Przewaquinone A inhibits Angiotensin II-induced endothelial diastolic dysfunction activation of AMPK

被引：6

作者：

Chen, Si ^{[1
,2
]}

Xie, Jun-di ^{[1
]}

Xie, Meng-ting ^{[1
]}

Yang, Li-ning ^{[1
]}

Lin, Yu-Fang ^{[3
]}

Chen, Jun-Bang ^{[1
]}

Chen, Ting-fang ^{[1
]}

Zeng, Ke-feng ^{[1
]}

Tan, Zhang-Bin ^{[1
]}

Lu, Si-min ^{[1
]}

Wang, Hui-juan ^{[1
]}

Yang, Bo ^{[1
]}

Jiang, Wei-hao ^{[1
]}

Zhang, Shuang-wei ^{[1
]}

Deng, Bo ^{[1
]}

Liu, Bin ^{[1
]}

Zhang, Jingzhi ^{[1
]}

机构：

[1] Guangzhou Med Univ, Affiliated Hosp 2, Inst Integrat Tradit & Western Med, Dept Tradit Chinese Med,State Key Lab Resp Dis, Changgang East Rd 250, Guangzhou 510260, Peoples R China

[2] Hong Kong Baptist Univ HKBU, Sch Chinese Med, Kowloon Tong, Kowloon, Hong Kong, Peoples R China

[3] Guangzhou Med Univ, Clin Sch 2, Guangzhou 510260, Peoples R China

来源：

PHYTOMEDICINE | 2024年 / 133卷

基金：

中国国家自然科学基金;

关键词：

Przewaquinone A; AMPK; Endothelial dysfunction; Hypertension; MECHANISM;

D O I：

10.1016/j.phymed.2024.155885

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Background: Endothelial dysfunction (ED), characterized by markedly reduced nitric oxide (NO) bioavailability, vasoconstriction, and a shift toward a proinflammatory and prothrombotic state, is an important contributor to hypertension, atherosclerosis, and other cardiovascular diseases. Adenosine 5 '-monophosphate (AMP)-activated protein kinase (AMPK) is widely involved in cardiovascular development. Przewaquinone A (PA), a lipophilic diterpene quinone extracted from Salvia przewalskii Maxim, inhibits vascular contraction. Purpose: Herein, the goal was to explore the protective effect of PA on ED in vivo and in vitro, as well as the underlying mechanisms. Methods: A human umbilical vein endothelial cell (HUVEC) model of ED induced by angiotensin II (AngII) was used for in vitro observations. Levels of AMPK, endothelial nitric oxide synthase (eNOS), vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO), and endothelin-1 (ET-1) were detected by western blotting and ELISA. A mouse model of hypertension was established by continuous infusion of AngII (1000 ng/kg/min) for 4 weeks using osmotic pumps. Following PA and/or valsartan administration, NO and ET-1 levels were measured. The levels of AMPK signaling-related proteins in the thoracic aorta were evaluated by immunohistochemistry. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured using the tail cuff method. Isolated aortic vascular tone measurements were used to evaluate the vasodilatory function in mice. Molecular docking, molecular dynamics, and surface plasmon resonance imaging (SPRi) were used to confirm AMPK and PA interactions. Results: PA inhibited AngII-induced vasoconstriction and vascular adhesion as well as activated AMPK signaling in a dose-dependent manner. Moreover, PA markedly suppressed blood pressure, activated vasodilation in mice following AngII stimulation, and promoted the activation of AMPK signaling. Furthermore, molecular simulations and SPRi revealed that PA directly targeted AMPK. AMPK inhibition partly abolished the protective effects of PA against endothelial dysfunction. Conclusion: PA activates AMPK and ameliorates endothelial dysfunction during hypertension.

引用

页数：12

共 49 条

[21] Reduced FOXF1 links unrepaired DNA damage to pulmonary arterial hypertension [J].