1,8-Cineole ameliorates endothelial injury and hypertension induced by L-NAME through regulation of autophagy via PI3K/mTOR signaling pathway.

Meng Chen, Qilan Hu, Shengquan Wang, Ling Tao, Xiaoxia Hu, Xiangchun Shen

European journal of pharmacology 2023 Sep 05

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Our previous data confirmed that 1,8-Cineole had an antihypertensive effect in animal models. However, it is unclear whether antihypertension is dependent on the protective effect of 1,8-Cineole on endothelial function and structure. At present, the purpose was to investigate the protective effects of 1,8-Cineole on vascular endothelial tissue in hypertensive rats and human umbilical vein endothelial cells (HUVECs). Our results showed that 1,8-Cineole significantly reduced the blood pressure and improved the vascular endothelial lesion, attenuated vascular oxidative stress and inflammation induced by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) in rats. Pretreatment with 1,8-Cineole was able to inhibit the increase in malondialdehyde (MDA) and reactive oxygen species (ROS) induced by L-NAME, and increased the release and expression of superoxide dismutase (SOD) and nitric oxide (NO). In addition, 1,8-Cineole also reversed the increase of autophagy-associated protein LC3Ⅱ/LC3Ⅰ and the decrease of P62 in vivo and in vitro respectively. There was a synergistic effect between PI3K agonists and drugs, while PI3K inhibitors blocked the efficacy of 1,8-Cineole. The addition of autophagy inhibitor chloroquine increases the expression of eNOS. Taken together, our results indicate that 1,8-Cineole has potential beneficial promising antihypertension depending on the integrity of vascular endothelial structure and function induced by L-NAME, and the mechanism involves ameliorating autophagy by regulating of PI3K/mTOR. Copyright © 2023 Elsevier B.V. All rights reserved.

Citation

Meng Chen, Qilan Hu, Shengquan Wang, Ling Tao, Xiaoxia Hu, Xiangchun Shen. 1,8-Cineole ameliorates endothelial injury and hypertension induced by L-NAME through regulation of autophagy via PI3K/mTOR signaling pathway. European journal of pharmacology. 2023 Sep 05;954:175863