Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model

• Published in: Journal of ginseng research Vol. 43; no. 2; pp. 196 - 208
• Main Authors: Choi, Naeun, Kim, Jong Won, Jeong, Hyeneui, Shin, Dong Gue, Seo, Jeong Hun, Kim, Jong Hoon, Lim, Chae Woong, Han, Kang Min, Kim, Bumseok
• Format: Journal Article
• Language: English
• Published: Korea (South) Elsevier B.V 01.04.2019; 고려인삼학회; Elsevier
• Subjects: blood serum; compound K; cytochrome P-450; cytochrome P450 2E1; fatty liver; fermentation; gene expression; ginseng; hepatoma; inflammation; lipids; liver; liver cirrhosis; males; mice; mitogen-activated protein kinase; nonalcoholic steatohepatitis; Panax; polygalacturonase; Saccharomyces; Western blotting; Western diets; 기타의약학; nonalcoholic steatohepatitis; cytochrome P450 2E1; ginseng; compound K; mice
• ISSN: 1226-8453; 2093-4947
• DOI: 10.1016/j.jgr.2017.10.002

Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.