Abstract

Ginsenoside is a major active component of ginseng, which exhibits various pharmacological properties such as hepatoprotection, tumor suppression and diabetes resistance. In this study, the anti-diabetic effects of protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins were explored and compared in high-fat diet/streptozocin-induced type 2 diabetes mellitus (T2DM) mice. Our results showed that low or high dose (50 mg/kg bodyweight or 150 mg/kg bodyweight) PPD and PPT significantly reduced fasting blood glucose, improved glucose tolerance and insulin resistance in T2DM mice. PPD and PPT also regulated serum lipid-related markers such as reduced total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol in T2DM mice. In addition, PPD and PPT dramatically ameliorated the inflammatory responses by suppressing the secretion of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-6 in serum level and gene expression in liver level, and improved the antioxidant capacity by increasing the superoxide dismutase and decreasing malondialdehyde levels in the serum of T2DM mice. Moreover, the anti-diabetic effect of PPD and PPT appeared to be partially mediated by the suppression of hepatic metabolism genes expression such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase, as well as facilitating lipid metabolism genes expression such as microsomal TG transfer protein in the liver tissues of T2DM mice. Taken together, our results indicated that PPD and PPT might potentially act as natural anti-diabetic compounds to be used for preventing and treating the T2DM and its complications in the future.

Highlights

  • Type 2 diabetes mellitus is a chronic metabolic disease that can impose serious damage on human health and the quality of life (Whiting et al, 2011; Ji et al, 2015)

  • We found that the extent of cellular repair was greater with 150 mg/kg bodyweight protopanaxadiol-type saponins (HPPD) treatment as compared with 150 mg/kg bodyweight protopanaxatriol-type saponins (HPPT) treatment

  • Gene expression levels of PGC1α, phosphoenolpyruvate carboxykinase (PEPCK), and G6Pase were down regulated (p < 0.001) in the liver of mice in the HPPD and HPPT groups as compared to those in the diabetic control (DC) group (Figure 8A). These results indicated that treatment with HPPD and HPPT showed a beneficial effect on abnormal hepatic glucose metabolism

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Summary

Introduction

Type 2 diabetes mellitus is a chronic metabolic disease that can impose serious damage on human health and the quality of life (Whiting et al, 2011; Ji et al, 2015). The majority of oral hypoglycemic drugs used for the treatment of diabetes have demonstrated side effects and adverse reactions (Li et al, 2016). Medicinal herbs were applied to treat wide range of diseases including diabetic mellitus for a long time before the birth of Western Medicine (Basch et al, 2003), and it was well known that their therapeutic function usually accompanied with less side effects compared with the chemical agents such as phenformin and tolbutamide, indicating the use of traditional herbal medicine, which provoked the interest of many researchers worldwide (Yuan et al, 2012)

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