Anti-hepatosteatosis effect of fermented-Samjunghwan via postbiotic metabolites in HepG2 cells and OLETF rats. Fermented-SJH and Anti-heapotosteatosis effect

Hepatosteatosis (HS), a clinical feature of fatty liver with an excessive intracellular accumulation of triglyceride in hepatocytes. Basically, deregulated signaling of hepatic lipid metabolic process is a major cause of HS. Fermented foods improve the metabolic process which has chock-full of beneficial bacteria and recently these probiotic-derived metabolites (called postbiotic) provided same beneficial effects as their precursors. Herbal medicines which are rich sources of natural bioactive compounds have been very effective in the treatment of various dreadful diseases. Samjunghwan (SJH), an herbal formula used mostly in the Korean traditional medicine that is effective for the treatment of a number of metabolic diseases including obesity. In the present study, an attempt has been made to explore the anti-HS effect of postbiotic-metabolites-media (PMM) of three isolated strains (Lactobacillus brevis (LBB), Lactococcus lactis (LCL) and Lactobacillus plantarum (LBP) from naturally fermented SJH (FSJH) for in vitro study and FSJH mixed chow diet for in vitro study. The experimental models were free fatty acids (FFAs) treated HepG2 cells and Long-Evans Tokushima Ostuka (LETO)/Otuska Long-Evans Tokushima fatty (OLETF) rats treated with PMM and FSJH mixed chow diet respectively. The severity of hepatosteatosis was determined by staining techniques (hematoxylin and eosin, and oil red o) in HepG2 cells and rats liver; lipid profile (total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), aspartate transaminase (AST), and alanine transaminase (ALT)) were determined in HepG2 cell and rats (serum, liver, and fecal). Quantitative expression levels of lipid-metabolic genes (HMGCOR, SREBP, ACC, AMPK and LDLR) were explored in HepG2 cells and rat liver. Our in vitro results indicated that the PMM treatment effectively reduces the hepatic lipid accumulation and significantly reduced the TG, TC, AST, ALT levels and improved the HDL level, while the expression level of HMGCOR, SREBP, and ACC were significantly up-regulated, and AMPK and LDLR were significantly down-regulated compared with FFAs treated HepG2 cells. In the in vivo results, the body, liver, and visceral adipose tissue (VAT) were reduced; the TG, TC, AST, and ALT were decreased in serum and liver while increased in the fecal sample of FSJH group compared with OLETF group. Like in vitro, the similar pattern of expression of HMGCOR, SREBP, and ACC were up-regulated and AMPK and LDLR were down-regulated were observed in FSJH group compared with OLETF group. Overall, our results indicate that FSJH could be effectively used as an anti-HS formulation consist postbiotic-metabolites.