Ginkgolide B Protects Against Ischemic Stroke Via Modulating Microglia Polarization in Mice.
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.



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.



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.



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.
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Zhao-Ma
ZM
Shu
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Xiao-Dong
XD
Shu
Chengdu Baiyu Pharmaceuticals Co., Ltd, 88 Keyuannan Road, Chengdu, Sichuan, 610041, China.
Hui-Qin
HQ
Li
Chengdu Baiyu Pharmaceuticals Co., Ltd, 88 Keyuannan Road, Chengdu, Sichuan, 610041, China.
Yi
Y
Sun
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Han
H
Shan
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Xi-Yang
XY
Sun
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Ren-Hong
RH
Du
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Ming
M
Lu
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Ming
M
Xiao
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
Jian-Hua
JH
Ding
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, China.|Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu, 210023, China.
Gang
G
Hu
D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D015687:Cell Hypoxia / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D046934:Ginkgolides / Q000494:pharmacology* / Q000627:therapeutic use*; D005947:Glucose / Q000172:deficiency; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism
D017077:Culture Media, Conditioned; D016207:Cytokines; D004791:Enzyme Inhibitors; D046934:Ginkgolides; D007783:Lactones; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; C045856:ginkgolide B; D005947:Glucose
Ginkgolide B; Microglia/macrophage polarization; Platelet activator factor receptor; Stroke