2. Academic Validation
  3. 1,8-Cineole ameliorates endothelial injury and hypertension induced by L-NAME through regulation of autophagy via PI3K/mTOR signaling pathway

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

  • Eur J Pharmacol. 2023 Jun 26;175863. doi: 10.1016/j.ejphar.2023.175863.
Meng Chen 1,  Qilan Hu 1,  Shengquan Wang 1,  Ling Tao 2,  Xiaoxia Hu 3,  Xiangchun Shen 4
Affiliations

Affiliations

  • 1 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China; The Department of Pharmacology of Materia Medica (The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability), School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City-Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.
  • 2 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City-Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.
  • 3 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China; The Department of Pharmacology of Materia Medica (The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability), School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City-Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China. Electronic address: 251982143@qq.com.
  • 4 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China; The Department of Pharmacology of Materia Medica (The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability), School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources (The Union Key Laboratory of Guiyang City-Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China; The Key Laboratory of Endemic and Ethnic Diseases of Ministry of Education, Guizhou Medical University, Guiyang, China; The Department of Pharmacology, College of Basic Medical Sciences of Guizhou Medical University, Guiyang, China. Electronic address: shenxiangchun@126.com.
PMID: 37380045 DOI: 10.1016/j.ejphar.2023.175863
Abstract

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-Cinceole 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 L-nitroarginine 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 CQ 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 regulatiing of PI3K/mTOR.

Keywords

1,8-Cineole; Autophagy; Endothelial injury; Hypertension; PI3K/mTOR signaling pathway.

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