A bioinformatic and mechanistic study elicits the antifibrotic effect of ursolic acid through the attenuation of oxidative stress with the involvement of ERK, PI3K/Akt, and p38 MAPK signaling pathways in human hepatic stellate cells and rat liver

Drug Design, Development and Therapy
Wenhua HeXuan Zhu

Abstract

NADPH oxidases (NOXs) are a predominant mediator of redox homeostasis in hepatic stellate cells (HSCs), and oxidative stress plays an important role in the pathogenesis of liver fibrosis. Ursolic acid (UA) is a pentacyclic triterpenoid with various pharmacological activities, but the molecular targets and underlying mechanisms for its antifibrotic effect in the liver remain elusive. This study aimed to computationally predict the molecular interactome and mechanistically investigate the antifibrotic effect of UA on oxidative stress, with a focus on NOX4 activity and cross-linked signaling pathways in human HSCs and rat liver. Drug-drug interaction via chemical-protein interactome tool, a server that can predict drug-drug interaction via chemical-protein interactome, was used to predict the molecular targets of UA, and Database for Annotation, Visualization, and Integrated Discovery was employed to analyze the signaling pathways of the predicted targets of UA. The bioinformatic data showed that there were 611 molecular proteins possibly interacting with UA and that there were over 49 functional clusters responding to UA. The subsequential benchmarking data showed that UA significantly reduced the accumulation of type I collagen ...Continue Reading

Citations

Jun 11, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Shigeru Kawakami, Mitsuru Hashida
Nov 19, 2019·Frontiers in Pharmacology·Si-Zhe WanXuan Zhu
Oct 1, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Guangyao LiYuanjia Hu
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tommaso StefaniMaría Del Rayo Camacho-Corona
Mar 2, 2021·Expert Opinion on Therapeutic Patents·Xuanyi LiKejiang Lin

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Methods Mentioned

BETA
flow cytometry
electrophoresis
MDA
GTPase
nucleotide exchange

Software Mentioned

VEGA ZZ
AutoDock
- CPI
DAVID
Gene ID Conversion Tool
DDI
Image Lab
BioCarta

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