天然产物调控肠道菌群抗酒精性肝损伤作用机制的研究进展

Research progress on the mechanism of natural products regulating gut microbiota to counteract alcoholic liver injury

摘要

酒精性肝损伤(alcoholic liver injury,ALI)是由长期或过量饮酒引起的肝脏损伤性疾病,全球发病率逐年上升。目前的治疗手段主要依赖人工合成药物,但疗效有限且常出现不良反应。近期研究表明,天然产物可通过调控肠道菌群干预ALI,然而目前尚缺乏系统性综述为其作用机制研究提供参考。本综述提出了一种新型研究策略,阐释天然产物通过靶向肠道菌群-肠肝轴,调控相关代谢途径与细胞损伤机制,从而影响ALI的发生与发展。天然产物因其多途径多靶点及低毒性、不良反应少等优势,近年来在调控肠道菌群、维持微生态平衡方面受到广泛关注。维持肠道菌群平衡可减轻铁死亡、内质网应激及线粒体功能障碍等病理过程,从而缓解肝脏损伤。本文系统综述了天然产物通过调控肠道菌群干预ALI的作用机制研究进展,旨在为中医药防治ALI提供新的研究思路。

Abstract

Alcoholic liver injury (ALI) is a hepatic disease caused by long-term or excessive alcohol consumption, and its global incidence rate has been increasing annually. Current treatments primarily rely on synthetic drugs, which have limited efficacy and often cause adverse reactions. Recent studies indicated that natural products could mitigate ALI via the modulation of gut microbiota, a systematic summary of their mechanisms remains unavailable. In this review, a novel research strategy has proposed, which illustrated that natural products target the gut microbiota-gut-liver axis to modulate related metabolic pathways and cellular injury mechanisms, thereby affecting the pathogenesis and progression of ALI. Natural products have gained widespread attention in recent years for their role in regulating gut microbiota and maintaining microecological balance, owing to their multi-pathway, multi-target effects, low toxicity, and fewer adverse reactions. The maintenance of a balanced gut microbiota could suppress the activation of key pathological processes including ferroptosis, endoplasmic reticulum stress and mitochondrial dysfunction, consequently mitigating hepatic damage. This article seeks to offer new perspectives on the use of traditional Chinese medicine in managing ALI by summarizing recent progress in elucidating how natural products protect against ALI through gut microbiota modulation.

关键词

天然产物 / 肠道菌群 / 酒精性肝损伤 / 铁死亡 / 内质网应激 / 线粒体功能障碍

Key words

natural product / gut microbiota / alcoholic liver injury / ferroptosis / endoplasmic reticulum stress / mitochondrial dysfunction

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基金资助

国家自然科学基金国际(地区)合作与交流项目(82461160264)

国家自然科学基金资助项目(82474056)

上海市卫生健康委卫生学科带头人计划(2022XD037)

上海市白玉兰人才计划浦江项目(23PJD113)

四大慢病重大专项(2023ZD0502605)