Synergistic interactions of catalpol and stachyose in STZ-HFD induced diabetic mice: Synergism in regulation of blood glucose, lipids, and hepatic and renal function

Abstract Objective Rehmanniae Radix has been traditionally used to treat diabetes. Catalpol (CAT) and stachyose (STA) are two of the main bioactive compounds in Rehmannia Radix and found to have similar therapeutic effects on diabetes and its complications. In this paper, we aimed to investigate whether there were synergistic therapeutic effects of CAT and STA on diabetes. Methods Streptozotocin (STZ) with the feeding of high-sugar-high-fat diet (HFD) was applied to induce diabetic C57BL/6 mice. STZ-HFD induced diabetic mice were then divided into model and six medical-treated groups: metformin (MET), STA, CAT, and three combinations of CAT:STA (1:1, 1:2, 2:1). Blood, liver, and kidney samples were isolated after six-week oral administration for biochemical assays of serum lipids, the indicators of kidney and liver functions and HE staining for liver tissues. Results It turned out that CAT, STA and their three combinations (1:1, 1:2, 2:1) could effectively control body weight, blood glucose, kidney weight and liver weight index, and well regulate levels of TC, HDL-c, TG, ALT, and TBA. In addition, CAT and its combination with STA at the ratio of 2:1 could significantly improve albumin content, compared to that in model group. STA and CAT and their combinations showed the improvements on kidney function in terms of urinary creatinine (Ucr). However, there were no such consistent observations on serum creatinine (Scr) and creatinine clearance rate (Ccr). The combination of CAT and STA at the ratio of 1:1 exhibited the better adjusting effects on kidney weight and liver weight indexes and the levels of ALT, Ucr, Scr, and Ccr. Our results demonstrated that the combinations of CAT and STA especially 1:1 showed similar or better improvements on diabetes-associated complications, compared to the sole CAT or STA treatment. Conclusion Thus, we concluded that there were synergistic therapeutic effects between CAT and STA on STZ/HFD-induced type 2 diabetes. This project provided insights and technical supports for the innovation of discovering bioactive constituents in Rehmannia Radix and studying its integrative mechanism in curing diabetes.