SIRT1: Harnessing multiple pathways to hinder NAFLD

Pharmacological Research, Год журнала: 2024, Номер 203, С. 107155 - 107155

Опубликована: Март 23, 2024

Non-alcoholic fatty liver disease (NAFLD) encompasses hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. It is the primary cause of chronic disorders, with a high prevalence but no approved treatment. Therefore, it indispensable to find trustworthy therapy for NAFLD. Recently, mounting evidence illustrates that Sirtuin 1 (SIRT1) strongly associated SIRT1 activation or overexpression attenuate NAFLD, while deficiency aggravates Besides, an array therapeutic agents, including natural compounds, synthetic traditional Chinese medicine formula, stem cell transplantation, alleviates NALFD via upregulation. Mechanically, NAFLD by reestablishing autophagy, enhancing mitochondrial function, suppressing oxidative stress, coordinating lipid metabolism, as well reducing hepatocyte apoptosis inflammation. In this review, we introduced structure function briefly, summarized effect on its mechanism, along application agonists in treating

Язык: Английский

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(±)-Hypandrone A, a pair of polycyclic polyprenylated acylphloroglucinol enantiomers with a caged 7/6/5/6/6 pentacyclic skeleton from Hypericum androsaemum

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(12), С. 3459 - 3464

Опубликована: Янв. 1, 2024

(±)-Hypandrone A (1), a pair of highly modified PPAP enantiomers, with an unprecedented caged 2,8,17-trioxapentacyclo-[11.4.2.0 1,9 .0 4,9 10,15 ]-nonadecane core, were isolated from the fruits Hypericum androsaemum .

Язык: Английский

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Platelet‐derived apoptotic vesicles ameliorate nonalcoholic fatty liver disease by regulating lipid metabolism via apolipoprotein A‐II

Deleted Journal, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Abstract Nonalcoholic fatty liver disease (NAFLD) encompasses a broad range of conditions, commencing with simple steatosis and progressing to non‐alcoholic steatohepatitis, the possibility further deterioration into fibrosis, cirrhosis, ultimately, hepatocellular carcinoma. Unfortunately, there is currently no approved medication for treating NAFLD‐associated steatosis. This underscores need improved therapeutic approaches that can modulate lipid metabolism halt transition from chronic disease. Our previous studies have demonstrated apoptotic vesicles (apoVs), which are produced during apoptosis, show great potential in regulating homeostasis. However, whether they ameliorate NAFLD unknown. In our research, apoVs derived platelets (PLT‐apoVs) as well mesenchymal stem cells (MSC‐apoVs) were used treat NAFLD. The results showed PLT‐apoVs exhibited superior effects diminishing accumulation induced by high‐fat diet than MSC‐apoVs. Through proteomic analysis, we defined validated apolipoprotein A‐II (APOA2) regulator apoV‐mediated MSC adipogenesis, could be target enhance apoV biomedical field. Owing higher expression APOA2, better pave way apoV‐based therapy

Язык: Английский

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Berberine directly targets AKR1B10 protein to modulate lipid and glucose metabolism disorders in NAFLD

Journal of Ethnopharmacology, Год журнала: 2024, Номер 332, С. 118354 - 118354

Опубликована: Май 17, 2024

Язык: Английский

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LC-HRMS profiling of Dendrobium huoshanense aqueous extract and its therapeutic effects on nonalcoholic fatty liver disease in mice through the TLR2-NF-κB and AMPK-SREBP1-SIRT1 signaling pathways

Journal of Chromatography B, Год журнала: 2025, Номер unknown, С. 124563 - 124563

Опубликована: Март 1, 2025

Язык: Английский

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Linghe Granules Reduces Hepatic Lipid Accumulation in Non-Alcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Redox Balance

Phytomedicine, Год журнала: 2025, Номер 141, С. 156654 - 156654

Опубликована: Апрель 2, 2025

Язык: Английский

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Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(3), С. 2320 - 2342

Опубликована: Март 11, 2024

Rare ginsenoside compound K (CK) is an intestinal microbial metabolite with a low natural abundance that primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns field of ginseng research and development, as well ginsenoside-related dietary supplements products. Ginsenosides Rb1, Rb2, Rc are generally used substrate generate via several bioconversion processes. Current shows wide range pharmacological actions, including boosting osteogenesis, lipid glucose metabolism, oxidation, insulin resistance, anti-inflammatory anti-apoptosis properties. Further on bioavailability toxicology can advance its medicinal application. The purpose this review lay groundwork for future clinical studies development therapy disorders. Furthermore, pharmacology investigated review. findings indicate modulates signaling pathways associated AMPK, SIRT1, PPARs, WNTs, NF-kB. It also demonstrates positive therapeutic effect non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia, diabetes, complications, osteoporosis. Additionally, analogues showed more bioavailability, less toxicity, efficacy against states. Enhancing regulating hazardous variables crucial use trials.

Язык: Английский

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Silymarin decreases liver stiffness associated with gut microbiota in patients with metabolic dysfunction-associated steatotic liver disease: a randomized, double-blind, placebo-controlled trial

Lipids in Health and Disease, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 3, 2024

Despite centuries of traditional use silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability highlights possible influence gut microbiota silymarin; however, no human have investigated this aspect. To determine potential efficacy improving MASLD indicators to investigate underlying mechanisms related microbiota. In 24-week randomized, double-blind, placebo-controlled trial, 83 patients with were either placebo (n = 41) or (103.2 mg/d, n 42). At 0, 12, 24 weeks, stiffness hepatic steatosis assessed using FibroScan, blood samples gathered biochemical detection, while faecal collected at 0 weeks 16S rRNA sequencing. Silymarin supplementation significantly reduced (LSM, -0.21 ± 0.17 vs. 0.41 0.17, P 0.015) serum levels γ-glutamyl transpeptidase (GGT, -8.21 3.01 1.23 3.16, 0.042) ApoB (-0.02 0.03 0.07 0.03, 0.023) but had significant effect attenuation parameter (CAP), other (aminotransferases, total bilirubin, glucose lipid parameters, hsCRP, SOD, UA), physical measurements (DBP, SBP, BMI, WHR, BF%, BMR), APRI FIB-4 indices. Gut analysis revealed increased species diversity enrichment Oscillospiraceae group. These findings suggest that could improve patients, possibly by modulating was registered Chinese Clinical Trial Registry (ChiCTR2200059043).

Язык: Английский

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Silybin A from Silybum marianum reprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids

Theranostics, Год журнала: 2025, Номер 15(5), С. 2006 - 2034

Опубликована: Янв. 6, 2025

Rationale:Silybum marianum is used to protect against degenerative liver damage. The molecular mechanisms of its bioactive component, silybin, remained enigmatic, although membrane-stabilizing properties, modulation membrane protein function, and metabolic regulation have been discussed for decades. Methods: Experiments were performed with hepatocyte cell lines primary monocytes in vitro under both basal stressed conditions, mice vivo. Quantitative lipidomics was detect changes phospholipids triglycerides. Key findings confirmed by Western blotting, quantitative PCR, microscopy, enzyme activity assays, flux studies, functional relationships investigated using selective inhibitors. Results: We show that specifically the stereoisomer silybin A decreases triglyceride levels lipid droplet content, while enriching major phospholipid classes maintaining a homeostatic composition human hepatocytes mouse vivo normal pre-disease conditions. Conversely, cell-based disease models overload lipotoxic stress, treatment primarily depletes Mechanistically, silymarin/silybin suppresses phospholipid-degrading enzymes, induces biosynthesis varying degrees depending on down-regulates remodeling/biosynthesis, inducing complex sterol fatty acid metabolism. Structure-activity relationship studies highlight importance 1,4-benzodioxane ring configuration reduction saturated 2,3-bond flavanonol moiety accumulation. Enrichment hepatic intracellular expansion are associated heightened biotransformation capacity. Conclusion: Our study deciphers structural features contributing remodeling suggests protects individuals mild dysregulation, involving class switch from triglycerides phospholipids, whereas it may be less effective states severe dysregulation.

Язык: Английский

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Bioactive Small Compounds Effectively Inhibit ChREBP Overexpression to Treat NAFLD and T2DM: A Computational Drug Development Approach

Heliyon, Год журнала: 2025, Номер 11(4), С. e42477 - e42477

Опубликована: Фев. 1, 2025

A glucose-dependent carbohydrate-signaling gene regulator named Carbohydrate response element binding protein (ChREBP), has recently been discovered as a major metabolic of enzymes involved in the progression non-alcoholic fatty liver disease (NAFLD) and type-II diabetes mellitus (T2DM). As result, this research is aimed to identify natural small molecules drug candidates that target ChREBP order counter aggressive NAFLD T2DM. comprehensive silico design strategy was implemented find possible inhibitors targeted protein. site-specific molecular docking approach used screen 20 FDA approved anti-diabetic drugs 494 phytochemicals from sources against ChREBP, top ten compounds were selected for further studies based on their affinities. The ADME toxicity profiles demonstrated efficacy safety. result MD simulations protein–ligand complex structures indicated stability potential activity. data screening process following docking, ADMET properties, simulation approaches, five (dieckol, isocorilagin, stachyurin, stachysetin thonningianin A) with favorable values which indicates strong promising effective treatment T2DM.Graphical abstract

Язык: Английский

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