TY - JOUR

T1 - KCNQ5 activation by tannins mediates vasorelaxant effects of barks used in Native American botanical medicine

AU - Manville, Rían W

AU - Redford, Kaitlyn E

AU - van der Horst, Jennifer

AU - Hogenkamp, Derk J

AU - Jepps, Thomas A

AU - Abbott, Geoffrey W

N1 - Publisher Copyright: © 2022 Federation of American Societies for Experimental Biology.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Bark

KW - Hypotensive

KW - KCNQ

KW - Kv7

KW - Tannin

KW - Vasorelaxant

U2 - 10.1096/fj.202200724R

DO - 10.1096/fj.202200724R

M3 - Journal article

C2 - 35997997

AN - SCOPUS:85136898464

VL - 36

JO - F A S E B Journal

JF - F A S E B Journal

SN - 0892-6638

IS - 9

M1 - e22457

ER -