Ginsenoside Re Improves Inflammation and Fibrosis in Hepatic Tissue by Upregulating PPARγ Expression and Inhibiting Oxidative Stress in db/db Mice

Abstract

Ginsenoside Re (Re) is the main component of “Zhenyuan Capsule” (ZYC), which was wildly used in clinic in China for adjunctive treatment of coronary heart disease (CHD) and type II diabetes (T2DM). Nonalcoholic fatty liver disease (NAFLD) is one of the most important complications of T2DM, as well as an important risk factor of CHD. The aim of the present study was to investigate the effects of Re on NAFLD in db/db mice, one of the most recognized gene deficient animal models on T2DM. Sixteen db/db mice and sixteen wild-type mice were divided into four groups and orally administered Re or placebo in equal volume. According to the results, Re showed no obvious effect on blood glucose, lipids, or body weight of db/db mice. Histology pictures of hepatic tissue showed that Re did not improve steatosis, too. However, some evidence suggested that hepatic injury in db/db mice was attenuated by Re administering. Collagen deposition and aminotransferase elevation were significantly downregulated in the DB + Re group compared to those in the DB Group. The mechanisms of the protect effects of Re represented in db/db mice with NAFLD might be inhibiting oxidative stress and the reupregulation of peroxisome proliferator-activated receptor γ (pparγ) expression. The results of this study indicated that ZYC might be able to help T2DM patients with NAFLD to control the progress of NAFLD as an alternation of thiazolidinediones, synthetic agonists of PPARγ, whose side effects and adverse events should not be ignored.

The Efficacy of Panax ginseng for the Treatment of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

“…Although the underlying mechanisms could not be delineated by this study, included articles have suggested several protective mechanisms mediated by Panax ginseng treatment against NAFLD. First, in hepatocytes, Panax ginseng treatment suppressed NAFLD-induced cellular stress responses, such as oxidative stress [ 23 , 50 ], ER stress [ 35 , 47 ], and mitochondrial dysfunction [ 26 ]. In addition, the administration of Panax ginseng has beneficial effects on hepatic energy metabolism by activating AMP-activated protein kinase [ 22 , 29 , 56 , 58 ] but inhibiting the mammalian target of rapamycin complex 1 [ 37 ], resulting in the normalization of hepatic glucose [ 30 ] and lipid metabolism [ 32 , 33 , 34 , 41 ] in NAFLD.…”

“…( A ) A graph of the risk in the bias of included studies. ( B ) A summary of the risk of bias in the included studies [ 7 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ].…”

“… The effect of Panax ginseng on the levels of liver injury markers in NAFLD-induced animals. Forest plots for comparison: ( A ) Alanine aminotransferase (ALT) levels [ 7 , 19 , 20 , 23 , 24 , 27 , 28 , 29 , 30 , 31 , 32 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 47 , 48 , 49 , 50 , 52 , 54 , 55 , 56 , 58 ]. ( B ) Aspartate aminotransferase (AST) levels [ 19 , 23 , 27 , 28 , 29 , 30 , 31 , 32 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 44 , 45 , 47 , 48 , 49 , 50 ...…”

“… The effect of Panax ginseng on hepatic lipid metabolism in NAFLD-induced animals. Forest plots for comparison: ( A ) Triglyceride (TG) levels [ 7 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 35 , 38 , 39 , 40 , 41 , 44 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 56 , 58 ]. ( B ) Total cholesterol (TC) levels [ 7 , 19 , 20 , 21 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 35 , 38 , 39 , 40 , 41 , 44 , …”

“…( B ) Total cholesterol (TC) levels [ 7 , 19 , 20 , 21 , 23 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 35 , 38 , 39 , 40 , 41 , 44 , 46 , 47 , 49 , 50 , 51 , 52 , 56 , 57 , 58 ]. ( C ) High-density lipoprotein (HDL) levels [ 7 , 19 , 21 , 23 , 27 , 28 , 32 , 35 , 38 , 39 , 44 , 46 , 49 , 50 , 51 , 52 , 56 , 58 ]. ( D ) Low-density lipoprotein (LDL) levels [ 7 , 19 , 21 , 25 , 27 ,…”