Department of Pharmacy, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo; Institute of Pharmacology and Toxicology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
Institute of Pathophysiology, Faculty of Medicine, University of Prishtina, Prishtina, Kosovo.
Eur J Pharmacol. 2017 Sep 5;810:51-56. doi: 10.1016/j.ejphar.2017.06.004. Epub 2017 Jun 8.
The goal of this study was to test the effects of bioactive phenylpropanoid dibenzylbutyrolactone lignan arctigenin (ATG) in vascular tone. Human bypass graft vessel, from a saphenous vein (SV), were set up in organ bath system and contracted with potassium chloride (KCl, 40mM). Two concentration-response curves of noradrenaline (NE) (10nM-100μM) separated with an incubation period of 30min without (Control) or with ATG (3-100μM) were established. Inhibitors of nitric oxide, prostaglandins, K related channels or calcium influx were used to delineate the molecular mechanisms beyond ATG effects. To investigate anti-inflammatory actions, SV were treated with 10μM or 100μM ATG and incubated for 18h in the absence or presence of both interleukin-1beta (IL-1β) and lipopolysaccharide (LPS) to mimic the physiological or inflamed tissue conditions. Proatherogenic and inflammatory mediators İnterleukine-1 beta (IL-1β), Monocyte Chemoattractant Proteine-1 (MCP-1), Tumor Necrosis Factor- α (TNF-α), İnterleukine-6 (IL-6), Prostaglandin E (PGE) and İnterleukine-8 (IL-8) in the supernatant were measured. ATG significantly decreased vascular contractile response to NE. Moreover, it reduced contractions induced by KCl and cumulative addition of CaCl The mediators were significantly increased in inflammatory conditions compared to normal conditions, an effect which was inhibited by ATG (10 and 100µM). ATG reduces contractions in SV and decreases the production of proinflammatory-proatherogenic mediators, setting the stage for further evaluating the effect of ATG in cardiovascular diseases.
本研究旨在测试生物活性苯丙烷二苄基丁内酯木脂素（ATG）对血管张力的影响。采用器官浴系统建立人旁路移植血管（SV），用氯化钾（KCl，40mM）收缩。建立两个去甲肾上腺素（NE）（10nM-100μM）浓度反应曲线，中间间隔 30 分钟无（对照）或有 ATG（3-100μM）孵育期。使用一氧化氮、前列腺素、K 相关通道或钙内流抑制剂来描绘 ATG 作用之外的分子机制。为了研究抗炎作用，SV 用 10μM 或 100μM ATG 处理，在不存在或存在白细胞介素-1β（IL-1β）和脂多糖（LPS）的情况下孵育 18 小时，以模拟生理或炎症组织条件。上清液中促动脉粥样硬化和炎症介质白细胞介素-1β（IL-1β）、单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、前列腺素 E（PGE）和白细胞介素-8（IL-8）的含量。ATG 显著降低了血管对 NE 的收缩反应。此外，它还降低了 KCl 诱导的收缩和 CaCl 的累积添加。与正常条件相比，炎症条件下这些介质显著增加，而 ATG（10 和 100µM）抑制了这种增加。ATG 可减少 SV 的收缩并减少促炎-促动脉粥样硬化介质的产生，为进一步评估 ATG 在心血管疾病中的作用奠定了基础。
