Lysimachia clethroides extract promote vascular relaxation via endothelium-dependent mechanism.
Lysimachia clethroides is widely used in traditional herbal medicine for many purposes, especially for blood vessel-related diseases in Korea and East Asia. Experiments were undertaken to determine whether hydro-alcoholic extract obtained from L. clethroides (LCE) has vasorelaxant activity in the rat aorta rings and, if so, to elucidate the underlying mechanism. Rat aorta rings were suspended in organ chambers for the measurement of changes in isometric tension in the presence or absence of several inhibitors. LCE induced endothelium-dependent vasodilation (ED50 = 6.1 mug/mL) and that was abolished by nitric oxide synthase inhibitor, N-nitro-L-arginine, and guanylyl cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one, PI3-kinase inhibitor, wortmannin, and cell permeable superoxide dismutase. In addition, LCE decreased vessels contraction by phenylephrine. Prostaglandin synthesis inhibitor, indometacin, and inhibitors of endothelium-derived hyperpolarizing factor, charybdotoxin plus apamin, did not affect vasodilatory effect of LCE. In cultured endothelial cells, LCE-induced phosphorylation of serine 1177-endothelial nitric oxide synthase and serine 473-Akt. LCE inhibited strongly nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in smooth muscle cells and angiotensin II-induced contraction of rat aorta. Finally, increased oxidative stress in rat aorta-induced by angiotensin II is ameliorated by LCE. Taken together, LCE induces an endothelium-dependent vasodilation and might be involved, at least in part, the activation of the nitric oxide-cyclic guanosine monophosphate pathway. In addition, LCE decreases oxidative stress in aorta by inhibition of NADPH oxidase activity. The present findings indicate that LCE could be a candidate of herbal medicine for cardiovascular diseases associated with disturbed NO production and endothelial dysfunction.
Lee
Jung-Ok
JO
Research and Development Center, Hanwha Pharma, Co. Ltd, Chuncheon, Republic of Korea.
Chang
Kiyuk
K
Kim
Chul Young
CY
Jung
Sang Hoon
SH
Lee
Seung-Woo
SW
Oak
Min-Ho
MH
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D055670:Medicine, Korean Traditional; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D029623:Primulaceae / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019255:NADPH Oxidases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt