Ginkgo biloba Extract EGb761 Attenuates Bleomycin-Induced Experimental Pulmonary Fibrosis in Mice by Regulating the Balance of M1/M2 Macrophages and Nuclear Factor Kappa B (NF-κB)-Mediated Cellular Apoptosis
Ling Pan, Yuehong Lu, Zhanhua Li, Yuping Tan, Hongmei Yang, Ping Ruan, Ruixiang Li
Respiratory Medicine Department, Ruikang Hospital Affiliated to Guangxi Traditional Chinese Medicine University, Nanning, Guangxi, China (mainland)
Med Sci Monit 2020; 26:e922634
Available online: 2020-06-17
The aim of this study was to show whether the standardized Ginkgo biloba extract EGb761, a traditional Chinese medicine, has a therapeutic effect on pulmonary fibrosis (PF).
MATERIAL AND METHODS: Bleomycin (BLM) was used for establishing the PF mouse model. The mice were treated with a gradient of EGb761 for 28 days to determine an appropriate drug dose. On day 28, the effect of EGb761 on lung injury and inflammation was confirmed by hematoxylin and eosin and Masson staining and evaluated by pulmonary alveolitis and Ashcroft score. The balance of M1/M2 macrophages was evaluated with the respective markers inducible nitric oxide synthase and and interleukin-10 by real-time polymerase chain reaction. Furthermore, the expressions of fibrosis-associated protein alpha-smooth muscle actin (SMA), related inflammatory protein transforming growth factor (TGF)-ß1, the apoptosis-related proteins B-cell lymphoma-associated X protein (Bax), B-cell lymphoma (Bcl)-2, caspase-3, caspase-9, and phosphorylated nuclear factor (NF)-kappaB (p65) were assessed by western blot.
RESULTS: On day 28, PF was induced by treating with BLM, whereas EGb761 suppressed the PF of lung tissue. The BLM-induced imbalance of M1/M2 macrophages was reduced by EGb761. Furthermore, the increasing amounts of alpha-SMA and TGF-ß1 induced by BLM were suppressed by EGb761. In addition, the protein or messenger ribonucleic acid expression levels of phosphorylated NF-kappaB (p65), caspase-3, and caspase-9 were upregulated, whereas Bax and Bcl-2 were downregulated. Treatment with EGb761 restored the levels of these proteins except for caspase-9.
CONCLUSIONS: This study illustrated the protective effect of EGb761 on BLM-induced PF by regulating the balance of M1/M2 macrophages and NF-kappaB (p65)-mediated apoptosis. The results demonstrated the potential clinical therapeutic effect of EGb761, providing a novel possibility for curing PF.
Keywords: Apoptosis, Ginkgo biloba, idiopathic pulmonary fibrosis, Macrophages, Transcription Factor RelA