Oral administration of Jinan Red Ginseng and licorice extract mixtures ameliorates nonalcoholic steatohepatitis by modulating lipogenesis

Abstract

Background Nonalcoholic steatohepatitis (NASH) is one of the main chronic liver diseases. NASH is identified by lipid accumulation, inflammation, and fibrosis. Jinan Red Ginseng (JRG) and licorice have been widely used because of their anti-inflammatory and hepatoprotective effects. Hence, this study assessed JRG and licorice extract mixtures' effects on NASH progression. Methods Palmitic acid (PA) and the western diet (WD) plus, high glucose-fructose water were used to induce in vitro and in vivo NASH. Mice were orally administered with JRG-single (JRG-S) and JRG-mixtures (JRG-M; JRG-S + licorice) at 0, 50, 100, 200 or 400 mg/kg/day once a day during the last half-period of diet feeding. Results JRG-S and JRG-M reduced NASH-related pathologies in WD-fed mice. JRG-S and JRG-M consistently decreased the mRNA level of genes related with inflammation, fibrosis, and lipid metabolism. The treatment of JRG-S and JRG-M also diminished the SREBP-1c protein levels and the p-AMPK/AMPK ratio. The FAS protein levels were decreased by JRG-M treatment both in vivo and in vitro but not JRG-S. Conclusion JRG-M effectively reduced lipogenesis by modulating AMPK downstream signaling. Our findings suggest that this mixture can be used as a prophylactic or therapeutic alternative for the remedy of NASH.

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

“… 103 Previous reports have shown that hyperactivation of SREBP-1c promotes hepatic TG accumulation, 104 , 105 suggesting that targeting SREBP-1c for regulating hepatic lipid metabolism might be an appropriate strategy for NASH treatment. 105 , 106 Oltipraz (OPZ) is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of LXR-α, thereby suppressing SREBP-1c activity. 107 Administration of the thiol-reactive agent OPZ significantly attenuated the progression of histologic abnormalities, especially hepatic fibrosis in rats on a CDAA diet.…”

Pharmacological potential of ginseng and ginsenosides in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

“…Jinan red ginseng (JRG), another type of KRG produced at Jinan, Jeollabuk-do, was reported to play a pharmacological role in NASH by modulating lipogenesis in mice and hepatocytes. JRG reduced the palmitic acid (PA)-induced lipotoxicity, inflammation, and oxidative stress in hepatocytes and macrophages [ 43 ]. JRG also decreased the expression of NASH-associated genes in hepatocytes and macrophages [ 43 ].…”

Ginsenoside Rk3 Regulates Nonalcoholic Steatohepatitis by Modulation of Intestinal Flora and the PI3K/AKT Signaling Pathway in C57BL/6 Mice

“…21 Another study showed that a combination of Jinan red ginseng and sweetgum was effective in reducing NASH adipogenesis by modulating AMPK downstream signaling pathways. 22 It is proven that ginsenoside Rk3 improves liver function by lowering serum inflammatory factor levels, reducing inflammatory stress, and recovering the anti-oxidant balance of liver tissue. 20 Never-theless, the preventive effect of ginsenoside Rk3 against NASH…”

“…Panax ginseng saponins are the major active ingredients of ginseng and are involved in the regulation of antioxidant, anti-inflammatory, and anti-tumor pathological processes. , Ginsenoside Rk3 is among the rarely found saponins in the triol group of saponins and has been reported to have physiological effects including antidiabetic, anticancer, and anti-alcoholic fatty liver. − Ginsenosides have been reported to inhibit inflammatory infiltration of the liver parenchyma and improve the progression of NAFLD . Another study showed that a combination of Jinan red ginseng and sweetgum was effective in reducing NASH adipogenesis by modulating AMPK downstream signaling pathways . It is proven that ginsenoside Rk3 improves liver function by lowering serum inflammatory factor levels, reducing inflammatory stress, and recovering the anti-oxidant balance of liver tissue .…”