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, England, UK.
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, University Road, Abbottabad, KPK, 22060, Pakistan.
Eur J Pharmacol. 2020 Oct 5;884:173400. doi: 10.1016/j.ejphar.2020.173400. Epub 2020 Jul 27.
Diosmetin is a flavonoid present naturally in citrus fruit. Plants containing diosmetin have been reported to have anti-hypertensive and vasorelaxant effects. Therefore, experiments were carried out to study the effects of diosmetin in segments of the porcine coronary artery (PCA). PCA rings were mounted for isometric tension recording in isolated tissue baths and pre-contracted with the thromboxane A mimetic U46619 or KCl. Cumulative concentration response curves to diosmetin were then carried out in the presence or absence of inhibitors or activators of different signaling pathways. The effect on calcium channels was determined by investigating the effect of a single concentration of diosmetin (30 μM) on calcium-induced contractions or contractions to BAY K8644. Diosmetin caused a concentration-dependent relaxation after pre-contraction with U46619 or KCl, which was unaffected by removal of the endothelium. Tetraethylammonium (TEA), and 4-aminopyridine (4-AP), but not barium chloride, caused significant inhibition of the diosmetin-mediated vasorelaxation, indicating a role for potassium channels. Diosmetin inhibited calcium-induced contractions and contractions to the L-type calcium channel opener BAY K8644. Furthermore, diosmetin inhibited the contractions in response to caffeine, cyclopiazonic acid and ionomycin, indicating a general effect on calcium-induced contractions. Contractions in response to the protein kinase C (PKC) activator Phorbol 12-myristate 13-acetate (PMA) were also inhibited by diosmetin, suggesting that it may inhibit a calcium-activated PKC isoform. In summary, diosmetin produced significant vasodilatory effects. The data indicate a role for potassium channels as well as an effect on calcium-induced contractile pathways, possible through inhibition of PKC.
柚皮素是一种存在于柑橘类水果中的类黄酮。含有柚皮素的植物已被报道具有抗高血压和血管舒张作用。因此，进行了实验来研究柚皮素对猪冠状动脉（PCA）段的影响。PCA 环被安装在离体组织浴中进行等长张力记录，并通过血栓烷 A 模拟物 U46619 或 KCl 预收缩。然后在存在或不存在不同信号通路的抑制剂或激活剂的情况下进行柚皮素的累积浓度反应曲线。通过研究 30 μM 柚皮素对钙诱导收缩或 BAY K8644 收缩的单一浓度的影响来确定对钙通道的影响。柚皮素在 U46619 或 KCl 预收缩后引起浓度依赖性舒张，内皮去除后无影响。四乙铵（TEA）和 4-氨基吡啶（4-AP），但不是氯化钡，可显著抑制柚皮素介导的血管舒张，表明钾通道的作用。柚皮素抑制钙诱导的收缩和 L 型钙通道 opener BAY K8644 的收缩。此外，柚皮素抑制对咖啡因、环匹阿尼酸和离子霉素的收缩反应，表明对钙诱导的收缩有一般作用。对蛋白激酶 C（PKC）激活剂佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）的收缩反应也被柚皮素抑制，表明它可能抑制钙激活的 PKC 同工型。总之，柚皮素产生了显著的血管舒张作用。数据表明钾通道的作用以及对钙诱导的收缩途径的影响，可能通过抑制 PKC。
