Xiaokeyinshui extract combination, a berberine-containing agent, exerts anti-diabetic and renal protective effects on rats in multi-target mechanisms

Ethnopharmacological relevance: Xiaokeyinshui (XKYS) formula, an anti-diabetic formula, was recorded in many ancient Chinese medical books. Xiaokeyinshui extract combination (XEC) originated from this ancient formula, consisting extracts of four herbal drugs, namely, Coptidis Rhizoma, Liriopes Radix, bitter melon, and Cassiae Semen. Objective: Therapeutic effects of Xiaokeyinshui extract combination (XEC) were assessed on diabetic rats. Materials and methods: Herb extracts were prepared and mixed, yielding XEC. XEC were intragastrically given at doses of 260, 380 and 500 mg/kg/d to diabetic rats for 60 days. Anti-diabetic effects of XEC were studied, with measurement of body weight, and assessment of both glycemic control and lipid management. Measurement of oxidative stress and inflammatory cytokines were conducted in accordance to protocols of commercial kits. Parameters related to renal functions were also measured. Western blot (WB) analysis was performed to explore the anti-diabetic and renal protective mechanisms of XEC. Results: Compared to diabetic control, XEC exhibited significant effects in both glucose-lowering and lipid management (p < 0.01). Both oxidative stress and inflammatory cytokines were reduced after treatment of XEC for two months. In addition, XEC exhibited renal protective effects. WB analysis of liver tissue demonstrated that XEC achieved anti-diabetic effects through up-regulation of InsR alpha/IRS-1/PI3K/Akt/GLUT4 signaling pathway and phosphorylation of AMPK. In addition, renal protective effects were also achieved with down-regulation of RAGE and VEGF expressions in kidney. Conclusions: XEC exerts promising anti-diabetic and renal protective effects on diabetic rats in multi-target mechanisms. XEC could be a satisfying alternative treating T2DM and preventing diabetic nephropathy.