title: Heartwood extract of Rhus verniciflua Stokes and its active constituent fisetin attenuate vasoconstriction through calcium-dependent mechanism in rat aorta.
abstract: Rhus verniciflua Stokes (RVS) exert cardiovascular protective activity by promoting blood circulation, but its active ingredients and underlying mechanism have yet to be identified. This study investigated the vascular effects of RVS, focusing on vasoconstriction and smooth muscle Ca(2+) signaling. RVS heartwood extract attenuated contraction of aortic rings induced by the vasoconstrictors serotonin and phenylephrine, and inhibited the Ca(2+) signaling evoked by serotonin in vascular smooth muscle cells. Subsequent activity-guided fractionation identified fisetin as an active constituent exerting a Ca(2+) inhibitory effect. Fisetin could inhibit major Ca(2+) mobilization pathways including extracellular Ca(2+) influx mediated by the L-type voltage-gated Ca(2+) channel, Ca(2+) release from the intracellular store and store-operated Ca(2+) entry. In accordance with Ca(2+) inhibitory effect, fisetin attenuated vasoconstriction by serotonin and phenylephrine. These results suggest that the anticontractile effect, which is presumably mediated by inhibition of Ca(2+) signaling, may contribute to the improvement of blood circulation by RVS.
authors.affiliation: a College of Pharmacy , Dongguk University , Goyang , Republic of Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Park
authors.affiliation: a College of Pharmacy , Dongguk University , Goyang , Republic of Korea.
authors.forename: Jun-Hyeong
authors.initials: JH
authors.lastname: Lee
authors.affiliation: b Lifetree Biotechnology Institute , Lifetree Biotech Co. Ltd. , Suwon , Republic of Korea.
authors.forename: Chun-Soo
authors.initials: CS
authors.lastname: Na
authors.affiliation: c College of Life Sciences and Biotechnology , Korea University , Seoul , Republic of Korea.
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.affiliation: d Laboratory of Pharmaceutical Health Sciences , School of Pharmacy, Aichi Gakuin University , Nagoya , Japan.
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: d Laboratory of Pharmaceutical Health Sciences , School of Pharmacy, Aichi Gakuin University , Nagoya , Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
authors.affiliation: a College of Pharmacy , Dongguk University , Goyang , Republic of Korea.
authors.forename: Moo-Yeol
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D029045:Rhus / Q000737:chemistry*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D044948:Flavonols; D010936:Plant Extracts; C017875:fisetin; D002118:Calcium
keywords: Rhus verniciflua Stokes; calcium signaling; fisetin; vascular smooth muscle cells; vasoconstriction