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Ginseng Reduces Insulin Resistance

Research out of China determines mechanism by which the medicinal herb may help improve glycemic control through activation of PPAR-γ pathway…. 

Currently diabetes mellitus affects almost 92 million people in China. Traditional Chinese medicine has used herbs medicinally for thousands of years and continues to do so today. Ginseng has been attributed to anti-diabetic properties and is commonly used by this culture in the prevention and treatment of the type 2 diabetes.

Previous yet separate studies have found ginseng to significantly reduce insulin resistance and improve glucose control in both diabetic mice and obese mice. Panax ginseng berry extract in both 200mg and 400mg doses has been previously studied in humans leading to reductions in blood glucose. Steroid glycosides, known as ginsenosides, from Panax ginseng are believed to contribute to the anti-diabetic effects of the herb. What remains uncertain is the underlying mechanism by which ginseng reduces insulin resistance. From their research effort, Gao Y et al. now propose ginsenoside Re reduces insulin resistance through activation of PPAR-γ pathway and inhibition of TNF-α production.

Researchers cultured murine 3T3-L1 adipocytes in order to determine the potential mechanism of action of the ginsenoside Re at the molecular level. The effect of ginsenoside was examined by measuring the concentrations level of triglycerides in the 3T3-L1 cells. By measuring 3H-2-deoxy-d-glucose levels, researchers were able to determine the amount of glucose uptake by the 3T3-L1 cells when stimulated by insulin in the presence of ginsenoside Re compared to control cells. Real time RT-PCR was used to analyze the effect of ginsenoside Re on the expression of genes for PPAR-γ, ap2, adiponectin, IRS-1 (Insulin receptor substrate-1), GLUT4 and TNF-α compared to the PPAR-γ agonist, troglitazone and control cells.

When the researchers treated the 3T3-L1 cells with different concentrations of ginsenoside Re for 8 days, they found a substantial increase in triglyceride concentrations. Following doses of 10 μM, 30 μM and 100 μM of ginsenoside RE, triglyceride levels increased 23%, 29% and 22% respectively compared to the control group. Following the 8 day treatment with ginsenoside Re, increased glucose uptake was reported. When 3T3-L1 cells were stimulated by insulin in the presence of 10 μM and 30 μM ginsenoside Re, the authors recorded an increase by 25% and 29% 3H-2-deoxy-d-glucose uptake respectively.

After 5 days of treatment with ginsenoside Re, real time RT-PCR results showed a significant increase in the expression of PPAR-γ2 mRNA. Compared to control, 30 μM ginsenoside Re increased PPAR-γ2 expression by 4.6 fold whereas 3 μM of troglitazone only increased PPAR-γ2 expression by 1.8 fold. Treatment with ginsenoside Re at a concentration of 60 μM increased the expression of ap2, IRS-1 and adiponectin mRNA by 5.5, 2.6 and 2.2 fold, respectively. In regards to the GLUT4 proteins, Gao and colleagues reported, "Ginsenoside Re did not significantly increase the levels of GLUT4 gene expression which was apparently different from that of troglitazone. Probably ginsenoside Re induces the translocation of GLUT4 to the membranes or increases the synthesis of GLUT4 protein but not increases the gene expression."

Additionally, the authors found the expression and release of TNF-α from 3T3-L1 cells was reduced in the presence of ginsenoside Re compared to both control cells and troglitazone treated cells. Goa et al expand the significance of this reduction by explaining that ginsenoside Re’s inhibition of an inflammatory production of TNF-α leads to improved insulin signaling.

Further evidence is still needed to confirm the anti-diabetic effects ginsenosides found within Ginseng herbal extracts. However, Gao and colleagues concluded, "Ginsenoside Re activated PPAR-γ nuclear receptor through directly increasing expressions of PPAR-γ2 and its targeting genes." The other results found by these researchers support the beneficial effects of ginsenosides giving validity to the use of ginseng in traditional Chinese medicine for the prevention and treatment of diabetes.

Yang Gao, Min-fei Yang, Ya-ping Su,et al., "Ginsenoside Re reduces insulin resistance through activation of PPAR-γ pathway and inhibition of TNF-α production" Journal of Ethnopharmacology, Volume 147, Issue 2, 20 May 2013, Pages 509–516 http://dx.doi.org/10.1016/j.jep.2013.03.057