Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro

Autor: Yuqin Zhang, Yajun Cao, Yan Li, Lijuan Xiao, Wei Xu, Wen Xu, Mei Huang, Xiaoqin Zhang, Yaping Chen, Lihong Nan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Pharmaceutical Biology, Vol 61, Iss 1, Pp 779-789 (2023)
Druh dokumentu: article
ISSN: 13880209
1744-5116
1388-0209
DOI: 10.1080/13880209.2023.2204142
Popis: AbstractContext Gualou Guizhi decoction (GLGZD) is an ancient Chinese classical prescription widely used to treat ischemic stroke. However, the molecular mechanisms of GLGZD promoting angiogenesis are unavailable.Objective This study investigates the angiogenesis effect of GLGZD as well as its mechanism.Materials and methods Ischemic stroke was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in male Sprague-Dawley (SD) rats. The GLGZD groups received GLGZD (3.6, 7.2 and 14.4 g/kg) orally. Oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in HUVECs receiving GLGZD medicated serum (MS). MRI, H&E staining, qRT-PCR, western blot and immunofluorescence methods were employed. miRNA210 inhibitor was employed to confirm the effects of GLGZD on promoting angiogenesis. Dual luciferase assay was used to verify the binding of miRNA210 with HIF mRNA.Results GLGZD treatment improved neurological function (by 27%), alleviated neuronal injury (by 76%), reduced infarct volume (by 74%) and increased microvessel density (by fourfold) in vivo. In vitro data had also shown that GLGZD caused proliferation of the cells (by 58%), their migration, and eventual formation of tubes (by threefold). Simultaneously, GLGZD enhanced the levels of angiogenesis-related molecules and activated the HIF/VEGF signalling pathway. Surprisingly, the beneficial effects of GLGZD on post-stroke angiogenesis and neurological recovery were weakened by miRNA210 inhibitor, and also abolished the mediation of proangiogenic factors. miRNA210 directly targeted HIF mRNA.Discussion and conclusions GLGZD enhances angiogenesis via activation of the miRNA210/HIF/VEGF signalling pathway, suggesting it can be a novel application as an effective angiogenic formula for stroke recovery.
Databáze: Directory of Open Access Journals
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