Korean red ginseng improves metabolic parameters, mitochondrial DNA copy numbers and inflammatory markers in type 2 diabetes mouse

Abstract

Introduction : Diabetes mellitus is characterized by insulin resistance of target organ and dysfunction of pancreas. Although the underlying whole mechanisms remain unclear, type 2 diabetes mellitus is associated with mitochondrial dysfunction including mitochondrial loss and over-production of oxidants. In addition to the traditional method of strict glucose control, the mechanisms of several traditional herbal medicines which have been known to have glucose lowering effect are based on anti-inflammatory and anti - oxidative action. In Korea, Korean red ginseng is most famous herbal medicines to have anti-diabetic effect. Some studies revealed that ginseng had anti-diabetic efficacy depends on improvement of systemic inflammatory biomarkers but the mechanism of anti-diabetic efficacy is not fully understood. The aim of this study was to investigate the effects of Korean red ginseng supplementation on metabolic parameters including fasting blood glucose concentrations, insulin sensitivity and lipid profiles. We also examined whether regulation of Korean red ginseng is partly mediated through mitochondrial metabolism such as biogenesis and/or decrease of intracellular inflammation levels in an animal model of type 2 diabetes mellitus.Method : C57BL/KsJ db/db mice and C57BL/KsJ db/+ mice were divided into 3 groups: db/+ mice with chow diet (n=8, control group), db/db mice with high-fat diet (n=8, db/db control group), and db/db mice with high-fat diet and Korean red ginseng administration (n=7, db/db ginseng group) for 12 weeks. After 12 weeks, metabolic parameters including fasting blood glucose concentrations, hemoglobin A1C (HbA1c), insulin and lipid profiles were determined using high-performed liquid chromatography. Mitochondrial DNA (mt DNA) was measured using qPCR. The expression of mitochondrial biogenesis markers including PGC-1α and T-fam and the expression of inflammatory markers such as IL-6, COX-2, and CRP were measured in liver tissues using quantitative real time PCR analysis. Result : Mean body weight were not significantly different between db/db control group and db/db/ ginseng group. And after 7 weeks, db/db ginseng group showed significantly lower mean fasting blood glucose level than that of db/db control group. Compared with db/db control group, glucose index (fasting glucose, HbA1c, insulin, HOMA-IR) and LDL cholesterol levels are significantly lowered in db/db ginseng group. And the mitochondrial DNA copy numbers were also significantly higher in db/db ginseng group than those in db/db control group. After Korean red ginseng administration, PGC-1α and TFAM were significantly decreased and TFAM was even more decreased than that of control group. Inflammatory protein precursors IL-6, COX-2, and CRP were significantly increased in db/db control group. Korean red ginseng administration made mRNA expression related to IL-6, COX-2 and CRP significantly decreased even more than the control group, so the inflammatory score was calculated and were significantly increased in db/db control group and significantly decreased in db/db ginseng group.Conclusion : Korean red ginseng improved blood glucose levels and insulin sensitivity and it may be correlated with mitochondrial function and oxidative inflammatory stress. Korean red ginseng could be a useful additive nutraceutical in type 2 diabetes mellitus.