Ginsenoside Rg3 Attenuates Early Hepatic Injury via Inhibiting PPARγ- and Ang II-Related Inflammation and Fibrosis in Type II Diabetic Mice

Abstract

Ginsenoside Rg3 (Rg3), a natural product abundantly present in Korean Red Ginseng, is widely known for its anti-tumor activity. In our previous studies, we had further demonstrated that Rg3 has protective effects on the hearts, kidneys, and aortas of animals with hypertension or hypercholesterolemia, and its main mechanisms include down-regulation of angiotensin II (Ang II) levels and activation of peroxisome proliferator-activated receptor gamma (PPARγ) pathway in those tissues. In this study, the protective effects of Rg3 on liver were determined in db/db mice, a most recognized type II diabetes (T2DM) animal model with nonalcoholic fatty liver disease (NAFLD). The results showed that Rg3 did not have obvious effects to the body weight, blood glucose, and lipids of db/db mice. According to the results of histology examination, Rg3 could not improve steatosis in the hepatic tissue, too. But Rg3 did attenuate alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation in serum and collagen deposition in hepatic tissue. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) showed that Rg3 upregulated PPARγ and downregulated Ang II in hepatic tissue in db/db mice, which resulted in reducing activities of transforming growth factor β (TGF-β)/connective tissue growth factor (CTGF) pathway, downregulating the levels of inflammatory cytokines and attenuating collagen accumulation. In conclusion, although it has no obvious effect on steatosis in the hepatic tissue, Rg3 indeed attenuates early hepatic injury from NAFLD via inhibiting PPARγ- and Ang II-related inflammation and fibrosis in T2DM db/db mice. These effects are independent of reducing blood glucose and lipids, and the mechanisms are similar to the protective effects of Rg3 in hypertension and hypercholesterolemia animals in our previous studies.