Biomedical Research

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.

Research Article - Biomedical Research (2018) Volume 29, Issue 1

Effect of Ilexonin A on the Notch signaling pathway following cerebral ischemia-reperfusion in rats

Ilexonin A is a pentacyclic triterpenes, extracted from the herb Ilex pubescens with anti-thrombosis and anti-inflammatory activity, and improves blood circulation. This study determines whether Ilexonin A (IA) activates Notch signaling to induce neurogenesis following cerebral ischemia-reperfusion injury. We investigated the effect of Ilexonfound in the Ilexonin A-treatedin A on post-ischemic proliferation and differentiation of neural stem cells. Male Sprague-Dawley rats were divided into four groups: normal (n=6), sham-operated (n=6), control (n=24), and IA-treated (n=24). Focal cerebral ischemia-reperfusion injury was induced by the Middle Cerebral Artery Occlusion (MCAO) method. Ilexonin A at dose of 40 mg/kg was administered via intraperitoneal injection immediately following MCAO and then once daily until the rats were sacrificed. 5-bromo 2-deoxyuridine labeled proliferating cells and neurogenesis and Notch induction in the ischemic tissue perienchyma were observed at d 1, 3, 7, and 14 following ischemia by immunohistochemistry. NICD protein, Notch1, PS1, and HES1 gene expression was detected. Ilexonin A decreased the infarct volume and improved neurological deficits in a time-dependent manner. A higher number of Brdu/Nestin double-positive cells was found in the Ilexonin A-treated rats, compared with the rats exposed to ischemia only at both 3 d (14.33 ± 1.63 vs. 11.33 ± 1.21, *p<0.05) and 7 d (29.33 ± 2.58 vs. 24.50 ± 2.7, *p<0.05). Ilexonin A activates Notch signaling by increasing the expression of NICD at both 3 d (75.83 ± 1.94 vs. 69.67 ± 3.93, #p<0.01) and 7 d (53.67 ± 2.42 vs. 50.17 ± 2.93, #p<0.01). Ilexonin A also increased the gene expression levels of Notch1, PS1, and HES1 at 3 d after reperfusion in the rats. These findings suggested that the protective effects of Ilexonin A were associated with neuronal regeneration, and the inactivation of Notch signaling pathways.

Author(s): Yu Han, Guan-Yi Zheng, Bi-Qin Zhang, Xiao-Dong Chen, Qiong Jiang

Abstract Full Text PDF