Fisetin Ameliorates Alcohol-Induced Liver Injury through Regulating SIRT1 and SphK1 Pathway

The American Journal of Chinese Medicine, Journal Year: 2022, Volume and Issue: 50(08), P. 2171 - 2184

Published: Jan. 1, 2022

Alcoholic liver disease (ALD) often leads to hepatitis, hepatic cirrhosis, and even hepatocellular carcinoma. Fisetin has been shown confer protection against injury. Herein, we investigated whether fisetin could prevent ethanol-induced hepatotoxicity. Mice were fed on 5% (v/v) Lieber-DeCarli ethanol diet. Human primary stellate cells (HSCs) co-cultured with used verify the therapeutic effect of fisetin. The results alanine/aspartate aminotransferase (ALT/AST), Triglyceride (TG), total cholesterol (TC) in serum, Oil O Red Masson staining revealed that (80[Formula: see text]mg/kg) ameliorated mice injury fibrosis. Besides, immunofluorescence [Formula: text]-SMA suppressed HSCs activation. suppression was dose-dependent. Furthermore, promoted SIRT1-mediated autophagy inhibited Sphk1-mediated endoplasmic reticulum stress (ER stress) both vitro vivo. Molecular docking indicated potential interaction SIRT1 SphK1. inhibitory activation reversed co-culturing EX-527, a specific inhibitor STIR1 overexpression. Thus, ameliorate alcohol-induced through activation, ER stress.

Language: Английский

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The metabolic and toxic acute effects of phloretin in the rat liver

Chemico-Biological Interactions, Journal Year: 2022, Volume and Issue: 364, P. 110054 - 110054

Published: July 22, 2022

Language: Английский

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Therapeutic Effects of Heterotrigona itama (Stingless Bee) Bee Bread in Improving Hepatic Lipid Metabolism through the Activation of the Keap1/Nrf2 Signaling Pathway in an Obese Rat Model

Antioxidants, Journal Year: 2022, Volume and Issue: 11(11), P. 2190 - 2190

Published: Nov. 5, 2022

Bee bread (BB) has traditionally been used as a dietary supplement to treat liver problems. This study evaluated the therapeutic effects of Heterotrigona itama BB from Malaysia on obesity-induced hepatic lipid metabolism disorder via regulation Keap1/Nrf2 pathway. Male Sprague Dawley rats were fed with either normal diet or high-fat (HFD) for 6 weeks induce obesity. Following weeks, obese treated distilled water (OB group), (0.5 g/kg body weight/day) + group) orlistat (10 mg/kg OR concurrent HFD another weeks. treatment suppressed Keap1 and promoted Nrf2 cytoplasmic nuclear translocations, leading reduction in oxidative stress, antioxidant enzyme activities liver. Furthermore, down-regulated synthesis its regulator levels (SIRT1, AMPK), up-regulated fatty acid β-oxidation rats, being consistent alleviated levels, improved histopathological changes (steatosis, hepatocellular hypertrophy, inflammation glycogen expression) prevented progression non-alcoholic steatohepatitis. These results showed potentials H. against stress possibly by targeting pathway, hence proposing role natural capable treating disease.

Language: Английский

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Phloretamide Prevent Hepatic and Pancreatic Damage in Diabetic Male Rats by Modulating Nrf2 and NF-κB

Nutrients, Journal Year: 2023, Volume and Issue: 15(6), P. 1456 - 1456

Published: March 17, 2023

This study examined the effect of phloretamide, a metabolite phloretin, on liver damage and steatosis in streptozotocin-induced diabetes mellitus (DM) rats. Adult male rats were divided into two groups: control (nondiabetic) STZ-treated rats, each which was further treated orally with vehicle phloretamide 100 mg or 200 mg. Treatments conducted for 12 weeks. Phloretamide, at both doses, significantly attenuated STZ-mediated pancreatic β-cell damage, reduced fasting glucose, stimulated insulin levels It also increased hexokinase, coincided significant reduction glucose-6 phosphatase (G-6-Pase), fructose-1,6-bisphosphatase 1 (PBP1) livers these diabetic Concomitantly, doses hepatic serum triglycerides (TGs) cholesterol (CHOL), low-density lipoprotein (LDL-c), ballooning. Furthermore, they lipid peroxidation, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), mRNA, total nuclear NF-κB p65, but mRNA levels, Nrf2, as well glutathione (GSH), superoxide dismutase (SOD-1), catalase (CAT), heme-oxygenase-1 (HO-1) All effects dose-dependent. In conclusion, is novel drug that could ameliorate DM-associated via its powerful antioxidant anti-inflammatory effects. Mechanisms protection involve improving structure action, suppressing NF-κB, stimulating Nrf2.

Language: Английский

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Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 7, 2023

The importance of gut-liver axis in the pathophysiology metabolic dysfunction-associated fatty liver disease (MAFLD) is being investigated more closely recent times. However, inevitable changes gut microbiota during progression merits closer look. present work intends to assess time-dependent dysbiosis MAFLD, its implications and role plant-derived prebiotics attenuation. Male C57BL/6J mice were given western diet (WD) for up 16 weeks phloretin was administered orally. fecal samples collected every fourth week weeks. animals sacrificed at end study biochemical histological analyses performed. Further, 16S rRNA amplicon sequencing analysis performed investigate longitudinal modification microbiome different time points. Findings our corroborate that alleviated mitigated circulating inflammatory cytokines levels. Phloretin treatment resists WD induced microbial diversity decreased endotoxin content. Prolonged exposure changed dynamics abundance distribution. Increased pathogenic taxa like Desulfovibrionaceae, Peptostreptococcus, Clostridium, Terrisporobacter noted. not only reversed this but also modulated taxonomic signatures beneficial microbes Ruminococcus, Lactobacillus, Alloprevotella. Therefore, potential restore eubiosis could be utilized as an intervention strategy prevention MAFLD related disorders.

Language: Английский

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