AUTHOR=Lyu Yuanfeng , Lin Lin , Xie Yuning , Li Dan , Xiao Min , Zhang Yufeng , Cheung Stanley Chun Kai , Shaw Pang Chui , Yang Xiao , Chan Paul Kay Sheung , Kong Alice Pik Shan , Zuo Zhong 

TITLE=Blood-Glucose-Lowering Effect of Coptidis Rhizoma Extracts From Different Origins via Gut Microbiota Modulation in db/db Mice

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.684358

DOI=10.3389/fphar.2021.684358

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold><italic>Coptidis rhizoma</italic> extracts (CREs) have been used widely for their anti-diabetic and anti-microbial activities, and berberine/jatrorrhizine/coptisine/palmatine are the primary bioactive components. Although guidelines have adopted content analyses of these components as a quality control method for CREs, it is difficult to differentiate the CREs from different sources using this method because of the lack of indications for their related pharmacological activities.</p><p><bold>Purpose:</bold> To explore the effect of CREs (CREA/CREB/CREC) with different compositions of major components on the gut microbiota and blood glucose levels in d<italic>b/db</italic> mice.</p><p><bold>Methods:</bold> Degradation of berberine/jatrorrhizine/coptisine/palmatine from CREA/CREB/CREC in rat/mouse intestinal contents and their impact on nine common gastrointestinal bacteria were investigated. In addition, the effects of oral administration of CREA/CREB/CREC for 2 weeks on the gut microbiota and blood glucose levels in d<italic>b/db</italic> mice were monitored <italic>via</italic> insulin/glucose tolerance test (ITT/GTT), insulin concentration, homeostatic model assessment of insulin resistance and fecal 16S rRNA sequencing.</p><p><bold>Results and Conclusion:</bold> The total amount of berberine/jatrorrhizine/coptisine/palmatine was highest in CREA. <italic>Clostridium perfringens</italic> was strongly inhibited by all three CREs, with CREA demonstrating the most significant inhibitory effects on minimum inhibitory concentration, time-kill kinetics, and ATP production. In d<italic>b/db</italic> mice, CREA resulted in the most significant decrease in ITT/GTT and depicted different changes in the microbiota from CREB/CREC. Thus, CREs with different compositions of berberine/jatrorrhizine/coptisine/palmatine differed in terms of time-kill kinetics and ATP production assays on <italic>C. perfringens</italic>. CREA revealed the potent bacterial inhibitory effects and glucose-lowering activity.</p>