Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
PLoS One. 2019 Sep 6;14(9):e0222101. doi: 10.1371/journal.pone.0222101. eCollection 2019.
Exaggerated vasoconstriction plays important roles in vascular complication in aging and many diseases like diabetes. Here, we investigated the protective effect of Psiadia punctulata (PP) on advanced glycation end products (AGEs)-induced aggravated vasoconstriction. The effect of total methanol extract of PP leaves (PPT) on AGE-induced vascular injury was studied through bioassay-guided fractionation procedures in order to find the bioactive fraction and isolate the bioactive compounds. Vascular reactivity was studied using the isolated artery technique by adding cumulative concentrations of phenylephrine (PE) or acetyl choline (ACh). In addition, the antiglycating effect, as well as the effect on AGEs intermediates dityrosine and N-formylkynurenine and their radical scavenging activity were measured. The results showed that PPT alleviated the AGEs-induced aggravated vasoconstriction in a concentration-dependent manner. The bioassay guided fractionation procedures suggested the chloroform fraction (Fr I) to be responsible for the activity. Chemical investigation of this fraction resulted in isolation of four major bioactive compounds that were identified as: umuhengerin (1), gardenin (2), luteolin-3,4-dimethyl ether (3), and 5,3-dihydroxy-6,7,4,5-tetramethoxyflavone (4). The four compounds alleviated the exaggerated vasoconstriction in a dose dependent manner. In search for their mechanism of action, we observed that PPT, Fr. I and the isolated compounds did not improve the impaired vasodilation associated with AGEs exposure. PPT, Fr. I and the isolated compounds 1-4 inhibited AGEs formation and their protein oxidation intermediates. Furthermore, PPT, Fr. I and the isolated compounds 1-4 showed weak radical scavenging activity with compound 4 as the most potent. In conclusion, PPT appears to protect against AGEs-induced exaggerated vasoconstriction through antiglycation and radical scavenging activities.
Psiadia punctulata（PP）叶总甲醇提取物通过生物测定指导的分步分离程序对 AGE 诱导的血管损伤的保护作用进行了研究，以找到生物活性部分并分离生物活性化合物。使用添加累积浓度的苯肾上腺素（PE）或乙酰胆碱（ACh）的离体动脉技术研究血管反应性。此外，还测量了抗糖化作用以及对 AGE 中间体二酪氨酸和 N-甲酰基犬尿氨酸及其自由基清除活性的影响。结果表明，PPT 以浓度依赖的方式减轻 AGE 诱导的血管收缩加剧。生物测定指导的分步分离程序表明，氯仿部分（Fr I）负责该活性。对该部分的化学研究导致分离出四个主要的生物活性化合物，它们分别被鉴定为：umuhengerin（1），gardenin（2），木犀草素-3，4-二甲醚（3）和 5,3-二羟基-6,7,4`-三甲氧基黄酮（4）。这四种化合物以剂量依赖性方式减轻了夸张的血管收缩。在寻找其作用机制时，我们观察到 PPT、Fr.I 和分离出的化合物并没有改善与 AGEs 暴露相关的血管舒张受损。PPT、Fr.I 和分离出的化合物 1-4 抑制 AGEs 的形成及其蛋白氧化中间体。此外，PPT、Fr.I 和分离出的化合物 1-4 显示出较弱的自由基清除活性，其中化合物 4 最强。总之，PPT 似乎通过抗糖化和自由基清除活性来防止 AGE 诱导的夸张血管收缩。
