School of Pharmacy, University of Nottingham Malaysia, Semenyih, Malaysia.
School of Life Sciences, University of Nottingham, Nottingham, UK.
Phytother Res. 2022 Jul;36(7):2952-2963. doi: 10.1002/ptr.7489. Epub 2022 May 10.
This study investigated the vasorelaxant effects of schwarzinicine A, an alkaloid recently reported from Ficus schwarzii Koord. Regulation of calcium homeostasis in vascular smooth muscle cells (VSMC) is viewed as one of the main mechanisms for controlling blood pressure. L-type voltage-gated calcium channel (VGCC) blockers are commonly used for controlling hypertension. Recently, the transient receptor potential canonical (TRPC) channels were found in blood vessels of different animal species with evidence of their roles in the regulation of vascular contractility. In this study, we studied the mechanism of actions of schwarzinicine A focusing on its regulation of L-type VGCC and TRPC channels. Schwarzinicine A exhibited the highest vasorelaxant effect (123.1%) compared to other calcium channel blockers. It also overtly attenuated calcium-induced contractions of the rat isolated aortae in a calcium-free environment showing its mechanism to inhibit calcium influx. Fluorometric intracellular calcium recordings confirmed its inhibition of hTRPC3-, hTRPC4-, hTRPC5- and hTRPC6-mediated calcium influx into HEK cells with IC values of 3, 17, 19 and 7 μM, respectively. The evidence gathered in this study suggests that schwarzinicine A blocks multiple TRPC channels and L-type VGCC to exert a significant vascular relaxation response.
本研究调查了从榕属 Koord 中分离得到的生物碱——黑桑定 A 的血管舒张作用。调节血管平滑肌细胞（VSMC）中的钙离子稳态被视为控制血压的主要机制之一。L 型电压门控钙通道（VGCC）阻滞剂通常用于控制高血压。最近，在不同动物物种的血管中发现了瞬时受体电位经典（TRPC）通道，并证实了它们在调节血管收缩性方面的作用。在这项研究中，我们研究了黑桑定 A 的作用机制，重点关注其对 L 型 VGCC 和 TRPC 通道的调节。与其他钙通道阻滞剂相比，黑桑定 A 表现出最高的血管舒张作用（123.1%）。它还明显减弱了在无钙环境中大鼠分离的主动脉的钙诱导收缩，表明其抑制钙内流的机制。荧光细胞内钙离子记录证实了它对 hTRPC3、hTRPC4、hTRPC5 和 hTRPC6 介导的钙内流的抑制作用，IC 值分别为 3、17、19 和 7 μM。本研究的证据表明，黑桑定 A 通过阻断多种 TRPC 通道和 L 型 VGCC 发挥显著的血管舒张反应。
