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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Modulation of Bleomycin-induced Oxidative Stress and Pulmonary Fibrosis by Ginkgetin in Mice via AMPK

Author(s): Guoqing Ren, Gonghao Xu, Renshi Li, Haifeng Xie, Zhengguo Cui, Lei Wang* and Chaofeng Zhang*

Volume 16, Issue 2, 2023

Published on: 27 May, 2022

Article ID: e040322201686 Pages: 11

DOI: 10.2174/1874467215666220304094058

Price: $65

Abstract

Background: Ginkgetin, a flavonoid extracted from Ginkgo biloba, has been shown to exhibit broad anti-inflammatory, anticancer, and antioxidative bioactivity. Moreover, the extract of Ginkgo folium has been reported on attenuating bleomycin-induced pulmonary fibrosis, but the anti-fibrotic effects of ginkgetin are still unclear. This study was intended to investigate the protective effects of ginkgetin against experimental pulmonary fibrosis and its underlying mechanism.

Methods: In vivo, bleomycin (5 mg/kg) in 50 μL saline was administrated intratracheally in mice. One week after bleomycin administration, ginkgetin (25 or 50 mg/kg) or nintedanib (40 mg/kg) was administrated intragastrically daily for 14 consecutive days. In vitro, the AMPK-siRNA transfection in primary lung fibroblasts further verified the regulatory effect of ginkgetin on AMPK.

Results: Administration of bleomycin caused characteristic histopathology structural changes with elevated lipid peroxidation, pulmonary fibrosis indexes, and inflammatory mediators. The bleomycin- induced alteration was normalized by ginkgetin intervention. Moreover, this protective effect of ginkgetin (20 mg/kg) was equivalent to that of nintedanib (40 mg/kg). AMPK-siRNA transfection in primary lung fibroblasts markedly blocked TGF-β1-induced myofibroblasts transdifferentiation and abolished oxidative stress.

Conclusion: All these results suggested that ginkgetin exerted ameliorative effects on bleomycininduced oxidative stress and lung fibrosis mainly through an AMPK-dependent manner.

Keywords: Ginkgetin, pulmonary fibrosis, oxidative stress, AMPK, Sirtuin 1, NADPH Oxidase 4.

Graphical Abstract

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