Blood-Glucose-Lowering Effect of Coptidis Rhizoma Extracts From Different Origins via Gut Microbiota Modulation in db/db Mice
Yuanfeng Lyu, Lin Lin, Yuning Xie, Dan Li, Min Xiao, Yufeng Zhang, Stanley C.K. Cheung, Pang Chui Shaw, Xiao Yang, Paul K.S. Chan, Alice P.S. Kong, Zhong Zuo
Abstract
Background: Coptidis rhizoma 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. Purpose: 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 b/db mice. Methods: 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 b/db mice were monitored via insulin/glucose tolerance test (ITT/GTT), insulin concentration, homeostatic model assessment of insulin resistance and fecal 16S rRNA sequencing. Results and Conclusion: The total amount of berberine/jatrorrhizine/coptisine/palmatine was highest in CREA. Clostridium perfringens 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 b/db 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 C. perfringens . CREA revealed the potent bacterial inhibitory effects and glucose-lowering activity.