ArticleJournal of advanced research2025
Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Circulating Short-Chain Fatty Acid (SCFA) profiles as a biomarker of gut-brain axis dysfunction: A meta-analysis for the SCFA signature in major depression.Biomedical journal · 2026Pooled it
- Depression remodels tumor microenvironment to drive tumor progression: Bio-behavioural signalling pathways and clinical interventions.Journal of advanced research · 2026Review
- Biphasic oxygen-regulating cyanobacterial hydrogel for synergistic ischemic stroke gas therapy and post-stroke depression prevention.Materials today. Bio · 2026Article
- Gut microbiota-mediated neuroinflammation following stroke: mechanisms and intervention strategies.Journal of translational medicine · 2026Review
- Oral Bioinspired Peroxisome-Engineered Probiotics for Modulating Gut Microbiota Homeostasis and Alleviating Cardiac Chemotherapy Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Harnessing the gut-immune-joint axis: Oral microalgae-based thermoresponsive microspheres enhance intra-articular therapy for rheumatoid arthritis.Bioactive materials · 2026Article
- Inulin Mitigates Reproductive Toxicity from Early Life GenX Exposure in Mice by Inhibiting LPS-TLR4-Mediated Necroptosis: Exploring the Gut-Testis Axis.Environment & health (Washington, D.C.) · 2026Article
- Research progress of blood-brain barrier penetrating and brain diseases therapy by natural biopolymer - based nanomedicine delivery systems.Materials today. Bio · 2026Review
- Gut Microbiota Dysbiosis in Depression: Pathological Correlations, Molecular Pathways, and Therapeutic Interventions.International journal of molecular sciences · 2026Review
- Central Neurobiological Mechanisms of Acupuncture in Post-Stroke Depression: Multi-Target and Network-Based Regulation.Neuropsychiatric disease and treatment · 2026Review
- Integrated bioinformatics and experimental validation identifies SOX2 as a key therapeutic target for chronic atrophic gastritis/gastric cancer-depression comorbidity.Frontiers in oncology · 2026Article
- Electroacupuncture Alleviates Oxidative Stress and Cuproptosis in Metabolic Dysfunction-Associated Steatotic Liver Disease Mice Through Activation of the NRF2/ARE Pathway.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Modified Jie-Yu-He-Huan Capsule in Post-Stroke Depression Treatment: Insights from DIA Proteomic and PRM Validation.Drug design, development and therapy · 2026Article
- Article
- Akkermansia muciniphila: a microbial guardian against oxidative stress-gut microbiota crosstalk and clinical prospects.Journal of translational medicine · 2025Review
- The Influence of Sirtuin 6 on Chondrocyte Senescence in Osteoarthritis Under Aging: Focusing on Mitochondrial Dysfunction and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- An orally-administered nanotherapeutics with gold nanospheres supplying for rheumatoid arthritis therapy by re-shaping gut microbial tryptophan metabolism.Journal of nanobiotechnology · 2025Article
- The role of the microbiome on immune homeostasis of the host nervous system.Frontiers in immunology · 2025Review
- From Microbial Homeostasis to Systemic Pathogenesis: A Narrative Review on Gut Flora's Role in Neuropsychiatric, Metabolic, and Cancer Disorders.Journal of inflammation research · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSirt6-mediated gut microbiota plays a vital role in poststroke depression (PSD). Icariside Ⅱ (ICS Ⅱ) is a naturally-occurring neuroprotectant with Sirt6 induction potency. However, it is unknown whether ICS Ⅱ protects against PSD through modulation of gut microbiota.
objectiveThis study aimed to reveal the effect and potential mechanisms of ICS Ⅱ on PSD, and the role of the microbiota-gut-brain axis was investigated.
methodsUsing middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) to establish post-stroke depression (PSD) mice, we assessed anti-depressant effects of ICS Ⅱ via behavioral tests, immunohistochemistry, and western blot. Transcriptome profiling, molecular docking, and surface plasmon resonance were used to identify key targets. 16S rDNA genomic-derived taxonomic profiling and fecal microbiota transplantation (FMT) were conducted to figure out the mechanistic role of the gut microbiota and short-chain fatty acids (SCFAs).
resultsICS Ⅱ ameliorated depressive-like behaviors in PSD mice as evidenced by sucrose preference test, forced swimming test and tail suspension test. ICS Ⅱ restored mitochondrial function, reduced oxidative damage and pro-inflammatory cytokines both in brain and intestine through regulation of Sirt6/NF-κB pathway. ICS Ⅱ significantly increased the abundance of gut microbiota (such asAkkermansia and Ligilactobacillus), enhanced SCFAs concentrations, repaired intestinal barrier integrity and upreglated the tight junction protein expression. FMT from ICS II-treated mice replicated these benefits, confirming gut microbiota's role. Mechanistically, ICS Ⅱ directly bound to Sirt6 and enhanced its activity. However, ICS Ⅱ-mediated neuroprotection was neutralized in PSD mice or hydrogen peroxide-induced enteric glial cells when Sirt6 was absent.
conclusionOur findings expand the pharmacological properties of ICS II by demonstrating its ability to ameliorate PSD through modulation of the microbiota-gut-brain axis. ICS Ⅱ, as a novel Sirt6 activator, could be translated into an alternative microbiota-targeted avenue for coping with PSD.
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