艾叶乙醇提取物通过调节肠道微生物群和肝脏信号通路改善非酒精性脂肪性肝炎诱导的肝纤维化。
Artemisia argyi ethanol extract ameliorates nonalcoholic steatohepatitis-induced liver fibrosis by modulating gut microbiota and hepatic signaling.
作者信息
Erdenebileg Saruul, Kim Myungsuk, Nam Yunseong, Cha Kwang Hyun, Le Tam Thi, Jung Sang Hoon, Nho Chu Won
机构信息
Smart Farm Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute of Natural Products, Gangneung, Gangwon-do, 25451, South Korea; Natural Product Applied Science, KIST School, University of Science and Technology (UST), Gangneung, Gangwon-do, 25451, South Korea.
Natural Product Applied Science, KIST School, University of Science and Technology (UST), Gangneung, Gangwon-do, 25451, South Korea; Natural Product Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute of Natural Products, Gangneung, Gangwon-do, 25451, South Korea; Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do, 26426, South Korea.
出版信息
J Ethnopharmacol. 2024 Oct 28;333:118415. doi: 10.1016/j.jep.2024.118415. Epub 2024 Jun 6.
ETHNOPHARMACOLOGICAL RELEVANCE
Artemisia argyi (AA), a herbal medicine traditionally used in Asian countries, to treat inflammatory conditions such as eczema, dermatitis, arthritis, allergic asthma and colitis. However, the mechanism of action of this plant with regard to hepatitis and other liver-related diseases is still unclear.
AIM
This study aimed to investigate the effects of AA ethanol extract on NASH-related fibrosis and gut microbiota in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model.
METHODS
Male C57BL/6J mice were fed CDAHFD, with or without AA ethanol extract treatment. Biochemical markers, lipid profiles, hepatic mRNA expression levels of key genes, and the fibrosis area were assessed. In vitro, TGF-β-stimulated human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs) were used to elucidate the effects of AA ethanol extract on fibrosis and steatosis. 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways.
RESULTS
Treatment with the AA ethanol extract improved plasma and liver lipid profiles, modulated hepatic mRNA expression levels of antioxidant, lipolytic, and fibrosis-related genes, and significantly reduced CDAHFD-induced hepatic fibrosis. Gut microbiota analysis revealed a marked decrease in Acetivibrio ethanolgignens abundance upon treatment with the AA ethanol extract, and its functional pathways were significantly correlated with NASH/fibrosis markers. The AA ethanol extract and its active components (jaceosidin, eupatilin, and chlorogenic acid) inhibited fibrosis-related markers in LX-2 and mHSC.
CONCLUSION
The AA ethanol extract exerted therapeutic effects on CDAHFD-induced liver disease by modulating NASH/fibrosis-related factors and gut microbiota composition. Notably, AA treatment reduced the abundance of the potentially profibrotic bacterium (A. ethanolgignens). These findings suggest that AA is a promising candidate for treating NASH-induced fibrosis.
民族药理学相关性
艾草（AA）是一种在亚洲国家传统上用于治疗炎症性疾病的草药，如湿疹、皮炎、关节炎、过敏性哮喘和结肠炎。然而，这种植物在肝炎和其他肝脏相关疾病方面的作用机制仍不清楚。
目的
本研究旨在探讨艾草乙醇提取物对胆碱缺乏、L-氨基酸限定、高脂肪饮食（CDAHFD）诱导的小鼠模型中与非酒精性脂肪性肝炎（NASH）相关的纤维化和肠道微生物群的影响。
方法
雄性C57BL/6J小鼠喂食CDAHFD，同时给予或不给予艾草乙醇提取物处理。评估生化标志物、脂质谱、关键基因的肝脏mRNA表达水平以及纤维化面积。在体外，使用转化生长因子-β（TGF-β）刺激的人肝星状LX-2细胞和小鼠原代肝星状细胞（mHSCs）来阐明艾草乙醇提取物对纤维化和脂肪变性的影响。采用16S rRNA测序、QIIME2和PICRUST2分析肠道微生物多样性、组成和功能途径。
结果
艾草乙醇提取物处理改善了血浆和肝脏脂质谱，调节了抗氧化、脂解和纤维化相关基因的肝脏mRNA表达水平，并显著降低了CDAHFD诱导的肝纤维化。肠道微生物群分析显示，用艾草乙醇提取物处理后，乙醇产乙酸杆菌丰度显著降低，其功能途径与NASH/纤维化标志物显著相关。艾草乙醇提取物及其活性成分（紫花前胡苷、灯盏乙素和绿原酸）抑制了LX-2和mHSC中与纤维化相关的标志物。
结论
艾草乙醇提取物通过调节NASH/纤维化相关因子和肠道微生物群组成，对CDAHFD诱导的肝病发挥治疗作用。值得注意的是，艾草处理降低了潜在促纤维化细菌（乙醇产乙酸杆菌）的丰度。这些发现表明，艾草是治疗NASH诱导纤维化的有前途的候选药物。
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