Hormetic Nutrition and Redox Regulation in Gut–Brain Axis Disorders

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 484 - 484

Published: April 18, 2024

The antioxidant and anti-inflammatory effects of hormetic nutrition for enhancing stress resilience overall human health have received much attention. Recently, the gut-brain axis has attracted prominent interest preventing therapeutically impacting neuropathologies gastrointestinal diseases. Polyphenols polyphenol-combined nanoparticles in synergy with probiotics shown to improve gut bioavailability blood-brain barrier (BBB) permeability, thus inhibiting oxidative stress, metabolic dysfunction inflammation linked dysbiosis ultimately onset progression central nervous system (CNS) disorders. In accordance hormesis, polyphenols display biphasic dose-response by activating at a low dose Nrf2 pathway resulting upregulation

Language: Английский

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SIRT1: Harnessing multiple pathways to hinder NAFLD

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107155 - 107155

Published: March 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

Language: Английский

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Polystyrene nanoplastics exposure triggers spermatogenic cell senescence via the Sirt1/ROS axis

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 279, P. 116461 - 116461

Published: May 19, 2024

Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat reproductive health. However, exact effects of PS-NPs exposure on testicular cells underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with (80 nm) at different dosages (0, 10, 40 mg/kg/day) for 60 days, GC-1 treated this study. Enlarged seminiferous tubule lumens loose vacuolated layer spermatogenic observed PS-NPs-exposed mice. Spermatogenic which may be one target damage, decreased from group. caused undergo senescence, manifested as elevated SA-β-galactosidase activity activated senescence-related signaling p53-p21/Rb-p16 pathways, induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested key role reactive oxygen species (ROS) PS-NPs-induced result was confirmed by measuring ROS levels. Moreover, inhibition partially attenuated senescence phenotype DNA damage. Using health atlas (MHA) database, Sirt1 filtrated critical molecule regulation senescence. overexpression main generator Nox2, downregulated Sirt1, increased p53 acetylated vivo vitro, whereas these disturbances restored pterostilbene. In addition, pterostilbene intervention significantly alleviated burst. Collectively, our study reveals that can trigger mediated regulating Sirt1/ROS axis. Importantly, promising strategy alleviate

Language: Английский

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Sirtuin activators as an anti-aging intervention for longevity

Published: Jan. 12, 2025

Sirtuins are a family of NAD+-dependent class III histone deacetylases that regulate histones and other proteins. The mammalian sirtuins comprise seven members have role in energy metabolism, DNA repair, inflammation, cell survival, apoptosis, cellular senescence, oxidative stress, mitochondrial production. Sirtuin modulation may beneficial effects on aging age-related diseases; thus, attracting growing interest discovering small molecules modifying their activity. A compounds both natural chemically synthesized has emerged as sirtuin activators. This review discusses aging, the activate sirtuins, activity, its impact alleviating aging.

Language: Английский

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SIRT1/DNMT3B-mediated epigenetic gene silencing in response to phytoestrogens in mammary epithelial cells

Epigenetics, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 3, 2025

We performed an integrated analysis of genome-wide DNA methylation and expression datasets in normal cells healthy animals exposed to polyphenols with estrogenic activity (i.e. phytoestrogens). identified that phytoestrogens target genes linked disrupted cellular homeostasis, e.g. limiting break repair (RNF169) or promoting ribosomal biogenesis (rDNA). Existing evidence suggests may be governed by sirtuin 1 (SIRT1) deacetylase via interactions methylating enzymes, specifically DNMT3B. Since SIRT1 was reported regulated phytoestrogens, we test whether suppress related homeostasis SIRT1/DNMT3B-mediated transcriptional silencing. Human MCF10A mammary epithelial were treated pterostilbene (PTS) genistein (GEN), followed cell growth, methylation, gene expression, SIRT1/DNMT3B binding. occupancy at the selected phytoestrogen-target genes, RNF169 rDNA, accompanied consistent promoter hypermethylation downregulation response GEN, but not PTS. GEN-mediated binding a robust DNMT3B enrichment rDNA promoters. This observed PTS, suggesting distinct mechanism action. Although both bind promoters upon two proteins do co-occupy regions. Depletion abolishes decrease SIRT1-dependent epigenetic suppression GEN. These findings enhance our understanding role SIRT1-DNMT3B interplay mechanisms mediating impact on biology homeostasis.

Language: Английский

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The Anti-Cancer Role of Pterostilbene in Endometrial Cancer: A Phase II Prospective, Randomized, Window-of-Opportunity Clinical Trial with Megestrol Acetate

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 345 - 345

Published: March 14, 2025

Pterostilbene (3,5-dimethoxy-40-hydroxystilbene) is a potent oral antioxidant with promising role in anti-cancer treatment. In endometrial cancer (EC), vitro studies demonstrated synergistic antiproliferative effect of pterostilbene (PT) megestrol acetate (MA), common treatment for EC. This randomized phase II clinical trial (NCT03671811) PT+MA vs. MA three weeks prior to scheduled hysterectomy. The primary objective determine the using Ki-67 index. secondary objectives are toxicity, histological response, transcriptional changes, and lipid metabolism. A total 44 patients were enrolled between January 2019 November 2022 23 Arm 1 (PT+MA) 21 2 (MA). Toxicities included one G3 thromboembolic event hypertension Histological responses high both arms (>90%). There was no difference although, when restricted endometroid subtype, relative decrease Ki67 33.8% 20.1% alone (p = 0.14). Whole transcriptomic gene profiling samples before after exposure activation interferon alpha response pathway suppression mTORC1 signaling, hypoxia, oxidative phosphorylation, IL2-STAT5 signaling. Lipid metabolism analyses did not reveal any significant changes arms. PT well-tolerated preoperative EC vivo effects on level.

Language: Английский

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Miquelianin in Folium Nelumbinis extract promotes white-to-beige fat conversion via blocking AMPK/DRP1/mitophagy and modulating gut microbiota in HFD-fed mice

Food and Chemical Toxicology, Journal Year: 2023, Volume and Issue: 181, P. 114089 - 114089

Published: Oct. 5, 2023

Language: Английский

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Natural compounds as obesity pharmacotherapies

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 38(2), P. 797 - 838

Published: Dec. 11, 2023

Abstract Obesity has become a serious global public health problem, affecting over 988 million people worldwide. Nevertheless, current pharmacotherapies have proven inadequate. Natural compounds garnered significant attention due to their potential antiobesity effects. Over the past three decades, ca. 50 natural been evaluated for preventive and/or therapeutic effects on obesity in animals and humans. However, variations efficacies among these substantial, owing differences experimental designs, including animal models, dosages, treatment durations, administration methods. The feasibility of employing as remained uncertain. In this review, we systematically summarized efficacy mechanisms action each compound models. This comprehensive review furnishes valuable insights development medications based compounds.

Language: Английский

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Polydatin: a potential NAFLD therapeutic drug that regulates mitochondrial autophagy through SIRT3-FOXO3-BNIP3 and PINK1-PRKN mechanisms - a network pharmacology and experimental investigation

Chemico-Biological Interactions, Journal Year: 2024, Volume and Issue: 398, P. 111110 - 111110

Published: June 13, 2024

Language: Английский

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Dietary supplementation with capsaicinoids alleviates obesity in mice fed a high-fat-high-fructose diet

Food & Function, Journal Year: 2024, Volume and Issue: 15(16), P. 8572 - 8585

Published: Jan. 1, 2024

Capsaicinoids are the pungent compounds in chili peppers. The present study investigated effect of capsaicinoids on obesity mice induced by a high-fat-high-fructose diet. Thirty-two male C57BL/6J were randomly divided into four groups (n = 8) and fed one following diets, namely, low-fat diet (LFD), (HFF), an HFF + 0.015% (LCP), 0.045% (HCP), for 12 weeks. Results showed that significantly reversed HFF-induced obesity. Supplementation with improved glucose tolerance, reduced plasma lipids, attenuated inflammation. also hepatic lipid accumulation upregulating expression peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In addition, enhanced production fecal short-chain fatty acids (SCFAs) increased excretion lipids. Gut microbiota analysis revealed decreased Firmicutes/Bacteroidetes ratio beneficially reconstructed microbial community. However, effects intestinal villus length tolerance negligible. conclusion, effectively metabolic syndrome favorably modulating metabolism, improving SCFA production, reshaping gut structure.

Language: Английский

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