One new (1) and two known angular-type (2,3) furocoumarins, isoarchangelicin (1), archangelicin (2), and 2′-angeloyl-3′-isovaleryl vaginate (3), were isolated from the roots of Angelica atropurpurea. The structure of the new compound was established on the basis of one- and two-dimensional NMR spectra and other spectroscopic studies. The inhibitory activity of these three compounds and a deacylated form of archangelicin (4) on the nuclear factor of activated T cells (NFAT) signal transduction pathway was tested by NFAT-responsive luciferase reporter gene assay in cultured cells. Although 4 did not exhibit inhibitory activity on NFAT signaling, 1–3 exhibited dose-dependent inhibition with IC50 values of 16.5 (1), 9.0 (2), and 9.2 (3) μM.
(a) ShawJ.P., UtzP.J., DurandD.B., TooleJ.J., EmmelE.A., CrabtreeG.R. (1988) Identification of a putative regulator of early T cell activation genes. Science, 241, 202–205;(b) Emmel EA, Verweij CL, Durand DB, Higgins KM, Lacy E, Crabtree GR. (1989) Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science, 246, 1617–1620; (c) Henderson DJ, Naya I, Bundick RV, Smith GM, Schmidt JA. (1991) Comparison of the effects of FK-506, cyclosporin A and rapamycin on IL-2 production. Immunology, 73, 316–321.
2.
RaoA., LuoC., HoganP.G. (1997) Transcription factors of the NFAT family: regulation and function. Annual Review of Immunology, 15, 707–747.
3.
MatsudaS., KoyasuS. (2000) Mechanisms of action of cyclosporine. Immunopharmacology, 47, 119–125.
4.
Martínez-MartínezS., RedondoJ.M. (2004) Inhibitors of the calcineurin/NFAT pathway. Current Medicinal Chemistry, 11, 997–1007.
5.
(a) MorE., PatelT., GlabmanS., SheinerP., EmreS., GuyS., SchwartzM., MillerC. (1994) Comparison of short and long-term renal function in liver transplant patients receiving cyclosporin or FK 506. Transplant International, 7 Suppl. 1, S77–S80; (b) Wiesner RH. (1998) A long-term comparison of tacrolimus (FK506) versus cyclosporine in liver transplantation: a report of the United States FK506 Study Group. Transplantation, 66, 493–499.
6.
LiuC., HermannT.E. (1978) Characterization of ionomycin as a calcium ionophore. Journal of Biological Chemistry, 253, 5892–5894.
7.
(a) BerenbaumM. (1981) Patterns of furanocoumarin distribution and insect herbivory in the Umbelliferae: Plant chemistry and community structure. Ecology, 62, 1254–1266;(b) Márquez N, Sancho R, Ballero M, Bremner P, Appendino G, Fiebich BL, Heinrich M, Muñoz E. (2004) Imperatorin inhibits T-cell proliferation by targeting the transcription factor NFAT. Planta Medica, 70, 1016–1021.
8.
(a) ColombainM., GollV., MuyardF., GirardC., BévalotF., RichertL. (2001) A bioassay using the human hepatoblastoma cell line HepG2 for detecting phototoxicity of furocoumarins. Planta Medica, 67, 644–646; (b) Muller M, Byres M, Jaspars M, Kumarasamy Y, Middleton M, Nahar L, Shoeb M, Sarker SD. (2004) 2D NMR spectroscopic analyses of archangelicin from the seeds of Angelica archangelica. Acta Pharmaceutica, 54, 277–285; (c) Ikeshiro Y, Mase I, Tomita Y. (1992) Dihydropyranocoumarins from roots of Peucedanum japonicum. Phytochemistry, 31, 4303-4306.
9.
HärmäläP., KaltiaS., VuorelaH., HiltunenR. (1992) A furanocoumarin from Angelica archangelica. Planta Medica, 58, 287–289.
10.
OkuyamaT., TakataM., TakayasuJ., HasegawaT., TokudaH., NishinoA., NishinoH., IwashimaA. (1991) Anti-tumor-promotion by principles obtained from Angelica keiskei. Planta Medica, 57, 242–246.
11.
(a) RoosG., WaiblingerJ., ZschockeS., LiuJ.H., KlaiberI., KrausW., BauerR. (1997) Isolation, identification and screening for COX-1- and 5-LO-inhibition of coumarins from Angelica archangelica. Pharmaceutical and Pharmacological Letters, 7, 157–160;(b) Thastrup O, Knudsen JB, Lemmich J, Winther K. (1985) Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors. Biochemical Pharmacology, 34, 2137–2140; (c) Ojala T, Vuorela P, Kiviranta J, Vuorela H, Hiltunen R. (1999) A bioassay using Artemia salina for detecting phototoxicity of plant coumarins. Planta Medica, 65, 715–718.
