Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

查看全文 作　　者：Yan [1]Wang;Qian [2]Tong;Shu-Rong [1]Ma;Zhen-Xiong [1]Zhao;Li-Bin [1]Pan;Lin [1]Cong;Pei [1]Han;Ran [1]Peng;Hang [1]Yu;Yuan [1]Lin;Tian-Le [1]Gao;Jia-Wen [1]Shou;Xiao-Yang [1]Li;Xian-Feng [2]Zhang;Zheng-Wei [1]Zhang;Jie [1]Fu;Bao-Ying [1]Wen;Jin-Bo [1]Yu;Xuetao [3]Cao;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 100050,China;[2]The First Hospital of Jilin University,Changchun 130021,China;[3]Department of Immunology&Centre for Immunotherapy,Institute of Basic Medical Sciences,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China

出　　处：《Signal Transduction and Targeted Therapy》索引2021年第6卷第3期,共20页

基　　金：supported by CAMS Innovation Fund for Medical Sciences(CIFMS;No.2016-I2M-3-011);the National Natural Science Foundation of China(Nos.81573493 and 81973290);Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(Z141102004414062);the Key Project of Beijing Natural Science Foundation(No.7181007);National Mega-project for Innovative Drugs and the National Megaproject for Innovative Drugs(No.2018ZX09711001-002-002). 摘　　要：The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain.Iin this process,tyrosine hydroxylase(TH)isthe rate-limiting enzyme that hydroxylates tyrosine and generates levodopa(L-dopa)with tetranydrobiopterin(BH_(4))as a coenzyme.Here,we show that oral berberine(BBR)might supply H^(·) through dihydroberberine(reduced BBR produced by bacterial nitroreductase)and promote the production of BHl from dihydrobiopterin;the increased BH,enhances TH activity,which accelerates the production of L-dopa by the gut bacteria.Oral BBR acts in a way similar to vitamins.The L-dopa produced by theintestinal bacteria enters the brain through the circulation and is transformed to dopamine.To verify the gut-brain dialog activatedby BBR's effect,Enterococcus foecalis or Enterococcus faecium was transplanted into Parkinson's disease(PD)mice.The bacteriasignificantly increased brain dopamine and ameliorated PD manifestation in mice;additionally,combination of BBR with bacteriashowed better therapeutic effect than that with bacteria alone.Moreover,2,4,6-trimethy-pyranylium tetrafluoroborate(TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry(MALDI-MS)imaging of dopamine identihed elevated striataldopamine levels in mouse brains with oral Enterococcus,and BBR strengthened the imaging intensity of brain dopamine.Theseresults demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut.Furthermore,a study of 28 patients with hyperlipidemia conhrmed that oral BBR increased bloodfecal L-dopa by the intestinalbacteria.Hence,BBR might improve the brain function by upregulating the biosynthesis of-dopa in the gut microbiota through avitamin-like effect. 关键词：DOPAMINE BERBERINE VITAMIN

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Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

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