title: Protective effect of ginkgolide B against acute spinal cord injury in rats and its correlation with the Jak/STAT signaling pathway.
abstract: This study aimed to investigate the correlation between ginkgolide B (GB) and the JAK/STAT signaling pathway and to explore its regulating effect on secondary cell apoptosis following spinal cord injury (SCI), to elucidate the protective mechanism GB against acute SCI. Sprague-Dawley rats were randomly divided into a sham-operated group, an SCI group, an SCI + GB group, an SCI + methylprednisolone (MP) group, and an SCI + specific JAK inhibitor AG490 group. A rat model of acute SCI was established using the modified Allen's method. At 4 h, 12 h, 1 day, 3 days, 7 days and 14 days after injury, injured T10 spinal cord specimens were harvested. GB significantly increased inclined plane test scores and Basso, Beattie, and Bresnahan scale scores in SCI rats from postoperative day 3 to day 14. The effect was equal to that of the positive control drug, MP. Western blot analysis showed that JAK(2) was significantly phosphorylated from 4 h after SCI, peaked at 12 h and gradually decreased thereafter, accompanied by phosphorylation of STAT(3) with a similar time course. GB was shown to significantly inhibit the phosphorylation of JAK(2) and STAT(3) in rats with SCI. It significantly increased the ratio of B cell CLL/lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) protein expression at 24 h, led to an obvious down-regulation of caspase-3 gene and protein expression at 3 days, and significantly decreased the cell apoptosis index at each time point after SCI. This effect was similar to that obtained with the JAK-specific inhibitor, AG490. Our experimental findings indicated that GB can protect rats against acute SCI, and that its underlying mechanism may be related to the inhibition of JAK/STAT signaling pathway activation, improvement of the Bcl-2/Bax ratio, decreased caspase-3 gene and protein expression and further inhibition of secondary cell apoptosis following SCI.
authors.affiliation: Department of Orthopaedics, Hospital of Zhejiang General Corps of Armed Police Forces, Jiaxing, 314000, Zhejiang Province, People's Republic of China.
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Song
authors.forename: Zhongyou
authors.initials: Z
authors.lastname: Zeng
authors.forename: Caiyi
authors.initials: C
authors.lastname: Jin
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Zhang
authors.forename: Baoyue
authors.initials: B
authors.lastname: Ding
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation; D046934:Ginkgolides / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000378:metabolism; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020032:Tyrphostins / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D046934:Ginkgolides; D007783:Lactones; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D051028:bcl-2-Associated X Protein; C045856:ginkgolide B; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D053148:Caspase 3; D008775:Methylprednisolone