Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, California, USA.
Vascular Biology Group, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
FASEB J. 2023 Sep;37(9):e23125. doi: 10.1096/fj.202301132R.
The evergreen plant rosemary (Salvia rosmarinus) has been employed medicinally for centuries as a memory aid, analgesic, spasmolytic, vasorelaxant and antihypertensive, with recent preclinical and clinical evidence rationalizing some applications. Voltage-gated potassium (Kv) channels in the KCNQ (Kv7) subfamily are highly influential in the nervous system, muscle and epithelia. KCNQ4 and KCNQ5 regulate vascular smooth muscle excitability and contractility and are implicated as antihypertensive drug targets. Here, we found that rosemary extract potentiates homomeric and heteromeric KCNQ4 and KCNQ5 activity, resulting in membrane hyperpolarization. Two rosemary diterpenes, carnosol and carnosic acid, underlie the effects and, like rosemary, are efficacious KCNQ-dependent vasorelaxants, quantified by myography in rat mesenteric arteries. Sex- and estrous cycle stage-dependence of the vasorelaxation matches sex- and estrous cycle stage-dependent KCNQ expression. The results uncover a molecular mechanism underlying rosemary vasorelaxant effects and identify new chemical spaces for KCNQ-dependent vasorelaxants.
迷迭香（Rosmarinus officinalis）作为一种记忆辅助剂、镇痛药、平滑肌松弛剂、血管舒张剂和降压药，已经在医学上应用了几个世纪，最近的临床前和临床证据为其一些应用提供了合理依据。电压门控钾（Kv）通道中的 KCNQ（Kv7）亚家族在神经系统、肌肉和上皮组织中具有重要作用。KCNQ4 和 KCNQ5 调节血管平滑肌的兴奋性和收缩性，被认为是降压药物的靶点。在这里，我们发现迷迭香提取物增强了同型和异型 KCNQ4 和 KCNQ5 的活性，导致膜超极化。两种迷迭香二萜，鼠尾草酸和迷迭香酸，是产生这种效果的基础物质，与迷迭香一样，它们是有效的 KCNQ 依赖性血管舒张剂，在大鼠肠系膜动脉的肌动描记术中进行了定量分析。血管舒张作用的性别和动情周期阶段依赖性与 KCNQ 表达的性别和动情周期阶段依赖性相匹配。研究结果揭示了迷迭香血管舒张作用的分子机制，并为 KCNQ 依赖性血管舒张剂开辟了新的化学空间。
