforaphane-Induced Cell Mitotic Delay and Inhibited Cell Proliferation via Regulating CDK5R1 Upregulation in Breast Cancer Cell Lines. Abstract:  Our research has revealed that sulforaphane (SFN) has chemopreventive properties and could be used in chemotherapy treatments. Further investigation is needed to understand the mechanisms behind sulforaphane's (SFN) antitumor activity in breast adenocarcinoma, as observed in our studies. This research looked into the effects of SFN on mitosis delay and cell cycle progression in MDA-MB-231 and ZR-75-1 cells, two types of triple-negative breast cancer adenocarcinoma.The proliferation of the cancer cells after SFN exposure was evaluated using MTT assay, DNA content and cell cycle arrest induction by flow cytometry, and expressions of cdc25c, CDK1, cyclin B1 and CDK5R1 were assessed through qRT-PCR and Western blot analysis. SFN was found to inhibit the growth of cancer cells. The accumulation of G2/M-phase cells in SFN-treated cells was attributed to CDK5R1. The disruption of the CDC2/cyclin B1 complex suggested that SFN may have antitumor effects on established breast adenocarcinoma cells. Our findings suggest that, in addition to its chemopreventive properties, SFN could be used as an anticancer agent for breast cancer, as it was found to inhibit growth and induce apoptosis of cancer cells.

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PMID:  Food Sci Nutr. 2023 May ;11(5):2277-2287. Epub 2023 Mar 31. PMID: 37181316 Abstract Title:  Effects of sulforaphane on breast cancer based on metabolome and microbiome. Abstract:  Sulforaphane (SFN) is a promising phytochemical with a wide range of antitumor activities. A comprehensive understanding of the effects of SFN on breast cancer based on the metabolome and microbiome is limited. Thus, we treated MCF-7 cell-transplanted nude mice with 50mg/kg SFN. SFN inhibits breast cancer cell proliferation. SFN increased the levels of sulfate-related metabolites and glutathione-related metabolites and decreased tryptophan metabolites and methyl-purine metabolites in urinary metabolic profile. SFN indirectly affected the activation of aryl hydrocarbon receptor by tryptophan metabolism. The ratio of SAM to methionine was decreased by SFN while the global DNA methylation was downregulated in tumor tissue. SFN decreased the sulfate-reducing bacterium, which is related to reduced methylation capacity, and increased the genusrelated to tryptophan metabolites with antitumor activities. In conclusion, we provide a perspective on the metabolome and microbiome to elucidate the antitumor activities of SFN.

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PMID:  Food Funct. 2023 Apr 3 ;14(7):3259-3268. Epub 2023 Apr 3. PMID: 36928268 Abstract Title:  F40-4 ameliorates hyperuricemia by modulating the gut microbiota and alleviating inflammation in mice. Abstract:  Hyperuricemia (HUA) is a systemic disease characterized by a disorder of purine metabolism and an abnormal increase in the serum level of uric acid (UA). Probiotics can exert potential therapeutic benefits against some metabolic diseases by regulating the intestinal microbiota.F40-4 with UA-lowering activity of 87.40% was screened using purine as the target. The UA-lowering activity ofF40-4 was further explored in a mouse model of HUA.F40-4 could downregulate serum levels of UA, blood urea nitrogen, creatinine, and xanthine oxidase by 40.84%, 11.61%, 57.66%, and 41.79%, respectively.F40-4 restored organ damage, and adjusted enzyme activity and transporter expression to promote the metabolic level of UA. In addition,F40-4 could reshape the gut microbiota and suppress inflammation to ameliorate HUA. An increment in intestinal UA excretion was documented. These findings suggest thatF40-4 might serve as a potential probiotic for the prevention and treatment of HUA.

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PMID:  Food Funct. 2023 Mar 20 ;14(6):2668-2683. Epub 2023 Mar 20. PMID: 36883322 Abstract Title:  Oolong tea of different years protects high-fat diet-fed mice against obesity by regulating lipid metabolism and modulating the gut microbiota. Abstract:  Long-term stored oolong tea has recently attracted considerable attention concerning its salutary effect. In this study, the anti-obesity effect of different years' oolong tea on high-fat diet-fed mice was compared. Wuyi rock tea of 2001, 2011, and 2020 were chosen to be the representative samples of oolong tea. The results showed that eight-week administration of 2001 Wuyi rock tea (WRT01), 2011 Wuyi rock tea (WRT11), and 2020 Wuyi rock tea (WRT20) extracts (400 mg per kg per d) significantly decreased the body weight and attenuated the obesity in high-fat diet-fed mice. 2001 and 2011 Wuyi rock teas reduced obesity mainly through regulating lipid metabolism and activating the AMPK/SREBP-1 pathway, downregulating the expression of SREBP-1, FAS, and ACC and upregulating CPT-1a expression; while the 2011 and 2020 Wuyi rock teas by moderating the gut microbiota dysbiosis, reshaping the gut microbiota, and promoting the growth of beneficial bacteria, especially. 2011 Wuyi rock tea was proven to be more effective in reducing body weight gain and liver oxidative stress than the others. Collectively, all three Wuyi rock teas of different years alleviated high-fat diet-induced obesity by regulating lipid metabolism and modulating gut microbiota, whereas the emphasis of their internal mechanism is different with different storage ages.

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PMID:  Molecules. 2022 Nov 6 ;27(21). Epub 2022 Nov 6. PMID: 36364431 Abstract Title:  Green Tea Catechins Attenuate Neurodegenerative Diseases and Cognitive Deficits. Abstract:  Neurodegenerative diseases exert an overwhelming socioeconomic burden all around the globe. They are mainly characterized by modified protein accumulation that might trigger various biological responses, including oxidative stress, inflammation, regulation of signaling pathways, and excitotoxicity. These disorders have been widely studied during the last decade in the hopes of developing symptom-oriented therapeutics. However, no definitive cure has yet been discovered. Tea is one of the world's most popular beverages. The same plant,(L.).O. Kuntze, is used to make green, black, and oolong teas. Green tea has been most thoroughly studied because of its anti-cancer, anti-obesity, antidiabetic, anti-inflammatory, and neuroprotective properties. The beneficial effect of consumption of tea on neurodegenerative disorders has been reported in several human interventional and observational studies. The polyphenolic compounds found in green tea, known as catechins, have been demonstrated to have many therapeutic effects. They can help in preventing and, somehow, treating neurodegenerative diseases. Catechins show anti-inflammatory as well as antioxidant effects via blocking cytokines' excessive production and inflammatory pathways, as well as chelating metal ions and free radical scavenging. They may inhibit tau protein phosphorylation, amyloid beta aggregation, and release of apoptotic proteins. They can also lower alpha-synuclein levels and boost dopamine levels. All these factors have the potential to affect neurodegenerative disorders. This review will examine catechins' neuroprotective effects by highlighting their biological, pharmacological, antioxidant, and metal chelation abilities, with a focus on their ability to activate diverse cellular pathways in the brain. This review also points out the mechanisms of catechins in various neurodegenerative and cognitive diseases, including Alzheimer's, Parkinson's, multiple sclerosis, and cognitive deficit.

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PMID:  Food Funct. 2023 Mar 20 ;14(6):2857-2869. Epub 2023 Mar 20. PMID: 36880662 Abstract Title:  Natural isoflavone formononetin inhibits IgE-mediated mast cell activation and allergic inflammation by increasing IgE receptor degradation. Abstract:  Immunoglobulin (Ig)E-associated mast cell (MC) activation triggers pro-inflammatory signals that underlie type I allergic diseases. Here, we examined the effects of the natural isoflavone formononetin (FNT) on IgE-mediated MC activation and associated mechanisms of high-affinity IgE receptor (FcRI) signal inhibition. The effects of FNT on the mRNA expression of inflammatory factors, release of histamine and-hexosaminidase (-hex), and expression of signaling proteins and ubiquitin (Ub)-specific proteases (USPs) were analyzed in two sensitized/stimulated MC lines. FcRI-USP interactions were detected by co-immunoprecipitation (IP). FNT dose-dependently inhibited-hex activity, histamine release, and inflammatory cytokine expression in FcRI-activated MCs. FNT suppressed IgE-induced NF-B and MAPK activity in MCs. The oral administration of FNT attenuated passive cutaneous anaphylaxis (PCA) reactions and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) reactions in mice. FNT reduced the FcRIchain expression,increased proteasome-mediated degradation, and induced FcRIubiquitination by inhibiting USP5 and/or USP13. FNT and USP inhibition may be useful for suppressing IgE-mediated allergic diseases.

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PMID:  Phytother Res. 2023 Jun ;37(6):2693-2737. Epub 2023 May 17. PMID: 37195042 Abstract Title:  Molecular mechanisms underlying the potential neuroprotective effects of Trifolium pratense and its phytoestrogen-isoflavones in neurodegenerative disorders. Abstract:  Neurodegenerative disorders are heterogeneous, debilitating, and incurable groups of brain disorders that have common features including progressive degeneration of the structure and function of the nervous system. Phytoestogenic-isoflavones have been identified as active compounds that can modulate different molecular signaling pathways related to the nervous system. The main aim is to shed the light on the molecular mechanisms followed by phytoestrogen-isoflavones profound in the Trifolium pratense and discuss the latest pharmacological findings in the treatment of neurodegenerative disorders. Data were collected using different databases. The search terms used included "Phytoestrogens," "Isoflavones," "neurodegenerative disorders," "Neuronal plasticity," etc., and combinations of these keywords. As a result, this review article mainly demonstrates the potential neuroprotective properties of phystoestrogen-isoflavones present in the Trifolium pratense (Red clover), particularly in neurodegenerative disorders. Phytochemical studies have shown that Trifolium pratense mainly includes more than 30 isoflavone compounds. Among them, phytoestrogen-isoflavones, such as biochanin A, daidzein, formononetin, genistein (Gen), etc.,are characterized by potent neuroprotective properties against different neurodegenerative disorders. There are preclinical and clinical scientific evidence on their mechanisms of action involve molecular interaction with estrogenic receptors, anti-inflammatory, anti-oxidative, antiapoptotic, autophagic inducing, and so on. phytoestrogen-isoflavones are the major bioactive components in the Trifolium pratense that exhibit therapeutic efficacy in the case of neurodegenerative disorders. This review provides detailed molecular mechanisms targeted by phytoestrogen-isoflavones and experimental key findings for the clinical use of prescriptions containing Trifolium pratense-derived isoflavones for the treatment of neurodegenerative disorders.

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PMID:  Immunol Invest. 2023 Nov ;52(4):399-414. Epub 2023 Mar 28. PMID: 36975047 Abstract Title:  Formononetin Inhibits Microglial Inflammatory Response and Contributes to Spinal Cord Injury Repair by Targeting the EGFR/MAPK Pathway. Abstract:  Zhenbao Pill contains many Chinese herbal medicinal ingredients and has been proven to have therapeutic effects on the repair of spinal cord injury (SCI). This study attempts to investigate the role of formononetin (FMN), an ingredient of Zhenbao Pill, in regulating neuroinflammation after SCI and the underlying mechanism. Primary microglia isolated from the spinal cord of newborn rats and human microglial clone 3 (HMC3) cells were stimulated with IL-1followed by FMN incubation. The cell viability and inflammatory cytokine levels were detected. The target of FMN was predicted and screened using databases. By silencing or overexpression of epidermal growth factor receptor (EGFR), the anti-neuroinflammatory effect of FMN was assessed in vitro. In vivo, FMN was intraperitoneally injected into rats after SCI followed by the neurological function and histopathology examination. The isolated microglia were in high purity, and the different concentrations of FMN incubation had no toxic effects on primary microglia and HMC3 cells. FMN reduced the inflammatory cytokine levels (TNF-and IL-6) in a concentration-dependent manner. EGFR silencing or FMN incubation decreased p-EGFR and p-p38 levels and down-regulated inflammatory cytokine levels in IL-1-stimulated cells or supernatants. Nevertheless, the effects of FMN on microglial inflammation were reversed by EGFR overexpression. In vivo, FMN treatment improved the neuromotor function, repaired tissue injury, and inhibited EGFR/p38MAPK phosphorylation. Formononetin inhibits microglial inflammatory response and contributes to SCI repair via the EGFR/p38MAPK signaling pathway.

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PMID:  Phytother Res. 2023 Apr 1. Epub 2023 Apr 1. PMID: 37002905 Abstract Title:  Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF-kB and MAPK signaling pathways. Abstract:  Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-B ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-B signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1, FMN inhibited the NF-B signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.

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PMID:  Life Sci. 2023 Feb 15 ;315:121331. Epub 2022 Dec 29. PMID: 36586573 Abstract Title:  Formononetin ameliorates ferroptosis-associated fibrosis in renal tubular epithelial cells and in mice with chronic kidney disease by suppressing the Smad3/ATF3/SLC7A11 signaling. Abstract:  AIMS: Chronic kidney disease (CKD) is characterized by interstitial fibrosis, while limited treatment drugs are available. Ferroptosis is a newly identified process that can trigger tubular atrophy and fibrosis. The aim of this study is to investigate the effects of formononetin (FN), a bioflavonoid, on ferroptosis and renal fibrosis.MAIN METHODS: In vivo experiments, unilateral ureteral obstruction (UUO)- and folic acid (FA, 250 mg/kg)-induced CKD models were constructed in C57BL/6 mice of 6-8 weeks old, followed by the administration with 40 mg/kg/day FN by gavage. For in vitro experiments, ferroptosis was induced with RSL3 or erastin in primary mouse renal tubular epithelial cells (TECs), followed by the addition of indicated concentrations of FN. Then, the levels of ferroptosis and fibrosis were analyzed. The translocation of Smad3, ATF3, and Nrf2 from the cytoplasm to the nucleus was checked by western blotting. The interaction of Smad3 and ATF3 was detected by Co-immunoprecipitation.KEY FINDINGS: FN dramatically ameliorated tubular injury along with reduced expression of the profibrotic genes including-SMA, Col1a1, and fibronectin in both two CKD mouse models and RSL3/erastin-treated TECs. Furthermore, FN administration also significantly suppressed ferroptosis, as evidenced by increased expression of SLC7A11 and GPX4, and decreased levels of 4-HNE. In mechanism, FN disrupted the interaction between Smad3 and ATF3, resulting in the blocking of their translocation from the cytoplasm to the nucleus. In addition, FN also promoted the separation of the Nrf2/Keap1 complex and enhanced Nrf2 nuclear accumulation.SIGNIFICANCE: FN alleviates CKD by impeding ferroptosis-associated fibrosis by suppressing the Smad3/ATF3/SLC7A11 signaling and could serve as a candidate therapeutic drug for CKD.

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PMID:  Microbiol Spectr. 2023 Jun 15 ;11(3):e0052623. Epub 2023 May 16. PMID: 37191530 Abstract Title:  Perillaldehyde Functions as a Potential Antifungal Agent by Triggering Metacaspase-Independent Apoptosis in Botrytis cinerea. Abstract:  Botrytis cinerea, the causal agent of gray mold, is an important plant pathogen causing preharvest and postharvest diseases. Due to the extensive use of commercial fungicides, fungicide-resistant strains have emerged. Natural compounds with antifungal properties are widely present in various kinds of organisms. Perillaldehyde (PA), derived from the plant species Perilla frutescens, is generally recognized as a potent antimicrobial substance and to be safe to humans and the environment. In this study, we demonstrated that PA could significantly inhibit the mycelial growth of B. cinerea and reduced its pathogenicity on tomato leaves. We also found that PA had a significant protective effect on tomato, grape, and strawberry. The antifungal mechanism of PA was investigated by measuring the reactive oxygen species (ROS) accumulation, the intracellular Calevel, the mitochondrial membrane potential, DNA fragmentation, and phosphatidylserine exposure. Further analyses revealed that PA promoted protein ubiquitination and induced autophagic activities and then triggered protein degradation. When the two metacaspase genes,and, were knocked out from, all mutants did not exhibit reduced sensitivity to PA. These findings demonstrated that PA could induce metacaspase-independent apoptosis in. Based on our results, we proposed that PA could be used as an effective control agent for gray mold management.Botrytis cinerea causes gray mold disease, is considered one of the most important dangerous pathogens worldwide, and leads to severe economic losses worldwide. Due to the lack of resistant varieties of, gray mold control has mainly relied on application of synthetic fungicides. However, long-term and extensive use of synthetic fungicides has increased fungicide resistance inand is harmful to humans and the environment. In this study, we found that perillaldehyde has a significant protective effect on tomato, grape, and strawberry. We further characterized the antifungal mechanism of PA on. Our results indicated that PA induced apoptosis that was independent of metacaspase function.

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PMID:  Molecules. 2023 Apr 12 ;28(8). Epub 2023 Apr 12. PMID: 37110648 Abstract Title:  An Ethanol Extract ofLeaves Suppresses Adrenergic Agonist-Induced Metastatic Ability of Cancer Cells by Inhibiting Src-Mediated EMT. Abstract:  Previous studies have indicated that the adrenergic receptor signaling pathway plays a fundamental role in chronic stress-induced cancer metastasis. In this study, we investigated whether an ethanol extract ofleaves (EPF) traditionally used to treat stress-related symptoms by moving Qi could regulate the adrenergic agonist-induced metastatic ability of cancer cells. Our results show that adrenergic agonists including norepinephrine (NE), epinephrine (E), and isoproterenol (ISO) increased migration and invasion of MDA-MB-231 human breast cancer cells and Hep3B human hepatocellular carcinoma cells. However, such increases were completely abrogated by EPF treatment. E/NE induced downregulation of E-cadherin and upregulation of N-cadherin, Snail, and Slug. Such effects were clearly reversed by pretreatment with EPF, suggesting that the antimetastatic activity of EPF could be related to epithelial-mesenchymal transition (EMT) regulation. EPF suppressed E/NE-stimulated Src phosphorylation. Inhibition of Src kinase activity with dasatinib completely suppressed the E/NE-induced EMT process. Transfecting MDA-MB-231 cells with constitutively activated Src (SrcY527F) diminished the antimigration effect of EPF. Taken together, our results demonstrate that EPF can suppress the adrenergic agonist-promoted metastatic ability of cancer cells by inhibiting Src-mediated EMT. This study provides basic evidence supporting the probable use of EPF to prevent metastasis in cancer patients, especially those under chronic stress.

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PMID:  Front Pharmacol. 2023 ;14:1114410. Epub 2023 Mar 14. PMID: 36998613 Abstract Title:  Efficacy of(L.) Britton var.extract on mild knee joint pain: A randomized controlled trial. Abstract:  This study aimed to evaluate the clinical efficacy and safety of PE extracts developed for the purpose of relieving pain and improving knee joint function on semi-healthy people with mild knee joint pain.A randomized, double-blind, two-arm, single-center, placebo-controlled clinical trial was conducted. Individuals with knee joint pain and a visual analogue scale (VAS) score

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PMID:  Front Pharmacol. 2023 ;14:1044576. Epub 2023 Apr 18. PMID: 37144216 Abstract Title:  Lycium barbarum polysaccharide alleviates dextran sodium sulfate-induced inflammatory bowel disease by regulating M1/M2 macrophage polarization via the STAT1 and STAT6 pathways. Abstract:  Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal, which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways.

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PMID:  Free Radic Biol Med. 2023 Aug 1 ;204:84-94. Epub 2023 Apr 28. PMID: 37119863 Abstract Title:  Lycium barbarum polysaccharide-glycoprotein ameliorates ionizing radiation-induced epithelial injury by regulating oxidative stress and ferroptosis via the Nrf2 pathway. Abstract:  Radiation-induced oral mucositis (RIOM) is considered to be the most common acute side effect of radiation therapy and occurs during intentional or accidental radiation exposure. Antioxidant synthesis agents have been reported to protect against or alleviate the development of mucositis, but the resulting side effects of chemical synthesis agents limit their use in clinical practice. Lycium barbarum polysaccharide-glycoprotein (LBP), a polysaccharide extract of the Lycium barbarum fruit, has superior antioxidant capacity and biosafety and is a potential option for radiation prevention and treatment. Here, we aimed to investigate whether LBP conferred radioprotection against ionizing radiation-induced oral mucosal damage. We found that LBP exerted radioprotective effects in irradiated HaCaT cells, improving cell viability, stabilizing mitochondrial membrane potential, and decreasing cell death. LBP pretreatment reduced oxidative stress and ferroptosis in radioactivity-damaged cells by activating the transcription factor Nrf2 and promoting its downstream targets, such as HO-1, NQO1, SLC7A11, and FTH1. Knockdown of Nrf2 eliminated the protective effects of LBP, implying the essential role of Nrf2 in LBP activity. Additionally, the topical application of LBP thermosensitive hydrogel on rat mucosa resulted in a significant decrease in ulcer size in the irradiated group, suggesting that LBP oral mucoadhesive gel may be a potential tool for the treatment of irradiation. In conclusion, we demonstrated that LBP attenuates ionizing radiation-induced oral mucosa injury by reducing oxidative stress and inhibiting ferroptosis via the Nrf2 signaling pathway. LBP may be a promising medical countermeasure against RIOM.

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PMID:  Foods. 2023 Apr 11 ;12(8). Epub 2023 Apr 11. PMID: 37107413 Abstract Title:  Oligosaccharides Alleviate Hepatic Steatosis by Modulating Gut Microbiota in C57BL/6J Mice Fed a High-Fat Diet. Abstract:  High-fat diets (HFD) can promote the development of hepatic steatosis by altering the structure and composition of gut flora. In this study, the potential therapeutic mechanism ofoligosaccharide (LBO) against hepatic steatosis was investigated by analyzing the changes in the intestinal flora and metabolites in mice. Mice on an HFD were administered LBO by gavage once daily for a continuous period of eight weeks. Compared with the HFD group, the levels of triglyceride (TG), alanine aminotransferase (ALT) in the serum, and hepatic TG were significantly reduced in the LBO group, and liver lipid accumulation was obviously improved. In addition, LBO could regulate the HFD-induced alteration of intestinal flora. The HFD increased the proportion of,, and. LBO increased the proportion of,, and. LBO also altered the fecal metabolic profile. Significantly different metabolites between LBO and the HFD, such as taurochenodeoxycholate, taurocholate, fluvastatin, and kynurenic acid, were related to the cholesterol metabolism, bile acid metabolism, and tryptophan metabolic pathways. In light of the above, LBO can alleviate HFD-induced NAFLD by modulating the components of the intestinal flora and fecal metabolites.

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PMID:  Food Funct. 2023 Mar 20 ;14(6):2768-2780. Epub 2023 Mar 20. PMID: 36857703 Abstract Title:  Cherry juice alleviates high-fat diet-induced obesity in C57BL/6J mice by resolving gut microbiota dysbiosis and regulating microRNA. Abstract:  Cherry is a nutrient-rich food that is good for health. This study demonstrated the inhibitory action of dietary cherry juice on high-fat diet (HFD)-induced obesity in mice. Cherry juice intervention significantly decreased body weight, fat contents, and blood lipid levels in obese mice. The overproduction of proinflammatory cytokines was suppressed by dietary cherry juice, which was accompanied by the elevation of tight junction proteins to maintain intestinal barrier. Moreover, dietary cherry juice restored the decreased production of short-chain fatty acids (SCFAs) by regulating the composition and abundance of gut microbiota. In addition, dietary cherry juice also suppressed the expression of some microRNAs associated with obesity such as miR-200c-3p, miR-125a-5p, miR-132-3p, and miR-223-3p and target proteins related with microRNAs in the inguinal or epididymal white tissue in the obese mice. These results offer a fresh perspective on cherry juice's role in the prevention of obesity caused by the HFD.

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