Water extract of Zanthoxylum piperitum induces vascular relaxation via endothelium-dependent NO-cGMP signaling

• Published in: Journal of ethnopharmacology Vol. 129; no. 2; pp. 197 - 202
• Main Authors: Li, Xiang, Kim, Hye Yoom, Cui, Hao Zhen, Cho, Kyung Woo, Kang, Dae Gill, Lee, Ho Sub
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 27.05.2010; Amsterdam; New York: Elsevier; Elsevier
• Subjects: Androstadienes - pharmacology; animal models; Animals; aorta; biochemical pathways; Biological and medical sciences; Boron Compounds - pharmacology; Calcium - metabolism; calcium channels; Calcium Channels - metabolism; cyclic GMP; Cyclic GMP - metabolism; Dose-Response Relationship, Drug; endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; fractionation; Gadolinium - pharmacology; General pharmacology; in vitro studies; ion transport; Male; mechanism of action; Medical sciences; medicinal plants; medicinal properties; NG-Nitroarginine Methyl Ester - pharmacology; nitric oxide; Nitric Oxide - metabolism; nitric oxide synthase; Nitric Oxide Synthase Type III - metabolism; NO-cGMP signaling; Oxadiazoles - pharmacology; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; plant extracts; Plant Extracts - pharmacology; Proto-Oncogene Proteins c-akt - metabolism; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; signal transduction; Signal Transduction - drug effects; smooth muscle; Store-operated Ca 2+ entry; Thapsigargin - pharmacology; tissue culture; Vasoconstriction - drug effects; vasodilation; Vasodilator Agents - pharmacology; Vasorelaxation; Zanthoxylum; Zanthoxylum - chemistry; Zanthoxylum piperitum; NO; L-NAME; Zanthoxylum piperitum; IBMX; cGMP; SERCA; NO-cGMP signaling; Vasorelaxation; sGC; 2-APB; Gd 3; NOS; PE; SOCE; K ATP; Store-operated Ca 2+ entry; ODQ; Pharmacognosy; Rutaceae; Store-operated Ca; 3',5'-GMP; Extract; Vasodilation; Endothelium; Medicinal plant; entry; Vasomotricity; Dicotyledones; Angiospermae; Plant origin; Spermatophyta
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2010.03.003

Effects of AZP on the vasorelaxation in the presence and absence of endothelium. The aim of the present study was to define the effects of extracts of leaves of Zanthoxylum piperitum (ZP) on the vascular tension and its mechanisms responsible in rat thoracic aortic rings. Methanol extract of ZP and aqueous fraction of the methanol extract (AZP) were examined for their vascular relaxant effects in isolated phenylephrine-precontracted aortic rings. Methanol extract of ZP and aqueous fraction of the methanol extract (AZP) induced relaxation of the phenylephrine-precontracted aortic rings in a concentration-dependent manner. Endothelium-denudation abolished the AZP-induced vasorelaxation. Pretreatment of the endothelium-intact aortic rings with N G-nitro- l-arginine methylester (L-NAME) and 1H-[1,2,4]-oxadiazolo-[4,3-α]-quinoxalin-1-one (ODQ) inhibited the AZP-induced vasorelaxation. Inhibition of Ca 2+ entry via L-type Ca 2+ channels failed to block the AZP-induced vasorelaxation. Extracellular Ca 2+ depletion slightly but significantly attenuated the AZP-induced vasorelaxation. Thapsigargin significantly attenuated the AZP-induced vasorelaxation. Further, Gd 3+ and 2-aminoethyl diphenylborinate (2-APB), inhibitors of store-operated Ca 2+ entry (SOCE), markedly attenuated the AZP-induced vasorelaxation. Also, wortmannin, an inhibitor of Akt, an upstream signaling molecule of eNOS, attenuated the AZP-induced vasorelaxation. AZP increased cGMP levels of the aortic rings in a concentration-dependent manner and the effect was blocked by L-NAME, ODQ, thapsigargin, Gd 3+, 2-APB, and wortmannin. K + channel inhibition with glibenclamide and tetraethylammonium, cyclooxygenase inhibition with indomethacin, and adrenergic and muscarinic receptors blockade had no effects on the AZP-induced vasorelaxation. Taken together, the present study suggests that AZP relaxes vascular smooth muscle via endothelium-dependent activation of NO-cGMP signaling through the Akt- and SOCE-eNOS pathways.