Veratrilla baillonii Franch Could Alleviate Lipid Accumulationin LO2 Cells by Regulating Oxidative, Inflammatory, and Lipid Metabolic Signaling Pathways.

Xian-Ju Huang,Shuai Liang,Cai-Jing He,Guang-Zhong Yang,Jing Wang,Zhang Zhao,Jun Li

doi:10.3389/fphar.2020.575772

Abstract

Based on the pathological theory of lipid metabolism and using network pharmacology, this study was designed to investigate the protective effect of water extract of Veratrilla baillonii (WVBF) on non-alcoholic fatty liver disease (NAFLD) model using LO2 cells and to identify the potential mechanism underlying the effect. The components of V. baillonii were identified from the public database of traditional Chinese medicine systems pharmacology database (TCMSP). Cytoscape software was used to construct the related composite target network. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out for critical nodes. The BioGPS database was used to determine the distribution of the target in tissues and organs. Moreover, the inhibitory effect of V. baillonii was further investigated using an in vitro hepatocyte NAFLD model. Fourteen active components were then selected from the 27 known compounds of V. baillonii. The targets of gene enrichment analysis were mainly distributed in the lipid catabolism-related signaling pathway. Network analysis revealed that five target genes of TNF, MAPK8, mTOR, NF-ĸB, and SREBP-1c were key nodes and played important roles in this process. Organ localization analysis indicated that one of the core target site of V. baillonii was liver tissue. The results of the in vitro study revealed that WVBF can alleviate the inflammatory response and lipid accumulation in LO2 hepatocytes by inhibiting oxidative stress and the adipocytokine signaling pathway. Genes and proteins related to the lipid synthesis, such as SREBP-1C, acetyl-CoA carboxylase (ACC), and fatty acid synthase (FASN), were significantly decreased, and PPARα expression is significantly increased with WVBF administration. In conclusion, V. baillonii may regulate local lipid metabolism and attenuate oxidative stress and inflammatory factors through the PPARα/SREBP-1c signaling pathway. The present study also indicates that multiple components of V. baillonii regulate multiple targets and pathways in NAFLD. The findings highlight the potential of V. baillonii as a promising treatment strategy for nonalcoholic fatty liver injury.

Highlights

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is a metabolic syndrome characterized by hepatocellular steatosis and fat storage without a history of excessive alcohol consumption (Younossi et al, 2016)
Compound Profiling and Disease Target Identification The following databases were searched to identify the compounds in V. baillonii: traditional Chinese medicine systems pharmacology database (TCMSP), a unique pharmacology platform that captures the relationships between herbal ingredients, targets, and diseases: SymMap
In order to identify the potential targets of V. baillonii, the molecular similarity match tool was used based on the simplified molecular input line entry specification (SMILES) in the similarity ensemble approach (SEA) (P

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is a metabolic syndrome characterized by hepatocellular steatosis and fat storage without a history of excessive alcohol consumption (Younossi et al, 2016). NAFLD accounts for 25.2% of global burden of disease epidemics, with approximately 30% of adults having underlying lipid metabolic disorders (Zobair et al, 2016). NAFLD affects nearly one-third of the world’s population and the prevalence of this disorder is increasing every year (Hu et al, 2019). Based on the underlying pathological conditions, NAFLD can further develop into simple fatty liver, non-alcoholic steatohepatitis (NASH), fatty liver fibrosis, or cirrhosis, which significantly increases the associated mortality (Perumpail et al, 2017; Ipsen et al, 2018). Since no pharmacological therapy has been approved for the treatment of NAFLD so far, there is an urgent necessity to define multiple components, multiple targets and pathways of traditional Chinese medicine (TCM) based strategies of future interventions

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