Abstract
Type 2 diabetes is a metabolic disorder caused by abnormal carbohydrate metabolism, and closely associated with abnormal lipid metabolism and hepato-renal dysfunction. This study investigated the anti-diabetic and hepato-renal protective properties of ziyuglycoside I (ZG01) derivative on type 2 diabetes. ZG01 was isolated from roots of Sanguisorba officinalis and chemically modified by deglycosylation and esterification to obtained ziyuglycoside II methyl ester (ZG02-ME). Here, we showed that ZG02-ME has stronger anti-diabetic activity than the original compound (ZG01) through decreasing blood glucose, glycated hemoglobin (HbA1c), and insulin levels in a mouse model of type 2 diabetes (db/db mice). We further found that ZG02-ME treatment effectively ameliorated serum insulin, leptin and C-peptide levels, which are key metabolic hormones, in db/db mice. In addition, we showed that elevated basal blood lipid levels were decreased by ZG02-ME treatment in db/db mice. Furthermore, treatment of ZG02-ME significantly decreased serum AST, ALT, BUN, creatinine, and liver lipid peroxidation in db/db mice. These results demonstrated that compared to ZG01, chemically modified ZG02-ME possess improved anti-diabetic properties, and has hepato-renal protective activities in type 2 diabetes.
Highlights
Diabetes mellitus is a group of metabolic disorders caused by an abnormal carbohydrate metabolism and mainly linked to abnormal blood glucose and insulin levels or an ineffective response of cells to insulin [1]
We carried out a functional activity assay to evaluate the anti-diabetic activity of ziyuglycosides on type 2 diabetes using db/db mice
We further observed that the glycated hemoglobin (HbA1c) concentration was higher in db/db mice, which was significantly reduced by treatment with ZG01 and ZG02-ME with reduction rates of 19.4% and 37.3%, respectively
Summary
Diabetes mellitus is a group of metabolic disorders caused by an abnormal carbohydrate metabolism and mainly linked to abnormal blood glucose and insulin levels or an ineffective response of cells to insulin [1]. In clinical therapy for type 2 diabetes, hypoglycemic agents such as metformin, α-glycosidase inhibitors, thiazolidines, and sulfornylurea derivatives are available for use. These compounds have side effects including weight-gain and cardiovascular problems, and providing them at a relatively low cost is still a challenge to the medical system [4]. Ziyuglycosides are a group of primary terpenoid constituents in S. officinalis that has been shown to exhibit a wide ranges of biological actions, including hemostasis [22]. No previous studies have evaluated anti-diabetic activity of ziyuglycosides in an in vivo setting, especially on the non-insulin-dependent diabetes (Type 2 diabetes). The present study was performed to investigate the role of ziyuglycosides in regulating blood glucose, plasma insulin, and serum lipid parameter levels in db/db mice, a mouse model of diabetes type 2, along with the renal and liver function parameters
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