Effects of Qijian mixture on type 2 diabetes assessed by metabonomics, gut microbiota and network pharmacology

Qjjian mixture, a new traditional Chinese medicine (TCM) formula comprising of Astragalus membranaceus, Romulus euonymi, Coptis chinensis and Pueraria lobata, was designed to ameliorate the type 2 diabetes (T2D), and its safety and efficacy were evaluated in the research by metabonomics, gut micro biota and system pharmacology. To study the hypoglycemic effect of Qijian mixture, male KKay mice (28-30g, 8-9 week) and C57/BL6 mice (18-19 g, 8-9 week) were used. Thirty KKay diabetic mice were randomly distributed into 5 groups, abbreviated as Model group (Model), Low Qijian Mixture group (QJM(L)), High Qijian Mixture group (QJM(H)), Chinese Medicine (Gegen Qinlian Decoction) Positive group (GGQL), and Western Medicine (Metformin hydrochloride) Positive group (Metformin). C57/BL6 was considered as the healthy control group (Control). Moreover, a system pharmacology approach was utilized to assess the physiological targets involved in the action of Qijian mixture. There was no adverse drug reaction of Qijian mixture in the acute toxicity study and HE result, and, compared with Model group, Qijian mixture could modulate blood glycemic level safely and effectively. Callan Mixture was lesser effective than metformin hydrochloride; however, both showed similar hypoglycemic trend. Based on H-1 NMR based metabonomics study, the profoundly altered metabolites in Qijian mixture treatment group were identified. Qjjian mixture-related 55 proteins and 4 signaling pathways, including galactose metabolism, valine, leucine and isoleucine degradation metabolism, aminoacyl-tRNA biosynthesis metabolism and alanine, aspartate and glutamate metabolism pathways, were explored. The PCoA analysis of gut micro biota revealed that Qijian mixture treatment profoundly enriched bacteroidetes. In addition, the system pharmacology paradigm revealed that Qijian mixture acted through TP53, AKT1 and PPARA proteins. It was concluded that Qjjian mixture effectively alleviated T2D, and this effect was linked with the altered features of the metabolite profiles and the gut microbiota. (C) 2018 Elsevier Ltd. All rights reserved.