The Gut Microbiota‐Xanthurenic Acid‐Aromatic Hydrocarbon Receptor Axis Mediates the Anticolitic Effects of Trilobatin

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract Current treatments for ulcerative colitis (UC) remain limited, highlighting the need novel therapeutic strategies. Trilobatin (TLB), a naturally derived food additive, exhibits potential anti‐inflammatory properties. In this study, dextran sulfate sodium (DSS)‐induced animal model is used to investigate effects of TLB on UC. It found significantly alleviates DSS‐induced UC in mice, as evidenced by reduction disease activity index, an increase colon length, improvement histopathological lesions. Furthermore, treatment results decrease proinflammatory cytokines and cytokines. mitigates modulating intestinal microbiota, particularly Akkermansia , which enhances tryptophan metabolism upregulates production xanthurenic acid (XANA). To confirm role TLB‐induced microbiota changes, experiments are performed with pseudogerm‐free mice fecal transplantation. also identified XANA key metabolite that mediates TLB's protective effects. Both markedly activate aromatic hydrocarbon receptor (AhR). Administration AhR antagonist abrogates their effects, thereby confirming involvement underlying mechanism. conclusion, study reveals mechanism through correcting imbalances, regulating metabolism, enhancing production, activating AhR.

Язык: Английский

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Sirtuins: Promising Therapeutic Targets to Treat Ischemic Stroke

Biomolecules, Год журнала: 2023, Номер 13(8), С. 1210 - 1210

Опубликована: Авг. 1, 2023

Stroke is a major cause of mortality and disability globally, with ischemic stroke (IS) accounting for over 80% all cases. The pathological process IS involves numerous signal molecules, among which are the highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes known as sirtuins (SIRTs). SIRTs modulate various biological processes, including cell differentiation, energy metabolism, DNA repair, inflammation, oxidative stress. Importantly, several studies have reported correlation between IS. This review introduces general aspects SIRTs, their distribution, subcellular location, enzyme activity, substrate. We also discuss regulatory roles potential mechanisms in Finally, we describe current therapeutic methods based on such pharmacotherapy, non-pharmacological therapeutic/rehabilitative interventions, epigenetic regulators, stem cell-derived exosome therapy. data collected this study will potentially contribute to both clinical fundamental research geared towards developing effective candidates future treatment

Язык: Английский

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Trilobatin, a Naturally Occurring GPR158 Ligand, Alleviates Depressive-like Behavior by Promoting Mitophagy

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер 73(9), С. 5163 - 5179

Опубликована: Фев. 18, 2025

The G-protein-coupled receptor (GPR158), an orphan receptor, is highly expressed in the medial prefrontal cortex (mPFC) and identified as a novel therapeutic target for depression. Trilobatin naturally occurring food additive with potent neuroprotective properties. However, its pharmacological effects molecular mechanisms against depression remain unknown. Therefore, we explored whether trilobatin alleviates by targeting GPR158. Our results indicated that alleviated chronic unpredictable mild stress (CUMS)-induced depressive-like behavior mice. Mitophagy contributed to antidepressant-like effect of trilobatin, evidenced qRT-PCR array. Furthermore, up-regulated autophagy-associated protein expression, restored mitochondrial dynamic balance, inhibited oxidative mPFC mice after CUMS insult corticosterone-induced primary neuron injury. Intriguingly, directly bound GPR158 decreased level expression. deficiency attenuated through promoting mitophagy, while antidepressant was strengthened GPR158-deficient findings highlight GPR158-mediated mitophagy acts crucial reveal new-found property trilobatin: serving ligand safeguard from mitophagy.

Язык: Английский

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Electroacupuncture ameliorates cognitive impairment and white matter injury in vascular dementia rats via activating HIF-1α/VEGF/VEGFR2 pathway

Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Role of sirtuins in cerebral ischemia-reperfusion injury: Mechanisms and therapeutic potential

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 310, С. 143591 - 143591

Опубликована: Апрель 27, 2025

The high incidence and mortality rate of cardiac arrest (CA) establishes it as a critical clinical challenge in emergency medicine globally. Despite continuous advances advanced life support (ALS) technology, the prognosis for patients experiencing remains poor, with cerebral ischemia reperfusion injury (CIRI) being significant determinant adverse neurological outcomes increased mortality. Sirtuins (SIRTs) are class highly evolutionarily conserved NAD+-dependent histone deacylenzymes capable regulating expression various cytoprotective genes to play neuroprotective role CIRI. SIRTs mainly regulate levels downstream proteins such PGC 1-α, Nrf 2, NLRP 3, FoxOs, PINK 1 inhibit inflammatory response, attenuate oxidative stress, improve mitochondrial dysfunction, promote angiogenesis, apoptosis while reducing Natural active ingredients widely used protein level body because their multi-components, multi-pathway, multi-target, minimal toxic side effects. However, these naturally still face many challenges related drug targeting, pharmacokinetic properties, delivery. emergence vigorous development new delivery systems, nanoparticles, micromilk, exosomes, provide strong solving above problems. In context rapid molecular biology non-coding RNA (NcRNA), represented by miRNA LncRNA, offers great potential achieving gene-level precision medicine. multidisciplinary integration, combining biotechnology, omics technologies, artificial intelligence, material science will strongly deepening basic research expand application. This review describes major signaling pathways targeting mitigate CIRI, well current status Chinese Western medical means intervention SIRTs. Meanwhile, possible solutions application targeted drugs summarized. industrial crossover, direction future is discussed valuable reference researchers clinicians diagnosis treatment effects

Язык: Английский

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Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 28, 2025

Ischemic stroke (IS) remains a leading cause of mortality and disability worldwide, driven by genetic predispositions environmental interactions, with epigenetics playing pivotal role in mediating these processes. Specific modifying enzymes that regulate epigenetic changes have emerged as promising targets for IS treatment. DNA methyltransferases (DNMTs), ten-eleven translocation (TET) dioxygenases, histone acetyltransferases (HATs), deacetylases (HDACs) are central to regulation. These maintain dynamic balance between methylation/demethylation acetylation/deacetylation, which critically influences gene expression neuronal survival IS. This review is based on both vivo vitro experimental studies, exploring the roles DNMT/TET HAT/HDAC IS, evaluating their potential therapeutic targets, discussing use natural compounds modulators develop novel treatment strategies.

Язык: Английский

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Role of histone deacetylases and sirtuins in the ischaemic stroke: a systematic review and meta-analysis of animal studies

Stroke and Vascular Neurology, Год журнала: 2025, Номер unknown, С. svn - 004159

Опубликована: Май 7, 2025

Background Treatment of ischaemic stroke requires exploration novel neuroprotective strategies owing to the constraints thrombolytic therapy. Recent research implies that modulation histone deacetylases (HDAC) or sirtuins (SIRT) could be beneficial in achieving this goal. Methods This systematic review and meta-analysis evaluates effectiveness HDAC/SIRT enzyme treating acute stroke. It includes relevant studies but excludes human vitro non-primary studies. An electronic search was conducted across databases PubMed, Web Science Scopus until 20 March 2025. The methodological quality assessed using a modified SYRCLE risk bias tool. Infarct volume neurological responses were extracted as key outcomes, random-effects infarct for directly targeting enzymes. Results A 71 involving over 1600 animals focused on treatments, predominantly male rodents transient middle cerebral artery occlusion model. Most treatments administered intraperitoneally, starting from inception ischaemia 5 days afterwards. Non-selective HDAC inhibitors SIRT1 modulators targeted most frequently. with 95% CI showed an overall effect estimate −1.529 suggested non-selective exhibit promise reducing size. Additionally, agonists SIRT3/7, SIRT6, HDAC1, along SIRT5, HDAC6 HDAC3, may play significant role treatment Importantly, have been found effective when within 24 hours following ischaemia. Discussion study highlights promising trials by focusing outcome. However, relying exclusively not fully capture these treatments.

Язык: Английский

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Angiogenesis as a Therapeutic Target of (Poly)phenols: Tackling Cancer and Vascular‐Related Complications

Molecular Nutrition & Food Research, Год журнала: 2025, Номер unknown

Опубликована: Май 15, 2025

ABSTRACT Targeting angiogenesis as a strategy for treating cancer or vascular‐associated complications is an inspiring field many investigators. An active area within this discipline the search agents capable of modulating in order to ameliorate its structural and functional abnormalities associated with these diseases. (Poly)phenols are broad group molecules, which fall category natural compounds therapeutic potential. These potential medicinal effects have launched considerable number studies investigating pro‐ and(or) anti‐angiogenic properties (poly)phenols different (patho)physiological settings. The purpose review summarize current evidence role angiogenesis. This will guide reader through preclinical human investigations describing pathophysiological context, cellular molecular mechanisms associated, key points design evaluation described, suggest new approaches be considered future overcome limitations.

Язык: Английский

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Astragaloside IV promotes angiogenesis by targeting SIRT7/VEGFA signaling pathway to improve brain injury after cerebral infarction in rats

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 168, С. 115598 - 115598

Опубликована: Окт. 9, 2023

Cerebral infarction (CI) has become one of the leading causes death and acquired disability worldwide. Astragaloside IV (AST IV), basic components Astragalus membranaceus, a protective effect on CI. However, underlying mechanism not been conclusively elucidated. Therefore, this study aims to explore AST improving brain injury after Middle cerebral artery occlusion (MCAO) oxygen-glucose deprivation/reoxygenation (OGD/R) were used simulate in SD rats HUVECs cells. Neurologic score, Evans blue, TTC HE staining observe rats. Cell viability migration measured vitro. Angiogenesis was detected by immunofluorescence tube formation assay, cell cycle flow cytometry. Western blot find expression related proteins. Molecular docking, virtual mutation, site-directed mutagenesis, MST, lentivirus silencing for target validation. The results showed that alleviated neurological impairment promoted angiogenesis Moreover, greatly increased transcription levels SIRT6 SIRT7, but had no SIRT1-SIRT5, viability, migration, S phase ratio OGD/R-induced HUVECs. Furthermore, up-regulated protein expressions CDK4, cyclin D1, VEGFA VEGF2R. Interestingly, only bound also SIRT7. Silencing SIRT7 neutralizes positive effects IV. Taken together, present revealed may improve tissue damage CI targeting SIRT7/VEGFA signaling pathway promote angiogenesis.

Язык: Английский

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Aberrant expression and regulatory role of histone deacetylase 9 in vascular endothelial cell injury in intracranial aneurysm

Biomolecules and Biomedicine, Год журнала: 2023, Номер unknown

Опубликована: Авг. 12, 2023

Intracranial aneurysm (IA) is one of the most challenging cerebrovascular lesions for clinicians. The aim this study was to investigate abnormal expression and role histone deacetylase 9 (HDAC9) in IA-associated injury vascular endothelial cells (VECs). First, IA tissue normal arterial were collected VECs isolated from patients. levels HDAC9, microRNA (miR)-34a-5p, growth factor-A (VEGFA) determined. Cell viability, proliferation, apoptosis, migration assessed by Counting Kit-8 (CCK-8) assay, EdU staining, TUNEL transwell assay. binding miR-34a-5p VEGFA analyzed dual-luciferase accumulation HDAC9 lysine acetylation at H3 (H3K9, H3K14, H3K18) on promoter detected chromatin immunoprecipitation results showed that increased decreased tissues cells. Silencing inhibited apoptosis VECs, whereas overexpression exerted opposite functions. accumulated decrease reducing locus-specific further promoted expression. Knockdown or reversed protective silencing injury. In conclusion, our suggests may be a therapeutic target IA.

Язык: Английский

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