1--Actylbritannilactone Ameliorates Alcohol-Induced Hepatotoxicity Through Regulation of ROS/Akt/NF-κB-Mediated Apoptosis and Inflammation

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Jun 6

PMID 35664604

Authors

Li-Ya Xie

Zhen Yang

Ying Wang

Jun-Nan Hu

Ya-Wei Lu

Hao Zhang

Shuang Jiang

Wei Li

Affiliations

Soon will be listed here.

Abstract

1--Acetylbritannilactone (ABL) is a marker component of L. and is reported to exhibit multiple pharmacological activities, including antiaging, anti-inflammatory, and antidiabetic properties. Although the protective effect of L. on animal models of liver injury has been widely reported, the effect of ABL on alcohol-induced liver damage has not been confirmed. The present study was designed to investigate the protective effect of ABL against alcohol-induced LO2 human normal liver cell injury and to further clarify the underlying mechanism. Our results revealed that ABL at concentrations of 0.5, 1, and 2 μM could remarkably suppress the decreased viability of LO2 cells stimulated by alcohol. In addition, ABL pretreatment improved alcohol-induced oxidative damage by decreasing the level of reactive oxygen species (ROS) and the excessive consumption of glutathione peroxidase (GSH-Px), while increasing the level of catalase (CAT) in LO2 cells. Moreover, Western blotting analysis showed that ABL pretreatment activated protein kinase B (Akt) phosphorylation, increased downstream antiapoptotic protein Bcl-2 expression, and decreased the phosphorylation level of the caspase family including caspase 9 and caspase 3 proteins, thereby attenuating LO2 cell apoptosis. Importantly, we also found that ABL significantly inhibits the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the secretion of proinflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin (IL-1β). In conclusion, the current research clearly suggests that the protective effect of ABL on alcohol-induced hepatotoxicity may be achieved in part through regulation of the ROS/Akt/NF-κB signaling pathway to inhibit inflammation and apoptosis in LO2 cells. (The article path map has not been seen.).

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