Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, University Road, Abbottabad, KPK-22060, Pakistan; Department of Pharmacology, College of Pharmacy, University of Sargodha, University Road, Sargodha, Punjab, 40100, Pakistan; School of Life Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, University Road, Abbottabad, KPK-22060, Pakistan.
Eur J Pharmacol. 2020 Jan 5;866:172815. doi: 10.1016/j.ejphar.2019.172815. Epub 2019 Nov 17.
Juglone (5-hydroxy-1, 4-naphthoquinone), is a natural phenolic compound that has been shown to relax smooth muscle. Therefore the aim of this study was to determine the effect of juglone on vascular tone using porcine coronary artery (PCA). Segments of PCA, with or without endothelium, were mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane A analog U46619 or KCl. After pre-contraction, cumulative concentrations of juglone were added to the tissues, in the presence or absence of a variety of inhibitors on intracellular signaling pathways. Juglone (10 to 10 M) produced a concentration-dependent relaxation of the PCA which was reduced in endothelium-denuded vessels, as well as in vessels pre-treated with the nitric oxide synthase inhibitor L-NAME, indicating that at least part of the effect of juglone is mediated through an endothelium, NO-dependent mechanism. Juglone also inhibited contractions in response to influx of extracellular calcium and release of intracellular calcium, indicating that juglone may inhibit a common signaling pathway downstream of calcium. Contractions to the protein kinase C activator Phorbol 12-myristate 13-acetate were also reduced by juglone, suggesting that juglone might be acting through inhibition of protein kinase C. In summary, juglone produces a relaxation of the porcine coronary artery through activation of the nitric oxide pathway and inhibition of calcium-induced contractions.
胡桃醌（5-羟基-1,4-萘醌）是一种天然酚类化合物，已被证明可使平滑肌松弛。因此，本研究旨在使用猪冠状动脉（PCA）来确定胡桃醌对血管张力的影响。在分离的组织浴中，对具有或不具有内皮的 PCA 段进行等长张力记录的安装，并使用血栓烷 A 类似物 U46619 或 KCl 预收缩。预收缩后，在存在或不存在各种细胞内信号通路抑制剂的情况下，将累积浓度的胡桃醌添加到组织中。胡桃醌（10 至 10M）产生了 PCA 的浓度依赖性松弛，在内皮缺失的血管以及用一氧化氮合酶抑制剂 L-NAME 预处理的血管中，这种松弛作用减弱，表明胡桃醌的至少部分作用是通过内皮介导的，NO 依赖性机制。胡桃醌还抑制了对外源钙流入和细胞内钙释放的反应性收缩，表明胡桃醌可能抑制了钙下游的共同信号通路。蛋白激酶 C 激活剂佛波醇 12-肉豆蔻酸 13-乙酸酯的收缩也被胡桃醌抑制，表明胡桃醌可能通过抑制蛋白激酶 C 起作用。总之，胡桃醌通过激活一氧化氮途径和抑制钙诱导的收缩来产生猪冠状动脉的松弛。
