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整合代谢组学和网络药理学揭示槟榔成瘾的机制。

Integrated metabolomics and network pharmacology to reveal the mechanism of areca nut addiction.

机构信息

School of Environment and Civil Engineering, Jiangnan University, Wuxi, Jiangsu, China.

National Engineering Research Center of Cereal Fermentation and Food Biomanufacturing, Jiangnan University, Wuxi, Jiangsu, China.

出版信息

Addict Biol. 2023 Dec;28(12):e13352. doi: 10.1111/adb.13352.

DOI:10.1111/adb.13352
PMID:38017647
Abstract

As a chewing hobby, areca nut (Areca catechu L.) has become the most common psychoactive substance in the world, besides tobacco, alcohol and caffeinated beverages. Moreover, as a first-class carcinogen designated by International Agency for Research on Cancer, long-term chewing areca nut can result in oral mucosal diseases and even oral cancer. To clarify the potential mechanism of areca nut addiction, an integrated strategy of metabolomics and network pharmacology was adopted in this study. Network pharmacology study indicated that all the key targets related to areca nut addiction could be regulated by arecoline and pointed out the importance of G-protein coupled receptor signalling pathway. Analysis results of mice plasma metabolome and faeces metabolome intervened by arecoline suggested that the component may affect the dopamine system and 5-HT system by regulating phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, primary bile acid biosynthesis, glycerophospholipid metabolism and intestinal flora structure. Moreover, the potential importance of bile acids in formation of addictive behaviour of chewing areca nut was investigated by integrative analysis of the relationships between metabolites and intestinal flora. The study can provide scientific basis for the addiction intervention and treatment of areca nut chewers.

摘要

作为一种咀嚼嗜好,槟榔(Areca catechu L.)已成为继烟草、酒精和含咖啡因饮料之后世界上最常见的精神活性物质。此外,由于被国际癌症研究机构指定为一级致癌物,长期咀嚼槟榔会导致口腔黏膜疾病,甚至口腔癌。为了阐明槟榔成瘾的潜在机制,本研究采用代谢组学和网络药理学的综合策略。网络药理学研究表明,与槟榔成瘾相关的所有关键靶标都可以通过槟榔碱进行调节,并指出 G 蛋白偶联受体信号通路的重要性。槟榔碱干预小鼠血浆代谢组和粪便代谢组的分析结果表明,该成分可能通过调节苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代谢、初级胆汁酸生物合成、甘油磷脂代谢和肠道菌群结构来影响多巴胺系统和 5-HT 系统。此外,通过整合代谢物与肠道菌群之间的关系分析,研究了胆汁酸在咀嚼槟榔成瘾行为形成中的潜在重要性。该研究可为槟榔咀嚼者的成瘾干预和治疗提供科学依据。

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