Biomedical Research

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
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