Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta

Sunny Sun Kin Chan, Angela On Ki Choi, Robert Leslie Jones, Ge Lin

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Butylidenephthalide (BDPH) is one of the most potent vasorelaxants isolated from Ligusticum chuanxiong Hort. The objective of the current study is to investigate the underlying vasorelaxation mechanisms in rat aorta. In 9,11-dideoxy-9α,11α-methanoepoxyprostaglandin F (U46619) precontracted preparations, endothelium removal, the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) partially inhibited the BDPH relaxation response to a similar extent. The cyclooxygenase inhibitor indomethacin, β-adrenoceptor antagonist propranolol, adenylate cyclase inhibitors 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and 2′,5′-dideoxyadenosine, and K+ channel blocker tetraethylammonium had no effect. BDPH produced full relaxation against contractions induced by KCl and U46619 in the presence of the l-type voltage-operated Ca2+ channel (Cav 1.2) blocker nifedipine. In a receptor-operated Ca2+ channel protocol where contraction was mediated by Ca2+ re-addition in the presence of U46619 and nifedipine, BDPH produced relaxation. In the absence of extracellular Ca2+, BDPH inhibited contractions induced by phorbol-12,13-dibutyrate and U46619. Our results suggest that BDPH-mediated vasorelaxation comprises both endothelium-dependent (NO) and independent components. It is suggested that BDPH acting through an inhibitory mechanism downstream to l-type voltage-operated and prostanoid TP receptor-operated Ca2+ channels operating late in the contractile pathway.

Original languageEnglish (US)
Pages (from-to)111-117
Number of pages7
JournalEuropean Journal of Pharmacology
Volume537
Issue number1-3
DOIs
StatePublished - May 10 2006

Bibliographical note

Funding Information:
The current study was financially supported by the Innovation and Technology Commission, the Hong Kong SAR government and Kinetana Hong Kong Herbal Pharmaceuticals Limited (UIM/034).

Keywords

  • Butylidenephthalide
  • Calcium
  • Endothelium
  • Ligusticum chuanxiong
  • Smooth muscle relaxation

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