Published online May 7, 2023. doi: 10.3748/wjg.v29.i17.2616
Peer-review started: November 4, 2022
First decision: February 18, 2023
Revised: February 28, 2023
Accepted: April 10, 2023
Article in press: April 10, 2023
Published online: May 7, 2023
Processing time: 183 Days and 19.2 Hours
Cryptotanshinone (CPT) has wide biological functions, including anti-oxidative, antifibrosis, and anti-inflammatory properties. However, the effect of CPT on hepatic fibrosis is unknown.
To investigate the effects of CPT treatment on hepatic fibrosis and its underlying mechanism of action.
Hepatic stellate cells (HSCs) and normal hepatocytes were treated with different concentrations of CPT and salubrinal. The CCK-8 assay was used to determine cell viability. Flow cytometry was used to measure apoptosis and cell cycle arrest. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot analyses were used to measure mRNA levels and protein expression of endo
We found that CPT treatment significantly reduced fibrogenesis by modulating the synthesis and degradation of the extracellular matrix in vitro. CPT inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in cultured HSCs. Furthermore, we found that CPT promoted apoptosis of activated HSCs by upregulating expression of ERS markers (CHOP and GRP78) and activating ERS pathway molecules (PERK, IRE1α, and ATF4), which were inhibited by salubrinal. Inhibition of ERS by salubrinal partially eliminated the therapeutic effect of CPT in our CCL4-induced hepatic fibrosis mouse model.
CPT can promote apoptosis of HSCs and alleviate hepatic fibrosis through modulating the ERS pathway, which represents a promising strategy for treating hepatic fibrosis.
Core Tip: Hepatic fibrosis is a necessary stage of liver cirrhosis, and there is currently no effective treatment. Cryptotanshinone (CPT), one of the extracts of Chinese herbal medicine Radix Salviae Miltiorrhizae, has a good anti-fibrosis effect. Through this study, we found that CPT can treat hepatic fibrosis by activating endoplasmic reticulum stress and leading to apoptosis of hepatic stellate cells, which provides a new method for the treatment of hepatic fibrosis.