Ethanol extract of Polygonatum cyrtonema Hua mitigates non-alcoholic steatohepatitis in mice

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 30, 2025

Background Polygonum cyrtonema Hua is a kind of traditional Chinese botanic drug. Modern pharmacological research has confirmed that able to alleviate nonalcoholic fatty liver disease, but the precise mechanism requires further investigation. This study investigated protective effects and underlying mechanisms Polygonatum ethanol extract (PCE) against Non-alcoholic steatohepatitis (NASH) in mice. Methods UHPLC-MS/MS was utilized analyze metabolites PCE. The NASH mouse model establishment C57BL/6J mice via high-fat diet (HFD) feeding for 12 weeks, from 9th week, were gavaged with PCE (100, 300, 900 mg/kg/day), simvastatin (4 mg/kg) or saline. One hand, injury assessed by serum enzymes, biochemistry, histopathology; On other RNA-seq, qPCR, Western blot employed investigate related molecular mechanisms. Results 211 identified through analysis. ameliorated HFD induced improved hepatocellular degeneration steatosis dose-dependent way. restored expression AMPK, SIRT1, SREBP1 PPAR-α both mRNA protein levels. RNAseq unique gene profiles response compared treatments. HFD-induced DEGs attenuated abolished following Ingenuity pathway analysis RNA-seq data revealed key canonical pathways upstream molecules regulated Conclusion Our findings confirm ability alleviating underscores AMPK/SIRT1 as potential theraputic target treatment.

Language: Английский

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Advances in the Regulation of Growth by SIRT1

Medical Diagnosis, Journal Year: 2025, Volume and Issue: 15(01), P. 22 - 27

Published: Jan. 1, 2025

Language: Английский

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A comparative genomic study across 396 liver biopsies provides deep insight into FGF21 mode of action as a therapeutic agent in metabolic dysfunction‐associated steatotic liver disease

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

Language: Английский

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Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging

Biogerontology, Journal Year: 2025, Volume and Issue: 26(2)

Published: Feb. 26, 2025

Language: Английский

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Puerarin prevents cadmium-induced endoplasmic reticulum stress via SIRT1-dependent PERK‒CHOP pathway in HepG2 cells

Acta Biochimica et Biophysica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Cadmium (Cd) is a high-risk heavy metal that induces oxidative stress, endoplasmic reticulum (ER) stress and inflammation, damaging organs such as the liver. Puerarin (PUE) has been shown to treat liver injury especially prevent Cd-induced hepatic damage via its antioxidant activity. Sirtuin 1 (SIRT1), histone deacetylase, key protector against various insults. However, role in protection of PUE not clarified. Thus, this study designed elucidate molecular mechanism human hepatoma cell line HepG2. The results first reveal apoptosis significantly restored by pretreatment, confirmed CCK-8, flow cytometric, Hoechst 33258 TUNEL assays. Mechanistically, decreases ROS production increases SOD levels Cd-treated HepG2 cells. Moreover, pretreatment alleviates ER inhibiting PERK-eIF2α-ATF4-CHOP axis subsequently partially restores function revealed decreased Ca²⁺ release from ER. In addition, further demonstrates upregulates SIRT1 expression, which suppresses PERK signaling cascade reduces CHOP levels. Collectively, our demonstrate protects cells at least pathway expression-dependent manner. appears have great potential hepatoprotective agent.

Language: Английский

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Linking epidemiology and genomics of maternal smoking during pregnancy in utero and in ageing: a population-based study using human foetuses and the UK Biobank cohort

EBioMedicine, Journal Year: 2025, Volume and Issue: unknown, P. 105590 - 105590

Published: March 1, 2025

SummaryBackgroundMaternal smoking and foetal exposure to nicotine other harmful chemicals in utero remains a serious public health issue with little knowledge about the underlying genetics consequences of maternal ageing individuals. Here, we investigated epidemiology genomic architecture middle-aged population compare results effects observed developing foetus.MethodsIn current project, included 351,562 participants from UK Biobank (UKB) estimated status during pregnancy through self-reporting UKB mother's around their birth. In addition, analysed 64 liver transcriptomic expression datasets collected women seeking elective terminations. Foetal was confirmed measurement plasma cotinine levels.FindingsFoetal had greater impact on males than females, more differentially expressed genes tissue (3313 vs. 1163) higher pathway activation. UKB, linked an unhealthy lifestyle, lower education, damage. genome-wide analysis leveraged shared genetic basis between affected offspring mothers identified five significant regions. We found low heritability trait (∼4%) implicated several disease-related transcriptome-wide association study. Maternal increased all-cause mortality risk (Hazard ratio 95% CI: 1.10 [1.04; 1.16], P = 4.04 × 10−4), which attenuated non-smoking males.InterpretationAlthough male foetuses are females by pregnancy, this effect largely reduced Importantly, our highlight that overall 10% due greatly non-smokers. This study demonstrates importance campaigns promoting prevention families where parent(s) smoke.FundingFunding for project provided University Aberdeen, Science Initiative Panel Institute Medical Science, Research Council, Seventh Framework Programme European Union under Grant Agreement 212885 (REEF) NHS Grampian Endowments grants.

Language: Английский

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Sirtuins and Gut Microbiota: Dynamics in Health and a Journey from Metabolic Dysfunction to Hepatocellular Carcinoma

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 466 - 466

Published: March 20, 2025

Metabolic dysfunction leading to non-alcoholic fatty liver disease (NAFLD) exhibits distinct molecular and immune signatures that are influenced by factors like gut microbiota. The microbiome interacts with the via a bidirectional relationship gut–liver axis. Microbial metabolites, sirtuins, responses pivotal in different metabolic diseases. This extensive review explores complex multifaceted interrelationship between sirtuins microbiota, highlighting their importance health disease, particularly hepatocellular carcinoma (HCC). Sirtuins (SIRTs), classified as group of NAD+-dependent deacetylases, serve crucial modulators wide spectrum cellular functions, including pathways, inflammatory response, process senescence. Their subcellular localization diverse functions link them various conditions, NAFLD cancer. Concurrently, comprising microorganisms, significantly influences host metabolism responses. Recent findings indicate modulate microbiota composition function, while can affect sirtuin activity. is relevant disorders, where dysbiosis contributes progression. highlights recent on roles specific maintaining implications HCC development. Understanding these interactions offers potential therapeutic avenues for managing diseases linked dysregulation pathology.

Language: Английский

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Glutathionylation and Metabolic Dysfunction-associated Steatotic Liver Disease

Biochimie, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Efficacy and mechanism of action of Yanxiao Di’naer formula for non-alcoholic steatohepatitis treatment based on metabolomics and RNA sequencing

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 333, P. 118487 - 118487

Published: June 24, 2024

Language: Английский

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Elevated mir‐141 in obesity: Insights into the interplay with sirtuin 1 and non‐alcoholic fatty liver disease

Obesity Science & Practice, Journal Year: 2024, Volume and Issue: 10(5)

Published: Sept. 27, 2024

Abstract Background Changes in gene expression related to obesity are linked microRNAs, such as miR‐141, which play a crucial role metabolic homeostasis. Sirtuin 1 (SIRT1), an enzyme that plays regulating various cellular functions and metabolism, is implicated the ensuing non‐alcoholic fatty liver disease (NAFLD). The aim of this research was evaluate levels miR‐141 its relationship with SIRT1 NAFLD. Methods A group 100 adults (50 50 normal‐weight) were selected underwent complete clinical evaluation anthropometric measurements. Biochemical parameters assessed blood serum, plasma measured by real‐time PCR. also evaluated peripheral mononuclear cells using Real‐time ELISA technique used determine insulin levels. Liver steatosis ultrasound. Results results showed significantly increased participants compared control group. Conversely, individuals lower than participants. strong negative correlation observed between positive association parameters. Furthermore, had elevated gene, those without liver. Conclusion might be contributing factor repression consequences, including Therefore, serve suitable diagnostic therapeutic target

Language: Английский

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