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  • the Korean Society for Brain and Neural Sciences

Article

Original Article

Exp Neurobiol 2021; 30(6): 401-414

Published online December 31, 2021

https://doi.org/10.5607/en21006

© The Korean Society for Brain and Neural Sciences

Oleanolic Acid Inhibits Neuronal Pyroptosis in Ischaemic Stroke by Inhibiting miR-186-5p Expression

Shi-Chang Cai1†, Xiu-Ping Li2†, Xing Li3†, Gen-Yun Tang4, Li-Ming Yi1 and Xiang-Shang Hu1*

1Department of Human Anatomy, School of Basic Medical Sciences, Hunan University of Medicine, Huaihua 418000, 2School of Public Health and Laboratory Medicine, Hunan University of Medicine, Huaihua 418000, 3School of Basic Medical Sciences, Shaoyang University, Shaoyang 422000, 4Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hunan University of Medicine, Huaihua 418000, Hunan Province, P.R. China

Correspondence to: *To whom correspondence should be addressed.
TEL: 86-13974582851, FAX: 86-13974582851
e-mail: yzhxs@126.com
These authors contributed equally to this article.

Received: March 22, 2021; Revised: November 26, 2021; Accepted: December 2, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Ischaemic stroke is a common condition leading to human disability and death. Previous studies have shown that oleanolic acid (OA) ameliorates oxidative injury and cerebral ischaemic damage, and miR-186-5p is verified to be elevated in serum from ischaemic stroke patients. Herein, we investigated whether OA regulates miR-186-5p expression to control neuroglobin (Ngb) levels, thereby inhibiting neuronal pyroptosis in ischaemic stroke. Three concentrations of OA (0.5, 2, or 8 μM) were added to primary hippocampal neurons subjected to oxygen–glucose deprivation/reperfusion (OGD/R), a cell model of ischaemic stroke. We found that OA treatment markedly inhibited pyroptosis. qRT–PCR and western blot revealed that OA suppressed the expression of pyroptosis-associated genes. Furthermore, OA inhibited LDH and proinflammatory cytokine release. In addition, miR-186-5p was downregulated while Ngb was upregulated in OA-treated OGD/R neurons. MiR-186-5p knockdown repressed OGD/R-induced pyroptosis and suppressed LDH and inflammatory cytokine release. In addition, a dual luciferase reporter assay confirmed that miR-186-5p directly targeted Ngb. OA reduced miR-186-5p to regulate Ngb levels, thereby inhibiting pyroptosis in both OGD/R-treated neurons and MCAO mice. In conclusion, OA alleviates pyroptosis in vivo and in vitro by downregulating miR-186-5p and upregulating Ngb expression, which provides a novel theoretical basis illustrating that OA can be considered a drug for ischaemic stroke.

Graphical Abstract


Keywords: Ischaemic stroke, Oleanolic acid, miR-186-5p, Neuroglobin, Pyroptosis