Zhao-Ma Shu1, Xiao-Dong Shu1, Hui-Qin Li2, Yi Sun2, Han Shan1, Xi-Yang Sun1, Ren-Hong Du1, Ming Lu1, Ming Xiao1, Jian-Hua Ding1, Gang Hu1,3. 1. Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China. 2. Chengdu Baiyu Pharmaceuticals Co., Ltd, 88 Keyuannan Road, Chengdu, Sichuan, 610041, China. 3. Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu, 210023, China.
Abstract
AIM: Ginkgolide B (GB) has shown neuroprotective effect in treating ischemic stroke, related to its property of anti-inflammation. Nevertheless, it is unclear whether GB is able to modulate microglia/macrophage polarization, which has recently been proven to be vital in the pathology of ischemic stroke. METHODS: We performed transient middle cerebral artery occlusion (tMCAO) on C57BL/6J male mice and induced cultured BV2 microglia and primary bone marrow-derived macrophages to be M1/2 phenotype by LPS+ interferon-γ and IL-4, respectively. Immunofluorescence and flow cytometry were used for detecting the specialized protein expression of M1/2, such as CD206 and CD16/32. qPCR was utilized to detect the signature gene change of M1/2. RESULTS: GB significantly reduced cerebral ischemic damage and ameliorated the neurological deficits of mice after tMCAO. More importantly, our experiments proved that GB promoted microglia/macrophage transferring from inflammatory M1 phenotype to a protective, anti-inflammatory M2 phenotype in vivo or vitro. CV3988 and silencing the platelet activator factor (PAF) receptor by siRNA demonstrated that PAF receptor was involved in the modulation of microglia/macrophage polarization. CONCLUSION: Our results reveal a novel pharmacological effect of GB in modulating microglia/macrophage polarization after tMCAO, thus deepening our understanding of neuroprotective mechanisms of GB in treatment of ischemic stroke. Furthermore, this new mechanism may allow GB to be used in many other microglia/macrophage polarization-related inflammatory diseases.
AIM: Ginkgolide B (GB) has shown neuroprotective effect in treating ischemic stroke, related to its property of anti-inflammation. Nevertheless, it is unclear whether GB is able to modulate microglia/macrophage polarization, which has recently been proven to be vital in the pathology of ischemic stroke. METHODS: We performed transient middle cerebral artery occlusion (tMCAO) on C57BL/6J male mice and induced cultured BV2 microglia and primary bone marrow-derived macrophages to be M1/2 phenotype by LPS+ interferon-γ and IL-4, respectively. Immunofluorescence and flow cytometry were used for detecting the specialized protein expression of M1/2, such as CD206 and CD16/32. qPCR was utilized to detect the signature gene change of M1/2. RESULTS:GB significantly reduced cerebral ischemic damage and ameliorated the neurological deficits of mice after tMCAO. More importantly, our experiments proved that GB promoted microglia/macrophage transferring from inflammatory M1 phenotype to a protective, anti-inflammatory M2 phenotype in vivo or vitro. CV3988 and silencing the platelet activator factor (PAF) receptor by siRNA demonstrated that PAF receptor was involved in the modulation of microglia/macrophage polarization. CONCLUSION: Our results reveal a novel pharmacological effect of GB in modulating microglia/macrophage polarization after tMCAO, thus deepening our understanding of neuroprotective mechanisms of GB in treatment of ischemic stroke. Furthermore, this new mechanism may allow GB to be used in many other microglia/macrophage polarization-related inflammatory diseases.
Authors: R Tanaka; M Komine-Kobayashi; H Mochizuki; M Yamada; T Furuya; M Migita; T Shimada; Y Mizuno; T Urabe Journal: Neuroscience Date: 2003 Impact factor: 3.590
Authors: Kwang Ho Lee; Jung Kyu Kim; Jae Sik Yu; Se Yun Jeong; Jin Hee Choi; Jin-Chul Kim; Yoon-Joo Ko; Seon-Hee Kim; Ki Hyun Kim Journal: Arch Pharm Res Date: 2021-04-30 Impact factor: 4.946