Impairment of vascular function of rat thoracic aorta in an endothelium-dependent manner by shikonin/alkannin and derivatives isolated from roots of Macrotomia euchroma.
The effects of a naphthoquinone analogue, shikonin/alkannin (SA) and derivatives (acetylshikonin and beta,beta-dimethylacrylshikonin), on vascular reactivity were studied with isolated rat aortic rings. At lower concentrations, SA and its derivatives concentration-dependently inhibit the agonist-induced (acetylcholine and histamine) relaxation in PE precontracted aorta in an endothelium-dependent manner with IC (50) values ranging from 0.2 to 1.5 microM. In addition to the effect on agonist-induced vasorelaxation, the Ca (2+) ionophore A23187-induced vasorelaxation was also inhibited or reversed by SA. However, SA had no effect on sodium nitroprusside-induced (guanylate cyclase activator) vasorelaxation. These data suggested that SA and its derivatives might be acting as inhibitors of nitric oxide synthesis in endothelium. At a concentration greater than 10 microM, SA induced contraction of intact but not denuded aorta which could be inhibited by prior treatment with indomethacin, a cyclooxygenase inhibitor. In summary, the results from this study showed that SA and its derivatives inhibited agonist-induced relaxation at lower concentrations and induced vasocontraction at higher concentrations. All the effects seen with SA were endothelium-dependent, however, through different mechanisms. Abbreviations. SA:shikonin/alkannin PE:phenylephrine Ach:acetylcholine SNP:sodium nitroprusside eNOS:endothelial nitric oxide synthase L-NAME: Nw-nitro- L-arginine methyl ester
Hu
Chien-Ming
CM
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Cheng
Yu-Wen
YW
Cheng
Hui-Wen
HW
Kang
Jaw-Jou
JJ
D000109:Acetylcholine; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D028082:Boraginaceae; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D006632:Histamine; D020128:Inhibitory Concentration 50; D009119:Muscle Contraction / Q000187:drug effects; D009285:Naphthoquinones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018517:Plant Roots; D051381:Rats; D017208:Rats, Wistar
D009285:Naphthoquinones; D010936:Plant Extracts; C018204:alkannin; C016101:shikonin; D006632:Histamine; D000109:Acetylcholine