Endothelium-dependent vasorelaxant and antiproliferative effects of apigenin

• Published in: General pharmacology 2000-12, Vol.35 (6), p.341-347
• Main Authors: Zhang, Yong-He, Park, Yang-Su, Kim, Tack-Joong, Fang, Lian-Hua, Ahn, Hee-Yul, Hong, JinTae, Kim, Youngsoo, Lee, Chong-Kil, Yun, Yeo-Pyo
• Format: Article
• Language: English
• Subjects: Animals; Aorta, Thoracic - cytology; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Apigenin; Biological and medical sciences; Cell Division - drug effects; Cells, Cultured; cGMP; Cyclic GMP - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Flavonoids - pharmacology; General pharmacology; Isometric Contraction - drug effects; Male; Medical sciences; Methylene Blue - pharmacology; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phorbol 12,13-Dibutyrate - pharmacology; Proliferation; Rat aorta; Rats; Rats, Sprague-Dawley; Thymidine - metabolism; Vasorelaxation
• ISSN: 0306-3623; 1879-0011
• DOI: 10.1016/S0306-3623(02)00113-1

This study was designed to determine whether the relaxant effect of apigenin was endothelium dependent and to examine the possible antiproliferative effect of apigenin. Apigenin relaxed the phenylephrine-precontracted endothelium-intact aortic rings with IC 50 value of 3.7±0.5 μM and removal of a functional endothelium significantly attenuated this relaxation (IC 50=8.2±0.9 μM). However, apigenin did not affect the 0.1 μM phorbol 12,13-dibutyrate-induced contraction (IC 50=34.6±1.2 μM) within the concentration range that relaxed the phenylephrine-contracted arteries, suggesting that apigenin did not influence protein kinase C-mediated contractile mechanisms in rat aorta. Pretreatment of apigenin significantly potentiated the relaxant effect of acetylcholine on phenylephrine-induced contraction. Pretreatment with N G-nitro- l-arginine methyl ester ( l-NAME) or methylene blue reduced the relaxant effect of apigenin. Apigenin (10 μM) increased the guanosine 3′,5′-cyclic monophosphate (cGMP) content of endothelium-intact tissues. Pretreatment with l-NAME (100 μM) or removal of endothelium significantly suppressed the effect of apigenin on cGMP production. In addition, apigenin significantly inhibited [ 3H]thymidine incorporation into DNA of primary cultured rat aortic smooth muscle cell in a dose-dependent manner. These findings suggest that besides influx and release of Ca 2+, nitric oxide (NO) and cGMP may account for the apigenin-induced endothelium-dependent relaxation and hypotensive activity. Both vasorelaxant and antiproliferative activities may contribute to a benefit of apigenin in the vascular system.