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KCNQ5 activation by tannins mediates vasorelaxant effects of barks used in Native American botanical medicine.
Manville RW
,
Redford KE
,
van der Horst J
,
Hogenkamp DJ
,
Jepps TA
,
Abbott GW
.
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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.
801199 European Union's Horizon 2020 Research and Innovation Program, GM130377 HHS | NIH | National Institute of General Medical Sciences (NIGMS), T32NS045540 HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS), R323-2018-3674 Lundbeckfonden (Lundbeck Foundation), Samueli Scholarship, R35 GM130377 NIGMS NIH HHS , T32 NS045540 NINDS NIH HHS
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