Research Paper Volume 13, Issue 11 pp 15353—15365
Alisol A 24-acetate protects against brain microvascular endothelial cells injury through inhibiting miR-92a-3p/tight junctions axis
- 1 The Affiliated Rehabilitation Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou 350003, China
- 2 College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350112, China
Received: October 14, 2020 Accepted: May 11, 2021 Published: June 4, 2021https://doi.org/10.18632/aging.203094
How to Cite
Copyright: © 2021 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Blood brain barrier (BBB) dysfunction developed with aging is related to brain microvascular endothelial cells (BMECs) injury and losses of tight junctions (TJs). In the present study, we found that Alisol A 24-acetate (AA), a natural compound frequently used as treatment against vascular diseases was essential for BMECs injury and TJs degradation. Our experimental results showed that AA enhanced cell viability and increased zonula occludens-1 (ZO-1), claudin-5, and occludin expression in the oxygen-glucose deprivation (OGD)-induced BMECs. The exploration of the underlying mechanism revealed that AA restrained miR-92a-3p, a noncoding RNA involved in endothelial cells senescence and TJs impairment. To test the role of the miR-92a-3p in BMECs, the cells were transfected with miR-92a-3p mimics and inhibitor. The results showed that miR-92a-3p mimics inhibited cell viability and elevated lactate dehydrogenase (LDH) levels as well as suppressed ZO-1, claudin-5 and occludin expression, while the miR-92a-3p inhibitor reversed the above results. These findings were similar to the therapeutic effects of AA in the OGD-induced BMECs. Bioinformatics analysis and dual-luciferase assay confirmed ZO-1 and occludin were the target genes of miR-92a-3p mediated AA protective roles. In summary, the data demonstrated that AA protected against BMECs damage and TJs loss through the inhibition of miR-92a-3p expression. This provided evidence for AA application in aging-associated BBB protection.