针灸和草药(英文)2026,Vol.6Issue(2):220-229,10.DOI:10.1097/HM9.0000000000000186
芒柄花黄素调控肠道菌群减少TMAO生成改善动脉粥样硬化的研究
Formononetin mitigates atherosclerosis by reducing trimethylamine N-oxide production through modulation of gut microbiota in LDLR-/-mice
摘要
Abstract
Objective:Atherosclerosis is the primary cause of cardiovascular disease.Trimethylamine N-oxide(TMAO)is a gut microbiota-derived metabolite that contributes to atherogenesis.Formononetin is an isoflavonoid compound that exhibits potential anti-atherogenic properties,but there are no reports of its role in mitigating atherosclerosis by modulating gut microbiota to reduce TMAO production.In this study,formononetin demonstrated anti-atherosclerotic effects by modulating the gut microbiota to reduce TMAO production. Methods:Eight-week-old male low-density lipoprotein receptor(LDLR)-/-mice were fed on a high-fat diet to induce atherosclerosis.Oil Red O staining was used to assess whether formononetin attenuated atherosclerosis.Fecal transplantation was used to determine whether the anti-atherosclerotic effect of formononetin was mediated by modulation of the gut microbiota.Metagenomic sequencing of the mouse gut microbiota and enzyme-linked immunosorbent assay were used to evaluate whether formononetin reduced TMAO production by modulating gut microbiota. Results:Formononetin significantly reduced the plaque area in the entire aorta and aortic root and increased plaque stability.Fecal transplantation confirmed that the anti-atherosclerotic effect of formononetin was associated with modulation of the gut microbiota.Metagenomic sequencing of the mouse gut microbiota showed that formononetin reduced the relative abundance of Firmicutes,increased the relative abundance of bifidobacteria,and reduced serum TMAO levels.Moreover,formononetin reduced the expression of the cutC gene in the mouse gut microbiota. Conclusions:Formononetin reduced TMAO production by modulating the gut microbiota,thus contributing to its anti-atherosclerotic effects.Modulation of the gut microbiota to reduce TMAO production may represent one of the mechanisms by which formononetin mitigates atherosclerosis.关键词
芒柄花黄素/动脉粥样硬化/三甲胺-N-氧化物/肠道菌群/低密度脂蛋白受体(LDLR)基因敲除小鼠Key words
Atherosclerosis/Formononetin/Gut microbiota/Trimethylamine N-oxide/lipoprotein receptor(LDLR)-/-mice引用本文复制引用
郑国斌,刘上靖,马传瑞,张雯雯,姜涛,陈元利,程雁飞,石佳,季洁,赵琳娜,赵振宇..芒柄花黄素调控肠道菌群减少TMAO生成改善动脉粥样硬化的研究[J].针灸和草药(英文),2026,6(2):220-229,10.基金项目
This work was supported by grants from the Scientific Research Program of Tianjin Education Commission(2024ZD006,2022KJ210),Tianjin Key Medical Discipline Construction Project(TJYXZDXK-3-007B),the National Natural Science Foundation of China(82003747),Tianjin Health Commission and Tianjin Administration of Traditional Chinese Medicine Research topic on the integration of traditional Chinese medicine and Western medicine(2021102),the Extension Project of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine(ZD2020047,ZD202101,2020047). (2024ZD006,2022KJ210)