Gypenosides Attenuate Pulmonary Fibrosis by Inhibiting the AKT/mTOR/c-Myc Pathway

Suqing Liu; Qingqing Yang; Binbin Dong; Chunhui Qi; Tao Yang; Ming Li; Shan He; Baojun Liu; Jinfeng Wu

doi:10.3389/fphar.2021.806312

Gypenosides Attenuate Pulmonary Fibrosis by Inhibiting the AKT/mTOR/c-Myc Pathway

Front Pharmacol. 2022 Jan 14:12:806312. doi: 10.3389/fphar.2021.806312. eCollection 2021.

Authors

Suqing Liu¹, Qingqing Yang^{1

2}, Binbin Dong³, Chunhui Qi⁴, Tao Yang⁵, Ming Li¹, Shan He¹, Baojun Liu⁶, Jinfeng Wu¹

Affiliations

¹ Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
² Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
³ Department of Pediatrics, Huashan Hospital North, Fudan University, Shanghai, China.
⁴ Department of Respiratory Medicine, Qingpu District Traditional Chinese Medicine Hospital, Institute of Integrative Medicine, Fudan University, Shanghai, China.
⁵ Department of Cardiovascular Disease, Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁶ Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Abstract

Gypenosides (Gyps), the major active constituents isolated from Gynostemma pentaphyllum, possess anti-inflammatory and antioxidant activities. Previous studies have demonstrated that Gyps displayed potent ameliorative effects on liver fibrosis and renal fibrosis. In this study, we found that Gyps significantly reduced the mortality of bleomycin-induced pulmonary fibrosis mice (40% mortality rate of mice in the model group versus 0% in the treatment group). Masson staining showed that Gyps could reduce the content of collagen in the lung tissue of pulmonary fibrosis mice Masson staining and immunohistochemistry demonstrated that the expression of the collagen gene α-SMA and fibrosis gene Col1 markedly decreased after Gyps treatment. The active mitosis of fibroblasts is one of the key processes in the pathogenesis of fibrotic diseases. RNA-seq showed that Gyps significantly inhibited mitosis and induced the G2/M phase cell cycle arrest. The mTOR/c-Myc axis plays an important role in the pathological process of pulmonary fibrosis. RNA-seq also demonstrated that Gyps inhibited the mTOR and c-Myc signaling in pulmonary fibrosis mice, which was further validated by Western blot and immunohistochemistry. AKT functions as an upstream molecule that regulates mTOR. Our western blot data showed that Gyps could suppress the activation of AKT. In conclusion, Gyps exerted anti-pulmonary fibrosis activity by inhibiting the AKT/mTOR/c-Myc pathway.

Keywords: AKT; c-Myc; gypenosides; mTOR; pulmonary fibrosis.