Bombyx batryticatus extract activates coagulation factor Ⅻ to promote angiogenesis in rats with cerebral ischemia/reperfusion injury

Abstract

Ethnopharmacological relevanceBombyx batryticatus is traditionally used to treat patients with stroke, but its mechanism remains unclear. Aim of the studyTo explore the interventional effect of Bombyx batryticatus extract as an activator of FⅫ on angiogenesis of rats with cerebral ischemia/reperfusion injury. Materials and methodsFirstly, the mechanism of Bombyx batryticatus interfering with IS was predicted by systematic pharmacology method, and then it was further verified by animal experiments. The effects of Bombyx batryticatus extract on plasma coagulation were detected, and the activation of coagulation factor Ⅻ (FⅫ) and its downstream substrate kallikrein kinase (KK) was detected in vitro. The brain morphology and expressions of FXII, KK, vascular endothelial growth factors (VEGF), CD31, Brdu/von Willebrand Factor (vWF) were detected. The morphological changes, cell proliferation and VEGF expression of brain microvascular endothelial cells were detected by oxygen glucose deprivation model. The pharmacodynamic substances of Bombyx batryticatus extract were identified by Liquid Chromatography - Mass Spectrometry (LC-MS). ResultsThe results of systematic pharmacology found that the treatment of IS by Bombyx batryticatus may be related to blood coagulation and other processes. In vitro, Bombyx batryticatus extract prolonged the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) (P < 0.05), activated FⅫ and promoted the production of downstream substrate KK, with dose-dependent (P < 0.05). Bombyx batryticatus extract improved the neuronal damage of rats, activated FXII and increased the production of KK and the expressions of VEGF, CD31, Brdu/vWF (P < 0.05). Bombyx batryticatus extract also increased the proliferation of brain microvascular endothelial cells and expression of VEGF in rats (P < 0.05). A total of 809 metabolites in Bombyx batryticatus extract were identified by LC-MS. ConclusionBombyx batryticatus extract may ameliorate the injury of nerve function in rats with cerebral ischemia/reperfusion injury.