Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):952-957. doi: 10.1016/j.bbrc.2020.09.102. Epub 2020 Sep 30.
Quercetin is a natural flavonoid which has been reported to be analgesic in different animal models of pain. However, the mechanism underlying the pain-relieving effects is still unclear. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play critical roles in controlling pacemaker activity in cardiac and nervous systems, making the channel a new target for therapeutic exploration. In this study, we explored a series of flavonoids for their modulation on HCN channels. Among all tested flavonoids, quercetin was the most potent inhibitor for HCN channels with an IC value of 27.32 ± 1.19 μM for HCN2. Furthermore, quercetin prominently left shifted the voltage-dependent activation curves of HCN channels and decelerated deactivation process. The results presented herein firstly characterize quercetin as a novel and potent inhibitor for HCN channels, which represents a novel structure for future drug design of HCN channel inhibitors.
槲皮素是一种天然类黄酮，据报道在不同的疼痛动物模型中具有镇痛作用。然而，其镇痛作用的机制尚不清楚。超极化激活环核苷酸门控（HCN）通道在控制心脏和神经系统的起搏活动中起着关键作用，使该通道成为治疗探索的新靶点。在这项研究中，我们探索了一系列类黄酮对 HCN 通道的调节作用。在所测试的所有类黄酮中，槲皮素对 HCN 通道的抑制作用最强，对 HCN2 的 IC 值为 27.32±1.19 μM。此外，槲皮素明显左移了 HCN 通道的电压依赖性激活曲线，并减缓了失活过程。本文的研究结果首次将槲皮素表征为 HCN 通道的一种新型有效抑制剂，为未来 HCN 通道抑制剂的药物设计提供了一种新的结构。
