Background: Ginkgetin, a flavonoid extracted from ginkgo biloba, has been shown to exhibit broad anti-inflammatory, anticancer, and antioxidative bioactivity. The extract of Ginkgo folium has been reported on attenuating bleomycin-induced pulmonary fibrosis, but the anti-fibrotic effects of ginkgetin is 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) were administrated intragastrically daily for 14 consecutive days. In vitro, the AMPK-siRNA transfection in primary lung fibroblasts further verified the regulation 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 nintedanib (40 mg/kg). AMPK-siRNA transfection in primary lung fibroblasts markedly blocked TGF-1-induced myofibroblasts transdifferentiation and abolished oxidative stress.
Conclusions: All these results suggested that ginkgetin exerted the ameliorative effects on bleomycin-induced oxidative stress and lung fibrosis mainly through an AMPK-dependent manner.
