Berberine treats atherosclerosis via a vitamine-like effect downregulating Choline-TMA-TMAO production pathway in gut microbiota

查看全文 作　　者：Shu-Rong [1]Ma;Qian [2]Tong;Yuan [1]Lin;Li-Bin [1]Pan;Jie [1]Fu;Ran [1]Peng;Xian-Feng [2]Zhang;Zhen-Xiong [1]Zhao;Yang [2]Li;Jin-Bo [1]Yu;Lin [1]Cong;Pei [1]Han;Zheng-Wei [1]Zhang;Hang [1]Yu;Yan [1]Wang;Jian-Dong [1]Jiang

机构地区：[1]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences/Peking Union Medical College,Beijing,China;[2]The First Hospital of Jilin University,Changchun,China

出　　处：《Signal Transduction and Targeted Therapy》索引2022年第7卷第8期,共13页

基　　金：funded by the CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2021-1-I2M-007,2016-I2M-3-011);the National Natural Science Foundation of China(Nos.82173888,81973290);Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(Z141102004414062)。 摘　　要：Trimethylamine-N-oxide(TMAO)derived from the gut microbiota is an atherogenic metabolite.This study investigates whether or not berberine(BBR)could reduce TMAO production in the gut microbiota and treat atherosclerosis.Effects of BBR on TMAO production in the gut microbiota,as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacterial,HFD-fed animals and atherosclerotic patients,respectively.We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase(CutC)and flavincontaining monooxygenase(FMO)in the gut microbiota.This action was performed by BBR’s metabolite dihydroberberine(a reductive BBR by nitroreductase in the gut microbiota),via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway.Oral BBR decreased TMAO production in animal intestine,lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters.Moreover,21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2%after oral BBR(0.5 g,bid)for 4 months(^(*)P<0.05,n=21);whereas the plaque score in patients treated with rosuvastatin plus aspirin,or clopidogrel sulfate or ticagrelor(4 months,n=12)increased by 1.9%.TMA and TMAO in patients decreased by 38 and 29%in faeces(^(*)P<0.05;^(*)P<0.05),and 37 and 35%in plasma(^(***)P<0.001;^(*)P<0.05),after 4 months on BBR.BBR might treat atherosclerotic plaque at least partially through decreasing TMAO in a mode of action similar to that of vitamins. 关键词：VITAMIN INTESTINE TMAO

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Berberine treats atherosclerosis via a vitamine-like effect downregulating Choline-TMA-TMAO production pathway in gut microbiota

参考文献(69)

引证文献(52)

耦合文献(78)

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