Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 30(3)

Published: Oct. 30, 2023

Abstract Background Gemfibrozil (Gem) is a drug that has been shown to activate PPAR‐α, nuclear receptor plays key role in regulating lipid metabolism. Gem used lower the levels of triglycerides and reduce risk coronary heart disease patients. Experimental studies vitro vivo have can prevent or slow progression neurological disorders (NDs), including cerebral ischemia (CI), Alzheimer's (AD), Parkinson's (PD), multiple sclerosis (MS). Neuroinflammation known play significant these disorders. Method The literature review for this study was conducted by searching Scopus, Science Direct, PubMed, Google Scholar databases. Result results show neuroprotective effects through several cellular molecular mechanisms such as: (1) ability upregulate pro‐survival factors (PGC‐1α TFAM), promoting survival function mitochondria brain, (2) strongly inhibits activation NF‐κB, AP‐1, C/EBPβ cytokine‐stimulated astroglial cells, which are increase expression iNOS production NO response proinflammatory cytokines, (3) protects dopamine neurons MPTP mouse model PD increasing PPARα, turn stimulates GDNF astrocytes, (4) reduces amyloid plaque pathology, activity glial improves memory, (5) increases myelin genes (MBP CNPase) via PPAR‐β, (6) hippocampal BDNF counteract depression. Conclusion According study, investigated its potential therapeutic effect NDs. Further research needed fully understand

Language: Английский

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Lactobacillus Casei-fermented Amomum Xanthioides Mitigates non-alcoholic fatty liver disease in a high-fat diet mice model

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116250 - 116250

Published: Feb. 5, 2024

Non-alcoholic fatty liver disease (NAFLD) is a substantial global health issue owing to its high prevalence and the lack of effective therapies. Fermentation medicinal herbs has always been considered feasible strategy for enhancing efficacy in treating various ailments. This study aimed investigate potential benefits Lactobacillus casei-fermented Amomum xanthioides (LAX) on NAFLD high-fat diet model. HFD-fed C57BL6/j mice were administered with 200 mg/kg LAX or unfermented (AX) 100 metformin 6 weeks from 4th week. The 10-week HFD-induced alterations hepatic lipid accumulation inflammation significantly attenuated by dominantly (more than AX metformin), which evidenced pathohistological findings, contents, inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)− IL-1β, oxidative parameters such as reactive oxygen species (ROS) malondialdehyde (MDA), molecular changes reversely between lipogenic proteins glycerol-3-phosphate acyltransferase (GPAM) sterol regulatory element-binding protein (SREBP)− 1, lipolytic peroxisome proliferator-activated receptor (PPAR-α) AMP-activated kinase (AMPK)-α tissues. In addition, abnormal serum (triglyceride, total cholesterol LDL-cholesterol) notably ameliorated LAX. conclusion, these findings support promising plant-derived remedy NAFLD.

Language: Английский

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Endoplasmic reticulum stress PERK-ATF4-CHOP pathway is involved in non-alcoholic fatty liver disease in type 1 diabetic rats: The rescue effect of treatment exercise and insulin-like growth factor I

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e27225 - e27225

Published: March 1, 2024

Endoplasmic Reticulum Stress (ERS) is a key factor in the development of Non-Alcoholic Fatty Liver Disease (NAFLD) diabetes. The current study aimed to examine effects exercise and IGF-I on ERS markers liver tissue. Rats were divided into five groups (n = 8 per group), including control (CON), diabetes (DIA), + (DIA EX), IGF-I), EX IGF-I). Type 1 was induced by an I.P. injection streptozotocin (60 mg/kg). After 30 days treatment with or alone combination, tissue assessed for caspase 12, 8, CHOP protein levels, expression (ATF-6, PERK, IRE-1A) lipid metabolism-involved genes (FAS, FXR, SREBP-1c) western immunoblotting. In addition, evaluation histopathological changes liver, Hematoxylin - Eosin Masson's Trichrome staining done. Compared group, significantly caused fibrosis, ERS, increased 12 levels changed associated metabolism, FAS, SREBP-1c. Treatment either reduced fibrosis suppressed ER stress apoptosis, improved metabolism. simultaneous showed synergistic effect compared DIA E IGF-I. results suggest that IGF-1 possibly reducing creating adaptive status, improving folding.

Language: Английский

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Epigenetics of alcohol-related liver diseases

JHEP Reports, Journal Year: 2022, Volume and Issue: 4(5), P. 100466 - 100466

Published: March 10, 2022

Alcohol-related liver disease (ARLD) is a primary cause of chronic in the United States. Despite advances diagnosis and management ARLD, it remains major public health problem associated with significant morbidity mortality, emphasising need to adopt novel approaches study ARLD its complications. Epigenetic changes are increasingly being recognised as contributing pathogenesis multiple states. Harnessing power innovative technologies for epigenetics (e.g., next-generation sequencing, DNA methylation assays, histone modification profiling computational techniques like machine learning) has resulted seismic shift our understanding pathophysiology ARLD. Knowledge these paramount importance practicing hepatologist researchers alike. Accordingly, this review article we will summarise current knowledge about alcohol-induced epigenetic alterations context including but not limited to, hyper/hypo methylation, modifications, non-coding RNA, 3D chromatin architecture enhancer-promoter interactions. Additionally, discuss state-of-the-art used (e.g. single-cell sequencing). We also highlight regulation chemokines their proinflammatory role Lastly, examine clinical applications

Language: Английский

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Curcumin-loaded chitosan nanoparticles alleviate fenpropathrin-induced hepatotoxicity by regulating lipogenesis and pyroptosis in rats

Food and Chemical Toxicology, Journal Year: 2023, Volume and Issue: 180, P. 114036 - 114036

Published: Sept. 13, 2023

Language: Английский

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Bisphenol A induced hepatic steatosis by disturbing bile acid metabolism and FXR/TGR5 signaling pathways via remodeling the gut microbiota in CD-1 mice

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 889, P. 164307 - 164307

Published: May 20, 2023

Language: Английский

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Nobiletin Intake Attenuates Hepatic Lipid Profiling and Oxidative Stress in HFD-Induced Nonalcoholic-Fatty-Liver-Disease Mice

Molecules, Journal Year: 2023, Volume and Issue: 28(6), P. 2570 - 2570

Published: March 12, 2023

Nobiletin (NOB) is a naturally occurring compound, commonly found in citrus peel, that shows hepatoprotective and lipid-reducing effects. However, the lipid biomarkers potential improvement mechanisms have not been adequately explored. Therefore, we investigated ameliorative effect molecular mechanism of NOB on NAFLD induced by high-fat diet mice. The results showed supplementation with over 12 weeks markedly improved glucose tolerance, serum profiles, inflammatory factors, hepatic steatosis, oxidative stress. These beneficial effects were mainly related to reduced levels including free fatty acids, diacylglycerols, triacylglycerols, cholesteryl esters according lipidomic analysis. Twenty lipids, DGs phosphatidylcholines, identified as biomarkers. Furthermore, RT-qPCR Western blot analysis indicated inhibited expression lipogenesis-related factors such SREBP-1c, SCD-1, FAS, upregulated oxidation (PPARα) cholesterol conversion (LXRα, CYP7A1, CYP27A1) genes well antioxidation-related (Nucl-Nrf2, NQO1, HO-1, GCLC), indicating intake may reduce biosynthesis increase consumption improve steatosis This study for understanding NAFLD.

Language: Английский

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Biological Role and Related Natural Products of SIRT1 in Nonalcoholic Fatty Liver

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2023, Volume and Issue: Volume 16, P. 4043 - 4064

Published: Dec. 1, 2023

Abstract: Non-alcoholic fatty liver disease(NAFLD) is an umbrella term for a range of diseases ranging from hepatic fat accumulation and steatosis to non-alcoholic steatohepatitis (NASH) in the absence excessive alcohol consumption other definite damage factors. The incidence NAFLD has increased significantly recent years will continue grow coming decades. become huge health problem economic burden. SIRT1 member Sirtuins, group highly conserved histone deacetylases regulated by NAD+, plays vital role regulating cholesterol lipid metabolism, improving oxidative stress, inflammation, insulin resistance through deacetylating some downstream transcription factors thus NAFLD. Although there are no currently approved drugs treating unresolved limitations developing activators, holds promise as proper therapeutic target metabolic diseases. In years, natural products have played increasingly important drug development due their safety efficacy. It been discovered that may be able prevent treat targeting its related pathways. This paper reviews mechanism improvement NALFD regulate associated pathways, discusses potential effectiveness these clinical or dietary supplements. These works provide new ideas directions finding targets anti-NAFLD with good pharmacodynamic properties. Keywords: NAFLD, SIRT1, products, FFA, TG

Language: Английский

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Acacetin Protects against Non-Alcoholic Fatty Liver Disease by Regulating Lipid Accumulation and Inflammation in Mice

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4687 - 4687

Published: April 23, 2022

We previously demonstrated that acacetin reduces adipogenesis in adipocytes, and decreases lipid accumulation visceral adipocyte tissue. Here we investigated whether regulated the mechanisms of lipogenesis inflammation non-alcoholic fatty liver disease (NAFLD) obese mice. Male C57BL/6 mice were fed a high-fat diet (HFD), then administered by intraperitoneal injection. Acacetin reduced body weight Acacetin-treated exhibited decreased accumulation, increased glycogen improved hepatocyte steatosis. triglycerides total cholesterol serum. low-density lipoprotein leptin concentrations, but high-density adiponectin levels effectively weakened gene expressions transcription factors related to lipogenesis, promoted genes lipolysis acid β-oxidation liver. also inflammation-related cytokines serum Oleic induced murine FL83B hepatocytes, effects treatment indicated may regulate metabolism through AMPK pathway. protect against hepatic steatosis modulating expression.

Language: Английский

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Omega-3 fatty acids and metabolic partitioning of fatty acids within the liver in the context of nonalcoholic fatty liver disease

Current Opinion in Clinical Nutrition & Metabolic Care, Journal Year: 2022, Volume and Issue: 25(4), P. 248 - 255

Published: June 28, 2022

Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent form of globally, affecting about 25% world's adult population. It more common in those living with obesity, where it may affect as many 80% individuals. The aim this article to describe recent human studies evaluating influence omega-3 acids on de novo lipogenesis (DNL) and hepatic acid partitioning between incorporation into triacylglycerols (TAGs) β-oxidation, discuss relevance these effects context NAFLD, provide an overview mechanisms that might be involved.The eicosapentaenoic (EPA) docosahexaenoic (DHA) decrease DNL partition away from TAG synthesis toward β-oxidation. EPA DHA multiple transcription factors resulting down-regulation pathway upregulation net result decreased accumulation lowering circulating concentrations. Human trials demonstrate can fat patients NAFLD.Increased intake reduce likelihood could used NAFLD.

Language: Английский

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