Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Chrysophanol administration alleviates bleomycin-induced pulmonary fibrosis by inhibiting lung fibroblast proliferation and Wnt/β-catenin signaling

Xiangwei Qi¹, Yamei Ou², Ying Xie², Kangrong Cai³, Hualin Gan⁴, Qiqi Wan⁴, Hao Xie⁴, Zeqing Song²

¹Second Clinical Medical Skills Training Center, GuangDong Medical University, Dongguan City, Guangdong Province 523808; ²Department of Respiratory Medicine, Shenzhen Longhua District Central Hospital, Shenzhen City, Guangdong Province 518000; ³Analytical Center, GuangDong Medical University, Dongguan City, Guangdong Province 523808; ⁴Department of Respiratory Medicine, The Fourth People’s Hospital of Nanhai, Foshan City, Guangdong Province 528211, China.

For correspondence:- Zeqing Song Email: ZeqingSongghj@163.com Tel:+8675521014681

Accepted: 27 April 2020 Published: 31 May 2020

Citation: Qi X, Ou Y, Xie Y, Cai K, Gan H, Wan Q, et al. Chrysophanol administration alleviates bleomycin-induced pulmonary fibrosis by inhibiting lung fibroblast proliferation and Wnt/β-catenin signaling. Trop J Pharm Res 2020; 19(5):971-976 doi: 10.4314/tjpr.v19i5.9

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To determine the functional effect of chrysophanol (CH) on bleomycin (BLM)-induced pulmonary fibrosis (PF) and reveal its mechanism of action.

Methods: A mouse model of PF was established by intratracheal instillation of BLM (5 mg/kg), prior to CH administration. Masson’s trichrome staining was used to analyze interstitial fibrosis and collagen deposition. Hydroxyproline (HYP) content was measured, and lung fibroblast viability determined by MTT assay. Bronchoalveolar lavage fluid (BALF) was collected, and levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and interferon-γ (IFN-γ) were evaluated using enzyme-linked immunosorbent assays (ELISA). expression of cell signaling, adhesion, and apoptotic proteins were determined by western blotting.

Results: Administration of CH reduced collagen deposition and HYP content, downregulated α-smooth muscle actin, upregulated E-cadherin, and decreased the levels of TNF-α, IL-1β, IL-6, and IFN-γ in BLM-treated mice. The viability of lung fibroblasts was also reduced, and Bcl-2-associated X protein and cleaved caspase-3 were upregulated after CH treatment in BLM-treated mice. In addition, CH treatment in BLM-treated mice significantly increased levels of cytoplasmic β-catenin but decreased its expression in the nucleus.

Conclusion: Administration of CH alleviated BLM-induced PF by inhibiting lung fibroblast proliferation and nuclear translocation of β-catenin. Thus, this study provides a potential therapeutic strategy for PF.

Keywords: Chrysophanol, Bleomycin, Pulmonary fibrosis, Hydroxyproline, E-cadherin