Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy
Endoplasmic reticulum stress (ERS), mutual crosstalk between autophagy and apoptosis-related signaling pathway, plays an important role in the process of acute liver injury (ALI). The present study was to investigate the effects and underlying mechanisms of Asiatic acid from Potentilla chinensis (AA...
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doaj-83874f98502d4626ba523cfa296cef9d2021-05-20T07:42:33ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-09-01129110375Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagyXiaohong Pang0Qian Qiao1Sayyaphone Vonglorkham2Zhongwen Feng3Lijun Pang4Siyun Chen5Dandan Wang6Lingling Lao7Xing Lin8Jinbin Wei9Pharmaceutical College Guangxi Medical University, Nanning 530021, ChinaPharmaceutical College Guangxi Medical University, Nanning 530021, ChinaPharmaceutical College Guangxi Medical University, Nanning 530021, ChinaPharmaceutical College Guangxi Medical University, Nanning 530021, ChinaPharmaceutical College Guangxi Medical University, Nanning 530021, ChinaPharmaceutical College Guangxi Medical University, Nanning 530021, ChinaPharmaceutical College Guangxi Medical University, Nanning 530021, ChinaPharmaceutical College Guangxi Medical University, Nanning 530021, ChinaCorresponding authors at: Guangxi Medical University, Nanning, Guangxi 530021, China.; Pharmaceutical College Guangxi Medical University, Nanning 530021, ChinaCorresponding authors at: Guangxi Medical University, Nanning, Guangxi 530021, China.; Pharmaceutical College Guangxi Medical University, Nanning 530021, ChinaEndoplasmic reticulum stress (ERS), mutual crosstalk between autophagy and apoptosis-related signaling pathway, plays an important role in the process of acute liver injury (ALI). The present study was to investigate the effects and underlying mechanisms of Asiatic acid from Potentilla chinensis (AAPC) on ALI. The model of ALI in mice was induced by administration with Lipopolysaccharide/D-Galactosamine (LPS/D-GalN). The effects of AAPC on hepatic pathology and hepatocyte apoptosis were observed by hematoxylin-eosin (H&E) staining and TUNEL staining. Serum transaminases activities were measured using an automated biochemical analyzer. Moreover, ERS and autophagy were induced in LO2 cells, respectively. Cell cycle and apoptosis were analyzed using flow cytometry. In addition, ERS and autophagy-related pathways were detected in vivo and in vitro. The results showed that AAPC significantly ameliorated LPS/D-GalN-induced ALI in mice, as evidenced by the improvement of liver pathology and the decrease in serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities. Moreover, AAPC pre-treatment markedly inhibited thapsigargin-induced cell apoptosis, accompanied by cell cycle arrest at S/G1 phase in LO2 cells. AAPC notably inhibited the activation of the PERK/ATF6 and IRE1 pathway, alleviating the extent of ERS. Additionally, AAPC significantly promoted autophagy, as evidenced by the increase in the formation of autophagic vacuoles and the number of autophagosomes as well as the increased expressions of LC3II/I, Beclin-1, Atg5 and Atg7. In summary, our results indicate that AAPC significantly ameliorates ALI by inhibiting the ERS pathway and promoting hepatocyte autophagy.http://www.sciencedirect.com/science/article/pii/S0753332220305680Asiatic acidPotentilla chinensisEndoplasmic reticulum stressHepatocyte autophagy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaohong Pang Qian Qiao Sayyaphone Vonglorkham Zhongwen Feng Lijun Pang Siyun Chen Dandan Wang Lingling Lao Xing Lin Jinbin Wei |
spellingShingle |
Xiaohong Pang Qian Qiao Sayyaphone Vonglorkham Zhongwen Feng Lijun Pang Siyun Chen Dandan Wang Lingling Lao Xing Lin Jinbin Wei Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy Biomedicine & Pharmacotherapy Asiatic acid Potentilla chinensis Endoplasmic reticulum stress Hepatocyte autophagy |
author_facet |
Xiaohong Pang Qian Qiao Sayyaphone Vonglorkham Zhongwen Feng Lijun Pang Siyun Chen Dandan Wang Lingling Lao Xing Lin Jinbin Wei |
author_sort |
Xiaohong Pang |
title |
Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy |
title_short |
Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy |
title_full |
Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy |
title_fullStr |
Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy |
title_full_unstemmed |
Asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy |
title_sort |
asiatic acid ameliorates acute hepatic injury by reducing endoplasmic reticulum stress and triggering hepatocyte autophagy |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-09-01 |
description |
Endoplasmic reticulum stress (ERS), mutual crosstalk between autophagy and apoptosis-related signaling pathway, plays an important role in the process of acute liver injury (ALI). The present study was to investigate the effects and underlying mechanisms of Asiatic acid from Potentilla chinensis (AAPC) on ALI. The model of ALI in mice was induced by administration with Lipopolysaccharide/D-Galactosamine (LPS/D-GalN). The effects of AAPC on hepatic pathology and hepatocyte apoptosis were observed by hematoxylin-eosin (H&E) staining and TUNEL staining. Serum transaminases activities were measured using an automated biochemical analyzer. Moreover, ERS and autophagy were induced in LO2 cells, respectively. Cell cycle and apoptosis were analyzed using flow cytometry. In addition, ERS and autophagy-related pathways were detected in vivo and in vitro. The results showed that AAPC significantly ameliorated LPS/D-GalN-induced ALI in mice, as evidenced by the improvement of liver pathology and the decrease in serum alanine aminotransferase (ALT) and aspartate transaminase (AST) activities. Moreover, AAPC pre-treatment markedly inhibited thapsigargin-induced cell apoptosis, accompanied by cell cycle arrest at S/G1 phase in LO2 cells. AAPC notably inhibited the activation of the PERK/ATF6 and IRE1 pathway, alleviating the extent of ERS. Additionally, AAPC significantly promoted autophagy, as evidenced by the increase in the formation of autophagic vacuoles and the number of autophagosomes as well as the increased expressions of LC3II/I, Beclin-1, Atg5 and Atg7. In summary, our results indicate that AAPC significantly ameliorates ALI by inhibiting the ERS pathway and promoting hepatocyte autophagy. |
topic |
Asiatic acid Potentilla chinensis Endoplasmic reticulum stress Hepatocyte autophagy |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220305680 |
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