Ahmad Taseer, Javed Adil, Khan Taous, Althobaiti Yusuf S, Ullah Aman, Almutairi Farooq M, Shah Abdul Jabbar
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, University Road, Abbottabad 22060, Pakistan.
Laboratory of Cardiovascular Research and Integrative Pharmacology, College of Pharmacy, University of Sargodha, Sargodha 40100, Pakistan.
Pharmaceuticals (Basel). 2022 Jul 30;15(8):951. doi: 10.3390/ph15080951.
Diosmetin is a flavonoid that is found in many important medicinal plants that have antihypertensive therapeutic potential. Diosmetin has been shown to have antiplatelet, anti-inflammatory and antioxidant properties, which suggests that it could be a potential candidate for use in antihypertensive therapy.
In vivo and in vitro methods were used for our investigation into the antihypertensive effects of diosmetin.
Diosmetin significantly decreased the mean arterial pressure (MAP). The effects of diosmetin on the MAP and heart rate were more pronounced in hypertensive rats. To explore the involvement of the muscarinic receptors-linked NO pathway, Nω-nitro-L-arginine methyl ester (L-NAME) and atropine were pre-administered in vivo. The pretreatment with L-NAME did not significantly change the effects of diosmetin on the MAP by excluding the involvement of NO. Unlike L-NAME, the atropine pretreatment reduced the effects of diosmetin on the MAP, which demonstrated the role of the muscarinic receptors. In the in vitro study, diosmetin at lower concentrations produced endothelium-dependent and -independent (at higher concentrations) vasorelaxation, which was attenuated significantly by the presence of atropine and indomethacin but not L-NAME. Diosmetin was also tested for high K+-induced contractions. Diosmetin induced significant relaxation (similar to verapamil), which indicated its Ca2+ antagonistic effects. This was further confirmed by diosmetin shifting the CaCl CRCs toward the right due to its suppression of the maximum response. Diosmetin also suppressed phenylephrine peak formation, which indicated its antagonist effects on the release of Ca2+. Moreover, BaCl significantly inhibited the effects of diosmetin, followed by 4-AP and TEA, which suggested that the K+ channels had a role as well.
The obtained data showed the Ca2+ channel antagonism, potassium channel activation and antimuscarinic receptor-linked vasodilatory effects of diosmetin, which demonstrated its antihypertensive potential.
香叶木素是一种黄酮类化合物，存在于许多具有抗高血压治疗潜力的重要药用植物中。已证明香叶木素具有抗血小板、抗炎和抗氧化特性，这表明它可能是抗高血压治疗的潜在候选药物。
采用体内和体外方法研究香叶木素的抗高血压作用。
香叶木素显著降低平均动脉压（MAP）。香叶木素对MAP和心率的影响在高血压大鼠中更为明显。为了探究毒蕈碱受体相关的一氧化氮（NO）途径的参与情况，在体内预先给予Nω-硝基-L-精氨酸甲酯（L-NAME）和阿托品。通过排除NO的参与，L-NAME预处理并未显著改变香叶木素对MAP的影响。与L-NAME不同，阿托品预处理降低了香叶木素对MAP的影响，这证明了毒蕈碱受体的作用。在体外研究中，较低浓度的香叶木素产生内皮依赖性（较高浓度时为非内皮依赖性）血管舒张，阿托品和吲哚美辛的存在可显著减弱这种作用，但L-NAME无此作用。还测试了香叶木素对高钾诱导收缩的影响。香叶木素诱导显著的舒张（类似于维拉帕米），表明其具有钙拮抗作用。香叶木素通过抑制最大反应使氯化钙累积量-反应曲线（CRCs）向右移动，进一步证实了这一点。香叶木素还抑制去氧肾上腺素峰值的形成，表明其对钙释放具有拮抗作用。此外，氯化钡显著抑制香叶木素的作用，其次是4-氨基吡啶（4-AP）和四乙铵（TEA），这表明钾通道也发挥了作用。
所得数据表明香叶木素具有钙通道拮抗、钾通道激活和抗毒蕈碱受体相关的血管舒张作用，证明了其抗高血压潜力。
