Shenyan Kangfu tablet alleviates diabetic kidney disease through attenuating inflammation and modulating the gut microbiota.

Abstract

Inflammation plays a predominant role in the pathogenesis of diabetic kidney disease (DKD). The Shenyan Kangfu tablet (SYKFT) is a prescription of traditional Chinese medicine for treating chronic kidney disease. However, the concrete mechanism is still unclear. According to previous clinical trial, we explored the effects and potential mechanism on DKD in db/db model supplemented with SYKFT. As a result, SYKFT reduced stimulated blood glucose and HbA1c levels, alleviated renal dysfunction, glomerular and tubular damage, and renal inflammation (TNF-α and IL-1β) in db/db mice. The primary mechanistic study illustrated that SYKFT improved renal injury mainly associated with inhibition of NF-κB in vivo and in vitro. This study further observed that SYKFT increased relative abundance of Firmicutes and decreased Bacteroidetes, showing direct correlation between representative microbiota relative abundance and renal function parameters. SYKFT effectively decreased the relative abundance of Bacteroides, and positive correlation between the relative abundance and protein expression of NF-κB, TNF-α and IL-1β predicted that anti-inflammatory activity of SYKFT was associated with modulating the gut microbiota. Therefore, we first demonstrated SYKFT alleviated DKD through regulating renal inflammatory signaling cascades and intestinal microbiota and also pointed out the role of specific gut microbiota in the development of DKD.