Puerarin induces mouse mesenteric vasodilation and ameliorates hypertension involving endothelial TRPV4 channels. Issue 11 (6th November 2020)

• Record Type: Journal Article
• Authors: Zhou, Tingting; Wang, Zhiwei; Guo, Mengting; Zhang, Ka; Geng, Li; Mao, Aiqin; Yang, Yujiao; Yu, Fan
• Is Part Of: Food & function. Volume 11:Issue 11(2020)
• Page Start: 10137
• Page End: 10148
• Publication Date: 2020-11-06
• Subjects: Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; Nutrition -- Periodicals; 664.07
• DOI: 10.1039/d0fo02356f
• Languages: English
• ISSNs: 2042-6496

Abstract

Abstract : Puerarin derived from Pueraria induces mesenteric endothelium-dependent vasodilation involving the TRPV4-IKCa /SKCa pathway, exhibiting antihypertensive activity against high-salt-induced hypertension. Abstract : Puerarin (Pue) is an isoflavone derived from the root of Pueraria lobata, which has been widely used as food and a herb for treating cardiovascular and cerebrovascular diseases. Transient receptor potential vanilloid 4 (TRPV4), a Ca 2+ -permeable channel with multiple modes of activation, plays an important role in vascular endothelial function and vasodilation. However, no reports have shown the effects of Pue on TRPV4 channels and mouse small mesenteric arteries. In the present study, we performed a molecular docking assay by using Discovery Studio 3.5 software to predict the binding of Pue to TRPV4 protein. The activation of TRPV4 by Pue was determined by intracellular Ca 2+ concentration ([Ca 2+ ]i ), live-cell fluorescent Ca 2+ imaging and patch clamp assays. Molecular docking results indicated a high possibility of Pue–TPRV4 binding. [Ca 2+ ]i and Ca 2+ imaging assays showed that Pue activated TRPV4 channels and increased [Ca 2+ ]i in TRPV4-overexpressing HEK293 (TRPV4-HEK293) cells and primary mouse mesenteric artery endothelial cells (MAECs). Patch clamp assay demonstrated that Pue stimulated the TRPV4-mediated cation currents. Additionally, Pue relaxed mouse mesenteric arteries involving the TRPV4-small-conductance Ca 2+ -activated K + channel (SKCa )/intermediate-conductance Ca 2+ -activated K + channel (IKCa ) pathway, and reduced systolic blood pressure (SBP) in high-salt-induced hypertensive mice. Our study found for the first time that Pue acts as a TRPV4 agonist, induces endothelium-dependent vasodilation in mouse mesenteric arteries, and attenuates blood pressure in high-salt-induced hypertensive mice, highlighting the beneficial effect of Pue in treating endothelial dysfunction-related cardiovascular diseases.