Hou XX, Li YW, Song JL, Zhang W, Liu R, Yuan H, Feng TT, Jiang ZY, Li WT, Zhu CL. Cryptotanshinone induces apoptosis of activated hepatic stellate cells via modulating endoplasmic reticulum stress. World J Gastroenterol 2023; 29(17): 2616-2627 [PMID: 37213406 DOI: 10.3748/wjg.v29.i17.2616]
Corresponding Author of This Article
Chuan-Long Zhu, Founder, Professor, Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210009, Jiangsu Province, China. zhuchuanlong@jsph.org.cn
Research Domain of This Article
Pharmacology & Pharmacy
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Xiao-Xue Hou, Jia-Li Song, Wen Zhang, Hui Yuan, Tian-Tong Feng, Zheng-Yi Jiang, Chuan-Long Zhu, Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu Province, China
Yu-Wen Li, Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu Province, China
Rui Liu, Wen-Ting Li, Department of Infectious and Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Haikou 570000, Hainan Province, China
Author contributions: Zhu CL and Hou XX designed the research; Hou XX, Li YW and Song JL performed the research; Li WT analyzed data and wrote the article; Zhang W and Feng TT checked the statistical calculations; Yuan H, Liu R and Jiang ZY commented on and revised the paper; all authors have read and approved the final paper.
Supported byScience and Technology Plan of Hainan Province (Clinical Research Center), No. LCYX202103 and No. LCYX202204; Hainan Province Science and Technology Special Fund, No. ZDYF2022SHFZ067; and Hainan Province Clinical Medical Center.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of The First Affiliated Hospital of Nanjing Medical University (IACUC protocol number: IACUC-2209028).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data generated or analyzed supporting conclusions are included in the current manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chuan-Long Zhu, Founder, Professor, Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210009, Jiangsu Province, China. zhuchuanlong@jsph.org.cn
Received: November 4, 2022 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
ARTICLE HIGHLIGHTS
Research background
Cryptotanshinone (CPT) has been accepted to be an anti-inflammatory molecule.
Research motivation
Hepatic stellate cell (HSC) activation plays an indispensable role in hepatic fibrosis. Inducing apoptosis of activated HSCs can attenuate or reverse fibrogenesis.
Research objectives
This study investigated the effects of CPT treatment on hepatic fibrosis and its underlying mechanism of action.
Research methods
In vitro, we used reverse transcription polymerase chain reaction, Western blot, TUNEL staining and flow cytometry, which demonstrated that CPT can induce HSC apoptosis through the ERS pathway. In vivo, we used liver function kit, enzyme-linked immunosorbent assay, pathological section staining a few columns of technical means to prove that CPT has a certain therapeutic effect on hepatic fibrosis.
Research results
In vitro, CPT was considered to activate HSC apoptosis by promoting endoplasmic reticulum stress (ERS) detrimental response to a certain extent. Main molecules came down to the unfolded protein response signaling pathway. In vivo, We found CPT protected the Carbon tetrachloride (CCL4)-induced hepatic fibrosis. Furthermore, CPT inhibited the levels of the downstream inflammatory cytokines, which were triggered by CCL4-induced hepatic fibrosis.
Research conclusions
CPT can promote apoptosis of HSCs and alleviate hepatic fibrosis through modulating the ERS pathway, which represents a promising strategy for treating hepatic fibrosis.
Research perspectives
Hepatic fibrosis, cirrhosis and liver cancer are typical "trilogy of liver diseases", which seriously endanger human health. Hepatic fibrosis is reversible in the early stage, but it is difficult to reverse in the late stage of liver cirrhosis. Early treatment is therefore essential. CPT is a diterpene quinone compound that is isolated from Salvia miltiorrhiza. CPT has been shown to have anti-oxidant. In this study, we found that CPT could induce apoptosis of activated HSCs and had good prospects for the treatment of hepatic fibrosis.
