Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Evaluation of anisodamine-mediated amelioration of hypoxic injury in brain microvascular endothelial cells

Jing Wang¹, Qinghua Zhu², Xiaohui Duan³, Lingyu Li⁴, Shuyan Zhang⁵, Jie Chen⁶, Youming Wang¹

¹Department of Neurology; ²Department of Neurosurgery; ³Department of Otolaryngology; ⁴Department of Dermatology; ⁵Department of Pediatrics; ⁶Department of Anesthesiology, Affiliated Hospital of Hebei University of Engineering, Handan 056029, PR China.

For correspondence:- Youming Wang Email: xencheng33729@163.com

Accepted: 30 June 2021 Published: 29 July 2021

Citation: Wang J, Zhu Q, Duan X, Li L, Zhang S, Chen J, et al. Evaluation of anisodamine-mediated amelioration of hypoxic injury in brain microvascular endothelial cells. Trop J Pharm Res 2021; 20(7):1425-1432 doi: 10.4314/tjpr.v20i7.15

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the therapeutic effect of anisodamine on hypoxic injury of brain microvascular endothelial cells, and the underlying mechanism of action.

Methods: A hypoxic injury model of rat primary brain microvascular endothelial cells was established. Cell viability, proliferation, percent survival and apoptosis were assessed using MTT, EdU staining, trypan blue staining and TUNEL staining assays, respectively. The activities of lactate dehydrogenase (LDH) and matrix metalloproteinase-9 (MMP-9) were measured using colorimetry and enzyme-linked immunosorbent assay (ELISA), respectively. expression levels of key proteins in the PI3K/Akt signal route were determined by Western blotting.

Results: Anisodamine treatment significantly reduced apoptosis and LDH leakage in the rat cerebral vascular endothelial cell hypoxia injury model group (p < 0.001). At doses of 3 and 10 mM, anisodamine markedly reduced the cellular level of MMP-9 in rat cerebral vascular endothelial cell hypoxia injury model group (p < 0.001). Treatment of rat brain microvascular endothelial cells with anisodamine significantly reduced levels of caspase-3 and Bax, but up-regulated the expression levels of Bcl2, p-Akt and PI3K (p < 0.001).

Conclusion: Anisodamine exerts significant protective effect against hypoxic injury in rat brain microvascular endothelial cells by modulating PI3K/Akt signaling pathway. This finding provides a scientific basis for the clinical application of anisodamine in the treatment and prevention of ischemic cerebrovascular disease.

Keywords: Anisodamine, Stroke, Hypoxic injury, Brain microvascular endothelial cells