二烯丙基二硫醚通过调节肠道微生物群和Nrf2信号通路减轻dss诱导的小鼠结肠纤维化。

IF 5.3 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-10-02 DOI:10.1007/s10787-025-01984-8

Shuangshuang Hai, Yan Chen, Meiyan Zhang, Weixin Liu, Xiaohong Sun

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引用次数: 0

摘要

背景：使用天然药物作为纤维化疾病的辅助治疗最近引起了极大的关注。二烯丙基二硫醚（DADS）是一种来自大蒜的生物活性硫化合物，具有抗氧化、抗炎和免疫调节作用，但其对结肠炎相关肠道纤维化的影响尚不清楚。方法：我们给右旋糖酐硫酸钠（DSS）诱导的慢性结肠炎相关肠道纤维化小鼠口服DADS (80 mg/kg)，并评估临床参数、组织病理学、免疫组织化学、基于16S rdna的肠道微生物群分析和孟德尔随机化分析。结果：DADS治疗改善了体重减轻、疾病活动指数（DAI）、结肠缩短和组织学损伤，减少了炎症浸润和胶原沉积。在机制上，DADS激活Nrf2抗氧化途径，抑制TGF-β1/Smad3纤维化信号，并有利于改变肠道微生物的多样性和组成。结论：DADS通过参与Nrf2，抑制TGF-β1/Smad3和调节肠道微生物群，减轻结肠炎相关的肠道纤维化，凸显其作为新型抗纤维化佐剂的潜力。

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Diallyl disulfide attenuates DSS-induced colonic fibrosis in mice by modulating gut microbiota and Nrf2 signaling.

Background: The use of natural medicines as adjuvant therapies for fibrotic diseases has recently garnered significant attention. Diallyl disulfide (DADS), a bioactive sulfur compound from garlic, exhibits antioxidant, anti-inflammatory, and immunomodulatory effects, but its impact on colitis-associated intestinal fibrosis is unknown.

Methods: We administered DADS (80 mg/kg orally) to mice with dextran sulfate sodium (DSS)-induced chronic colitis-associated intestinal fibrosis and assessed clinical parameters, histopathological, immunohistochemistry, 16S rDNA-based gut microbiota profiling, and Mendelian randomization analysis.

Results: DADS treatment ameliorated weight loss, disease activity index (DAI), colon shortening and histological damage, and reduced inflammatory infiltration and collagen deposition. Mechanistically, DADS activated the Nrf2 antioxidant pathway, inhibited TGF-β1/Smad3 fibrogenic signaling, and favorably altered gut microbial diversity and composition.

Conclusion: By engaging Nrf2, suppressing TGF-β1/Smad3 and modulating the gut microbiota, DADS attenuates colitis-associated intestinal fibrosis, highlight its potential as novel anti-fibrotic adjuvant.

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]