A Controlled Fermented Samjunghwan Herbal Formula Ameliorates Non-alcoholic Hepatosteatosis in HepG2 Cells and OLETF Rats

Abstract

Hepatosteatosis (HS), a clinical feature of fatty liver with the excessive intracellular accumulation of triglyceride in hepatocytes, is manifested by perturbation of the maintenance of liver lipid homeostasis. Samjunghwan (SJH) is an herbal formula used mostly in Korean traditional medicine that is effective against a number of metabolic diseases, including obesity. Herbal drugs, enriched with numerous bioactive substances, possess health-protective benefits. Meanwhile, fermented herbal products enriched with probiotics are known to improve metabolic processes. Additionally, current lines of evidence indicate that probiotics-derived metabolites, termed as postbiotics, produce the same beneficial effects as their precursors. Herein, the anti-HS effects of 5-weeks naturally fermented SJH (FSJH) was investigated with FSJH-mixed chow diet in vivo using Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats as animal models of HS and controls, respectively. In parallel, the anti-HS effects of postbiotic-metabolites of three bacterial strains [Lactobacillus brevis (LBB), Lactococcus lactis (LCL) and Lactobacillus plantarum (LBP)] isolated from FSJH were also evaluated in vitro using the FFAs-induced HepG2 cells. Feeding OLETF rats with FSJH-diet effectively reduced body, liver, and visceral adipose tissue (VAT) weights, produced marked hypolipidemic effects on serum and hepatic lipid parameters, decreased serum AST and ALT levels, and upregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR gene expressions levels. Additionally, exposure of FFAs-induced HepG2 cells to postbiotic metabolic media (PMM) of bacterial strains also produced marked hypolipidemic effects on intracellular lipid contents and significantly unregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR genes expressions levels. Overall, our results indicate that FSJH enriched with fermented metabolites could be an effective anti-HS formulation.

Beyond the Scavenging of Reactive Oxygen Species (ROS): Direct Effect of Cerium Oxide Nanoparticles in Reducing Fatty Acids Content in an In Vitro Model of Hepatocellular Steatosis

“…Therefore, in order to evaluate the ability of CeO 2 NPs to reduce FA content in human hepatic cells, we next used an in vitro model of hepatocellular steatosis based on the administration of OA and PA (2:1 molar ratio) to HepG2 cells. Induction of steatosis in hepatic cells through incubation with a mixture of OA (C18:1n9) and PA (C16:0) is an in vitro steatotic model widely used that is useful to evaluate antisteatotic effects in hepatic cells since it mimics the liver steatosis of NAFLD in patients [30,31,47,48]. OA, a monounsaturated FA, and PA, a saturated FA, are the most abundant FAs present in liver triglycerides [49] and serum [50].…”

Molecular Mechanism of Microbiota Metabolites in Preterm Birth: Pathological and Therapeutic Insights

“…Microbiota affects the metabolic process directly or indirectly by their generated metabolites, also termed as ‘post-biotic metabolites’ (PBM), which produce similar or much better effects compared to their own live parents [ 22 , 68 ]. In general, bacterial metabolites may impact human cell function, inflammation, and disease susceptibility.…”

Probiotics, including nisin‐based probiotics, improve clinical and microbial outcomes relevant to oral and systemic diseases

“…CFU, colony-forming units on nonalcoholic fatty liver disease treatment. 94 96 Also, in mice infected with Salmonella enterica, a gram-negative bacteria, treatment with a combination of nisin and antibiotics significantly decreased the number of Salmonellae in the liver and intestine compared with treatment by antibiotics alone. 97 Furthermore, given the association between periodontal pathogens and liver diseases, 93,98 treatment with a probiotic, like L. lactis and its bacteriocin, nisin, may be beneficial in the treatment of both periodontal and liver diseases.…”

“…Jena et al revealed that Lactococcus protects the liver from inflammation in mice with a western diet‐induced dysbiosis. In addition, a fermented herbal formula, containing L. lactis, effectively improved lipid accumulation and serum markers for liver function . Also, in mice infected with Salmonella enterica, a gram‐negative bacteria, treatment with a combination of nisin and antibiotics significantly decreased the number of Salmonellae in the liver and intestine compared with treatment by antibiotics alone .…”