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

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.

• Authors: Guoqing Ren, Gonghao Xu, Renshi Li, Haifeng Xie, Zhengguo Cui, Lei Wang, Chaofeng Zhang
• Journal: Current molecular pharmacology (Curr Mol Pharmacol) Vol. 16 Issue 2 Pg. 217-227 ( 2023) ISSN: 1874-4702 [Electronic] United Arab Emirates
• PMID: 35249515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• AMP-Activated Protein Kinases
• Bleomycin
• ginkgetin
• Biflavonoids

Topics

• Animals
• Mice
• AMP-Activated Protein Kinases
• Bleomycin (pharmacology)
• Lung (pathology)
• Oxidative Stress (drug effects)
• Pulmonary Fibrosis (chemically induced, drug therapy, pathology)
• Biflavonoids (pharmacology, therapeutic use)