Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, California, USA.
Department of Biomedical Sciences, Vascular Biology Group, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
FASEB J. 2022 Sep;36(9):e22457. doi: 10.1096/fj.202200724R.
Tree and shrub barks have been used as folk medicine by numerous cultures across the globe for millennia, for a variety of indications, including as vasorelaxants and antispasmodics. Here, using electrophysiology and myography, we discovered that the KCNQ5 voltage-gated potassium channel mediates vascular smooth muscle relaxant effects of barks used in Native American folk medicine. Bark extracts (1%) from Birch, Cramp Bark, Slippery Elm, White Oak, Red Willow, White Willow, and Wild Cherry each strongly activated KCNQ5 expressed in Xenopus oocytes. Testing of a subset including both the most and the least efficacious extracts revealed that Red Willow, White Willow, and White Oak KCNQ-dependently relaxed rat mesenteric arteries; in contrast, Black Haw bark neither activated KCNQ5 nor induced vasorelaxation. Two compounds common to the active barks (gallic acid and tannic acid) had similarly potent and efficacious effects on both KCNQ5 activation and vascular relaxation, and this together with KCNQ5 modulation by other tannins provides a molecular basis for smooth muscle relaxation effects of Native American folk medicine bark extracts.
数千年来，全球许多文化都将树木和灌木树皮用作民间药物，用于多种适应症，包括血管舒张剂和抗痉挛药。在这里，我们使用电生理学和肌电图技术发现，KCNQ5 电压门控钾通道介导了在美洲原住民民间医学中使用的树皮的血管平滑肌松弛作用。桦树皮、莶草、榆树皮、白橡木、红柳树、白柳树和野樱桃的树皮提取物（1％）均强烈激活了在非洲爪蟾卵母细胞中表达的 KCNQ5。对包括最有效和最无效的提取物在内的亚组进行测试表明，红柳树、白柳树和白橡木 KCNQ 依赖性地松弛大鼠肠系膜动脉；相比之下，黑霍克树皮既不激活 KCNQ5 也不引起血管松弛。两种常见于有效树皮的化合物（没食子酸和单宁酸）对 KCNQ5 的激活和血管松弛具有相似的强大和有效作用，并且这与其他单宁对 KCNQ5 的调节一起为美洲原住民民间医学树皮提取物的平滑肌松弛作用提供了分子基础。
