Research Paper Volume 13, Issue 5 pp 6592—6605
Lupeol ameliorates LPS/D-GalN induced acute hepatic damage by suppressing inflammation and oxidative stress through TGFβ1-Nrf2 signal pathway
- 1 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China
- 2 The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, Guangdong, China
- 3 Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou 510515, Guangdong, China
- 4 Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong, China
Received: May 26, 2020 Accepted: July 25, 2020 Published: March 11, 2021https://doi.org/10.18632/aging.202409
How to Cite
Copyright: © 2021 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acute hepatic damage is a severe condition characterized by inflammation and oxidative stress, which is a serious threat to people's life and health. But there are few effective treatments for acute liver injury. Therefore, safe and effective therapeutic approaches for preventing acute liver damage are urgently needed. Lupeol is a natural compound, which has significant antioxidant and anti-inflammatory properties in liver disease. However, the protective mechanism of lupeol against acute liver injury remains unclear. Here, zebrafish and mutant mice were utilized to investigate the protective effects of lupeol against lipopolysaccharide (LPS)/ D-galactosamine(D-GalN) -induced liver injury and the underlying mechanisms. We found that pretreatment with lupeol attenuated the LPS/D-GalN-induced liver injury by decreasing the infiltration of inflammatory cells and reducing pro-inflammatory cytokines. We also demonstrated that lupeol could protect injured liver from oxidative stress by downregulating the expression of TGFβ1 and upregulating Nrf2. Notably, our experimental results provided the support that lupeol effectively protected against LPS/D-GalN-induced acute liver injury via suppression of inflammation response and oxidative stress, which were largely dependent on the upregulation of the Nrf2 pathway via downregulating TGFβ1.
ALI: acute liver injury; TGFβ1: transforming growth factor β1; TGFβr1: transforming growth factor β receptor 1; Nrf2: Nuclear factor erythroid 2-related factor 2; LPS: lipopolysaccharide; D-GalN: D-galactosamine; WT: wild-type; EGFP: enhanced green fluorescent protein; hpf: hours post fertilization; dpf: days post fertilization; RIPA: radioimmunoprecipitation; PFA: paraformaldehyde; DMSO: dimethyl sulfoxide; OCT: optimal cutting tissue; H&E: hematoxylin and eosin; IF: immunofluorescence; IHC: immunohistochemistry; RNS: reactive nitrogen species; ROS: reactive oxygen species; GSH: glutathione; ANOVA: analysis of variance.