title: Activations of GABAergic signaling, HSP70 and MAPK cascades are involved in baicalin's neuroprotection against gerbil global ischemia/reperfusion injury.
abstract: Baicalin, a flavonoid compound isolated from the plant Scutellaria baicalensis Georgi, is known as a protective agent against delayed neuronal cell death after ischemia/reperfusion. To investigate the neuroprotective mechanism of baicalin, the present study was conducted to explore whether the alterations of GABAergic signaling, heat shock protein 70 (HSP70) and mitogen-activated protein kinases (MAPKs) were involved in its neuroprotection on gerbils global ischemia. The bilateral carotid arteries were occluded by 5 min and baicalin at the dose of 200 mg/kg was intraperitoneally injected into the gerbils immediately after cerebral ischemia. Seven days after reperfusion, neurological deficit was scored and changes in hippocampal neuronal cell death were assessed by Nissl staining as well as NeuN immunohistochemistry. The mRNA and protein expressions of GABAergic signal molecules (GABA(A)R α1, GABA(A)R γ2, KCC2 and NKCC1) were determined in ischemic hippocampus by real-time RT-PCR and Western blot, respectively. In addition, HSP70 and MAPKs cascades (ERK, JNK and p38) were also detected using western blot assay. Our results illustrated that baicalin treatment significantly facilitated neurological function, suppressed the ischemia-induced neuronal damage. Besides, administration of baicalin also caused a striking increase of GABA(A)R α1, GABA(A)R γ2 and KCC2 together with the decrease of NKCC1 at mRNA and protein levels in gerbils hippocampus following an ischemic insult. Furthermore, the protein expressions of HSP70 and phosphorylated ERK (p-ERK) were evidently augmented while the phosphorylated JNK (p-JNK) and phosphorylated p38 (p-p38) were strikingly diminished in ischemic gerbils with baicalin treatment. These findings suggest that baicalin activates GABAergic signaling, HSP70 and MAPKs cascades in global ischemia, which may be a mechanism underlying the baicalin's neuroprotection.
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Dai
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Yong-Ming
authors.initials: YM
authors.lastname: Qiu
authors.forename: Shan-Quan
authors.initials: SQ
authors.lastname: Li
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Xiong
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Yin
authors.forename: Feng
authors.initials: F
authors.lastname: Jia
authors.forename: Ji-Yao
authors.initials: JY
authors.lastname: Jiang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005419:Flavonoids / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D005849:Gerbillinae; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D005419:Flavonoids; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D010751:Phosphopyruvate Hydratase; D018079:Receptors, GABA; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters; C038044:baicalin