Livogrit Prevents Methionine-Cystine Deficiency Induced Nonalcoholic Steatohepatitis by Modulation of Steatosis and Oxidative Stress in Human Hepatocyte-Derived Spheroid and in Primary Rat Hepatocytes

Abstract

The prevalence of nonalcoholic steatohepatitis (NASH), characterized by fatty liver, oxidative injury, and inflammation, has considerably increased in the recent years. Due to the complexity of NASH pathogenesis, compounds which can target different mechanisms and stages of NASH development are required. A robust screening model with translational capability is also required to develop therapies targeting NASH. In this study, we used HepG2 spheroids and rat primary hepatocytes to evaluate the potency of Livogrit, a tri-herbal Ayurvedic prescription medicine, as a hepatoprotective agent. NASH was developed in the cells via methionine and cystine-deficient cell culture media. Livogrit at concentration of 30 µg/mL was able to prevent NASH development by decreasing lipid accumulation, ROS production, AST release, NFκB activation and increasing lipolysis, GSH (reduced glutathione), and mitochondrial membrane potential. This study suggests that Livogrit might reduce the lipotoxicity-mediated ROS generation and subsequent production of inflammatory mediators as evident from the increased gene expression of FXR, FGF21, CHOP, CXCL5, and their normalization due to Livogrit treatment. Taken together, Livogrit showed the potential as a multimodal therapeutic formulation capable of attenuating the development of NASH. Our study highlights the potential of Livogrit as a hepatoprotective agent with translational possibilities.

The role of CXCL family members in different diseases

“…According to bioinformatics analysis, CXCL2 is one of the key genes associated with NASH [ 81 ]. CXCL5 expression elevated in NASH cells and can be inhibited via Livogrit to alleviate the progression of NASH [ 82 ]. CXCL10 also takes a crucial part in NASH.…”

MulticomponentAyurvedaformulationLodhrasavamameliorates steatosis and lipotoxicity in HepG2 cell model of NAFLD

“…Livogrit, a tri-herbal Ayurvedic medicine, was studied for its hepatoprotective effect on methionine and cysteine deficient NASH models in both HepG2 spheroids and rat primary hepatocytes. It reduced fat accumulation and ROS production and increased lipolysis hence attenuating NASH (Balkrishna et al, 2022) NAFLD is characterized by the accumulation of lipid droplets (LDs) in the hepatocytes, referred to as hepatic steatosis. It is considered as the "first-hit" in the development of NAFLD.…”

Anti-oxidant Response of Lipidom Modulates Lipid Metabolism inCaenorhabditis elegansand in OxLDL-Induced Human Macrophages by Tuning Inflammatory Mediators

“…In order to decipher the mode of action of Lipidom we evaluated the gene expression of OxLDL induced THP1 macrophages and found that Lipidom acts on the pathways responsible for inflammation (TNFα, MCP-1), lipid accumulation (FAS, ABCG1, FGF-21) and oxidative stress (Nrf2) [24][25][26]. It was found that Lipidom was able to normalize the expression of these genes by a multifaceted mode of action.…”