Japonicones E–L, Dimeric Sesquiterpene Lactones from Inula japonica Thunb.

Abstract

Eight new dimeric sesquiterpene lactones (japonicones E–L, 1–8), including a novel sesquiterpene dimer bearing a rare hydroperoxide group (japonicone E, 1), were isolated from the aerial part of Inula japonica Thunb. Their structures were determined mainly by the use of 1D and 2D NMR spectroscopic techniques including HSQC, ¹H-¹H COSY, HMBC, and NOESY. All the isolates were tested for inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Among the compounds tested, japonicone F (2) showed the strongest activity with the IC₅₀ value of 4.1 µg/mL.

Key words

japonicones E–L - sesquiterpene dimmer - Inula japonica Thunb. - Asteraceae - NO production

References

• 1 Lin R, Yu D J, Wu Z Y. Flora of China. Beijing; Science Press 1989: 263-265
• 2 Zhao Y M, Zhang M L, Shi Q W, Kiyota H. Chemical constituents of plants from the genus Inula.  Chem Biodivers. 2006;  3 371-384
• 3 Shan J J, Yang M, Ren J W. Anti-diabetic and hypolipidemic effects of aqueous-extract from the flower of Inula japonica in alloxan-induced diabetic mice.  Biol Pharm Bull. 2006;  29 455-459
• 4 Wang C M, Jia Z J, Zheng R L. The effect of 17 sesquiterpenes on cell viability and telomerase activity in the human ovarian cancer cell line HO-8910.  Planta Med. 2007;  73 180-184
• 5 Yang C, Wang C M, Jia Z J. Sesquiterpenes and other constituents from the aerial parts of Inula japonica.  Planta Med. 2003;  69 662-666
• 6 Jeske F, Huneck S, Jakupovic J. Secoeudesmanolides from Inula japonica.  Phytochemistry. 1993;  34 1647-1649
• 7 Qin J J, Jin H Z, Fu J J, Hu X J, Wang Y, Yan S K, Zhang W D. Japonicones A–D, bioactive dimeric sesquiterpenes from Inula japonica Thunb.  Bioorg Med Chem Lett. 2009;  19 710-713
• 8 Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability.  J Immunol Methods. 1986;  89 271-277
• 9 Jin H Z, Lee D, Lee J H, Hong Y S, Kim Y H, Lee J J. New dimeric sesquiterpenes from Inula britannica inhibit the NF-κB activation, NO and TNF-α production.  Planta Med. 2006;  72 40-45
• 10 Zdero G, Bohlmann F, Mueller M. Sesquiterpene lactones and other constituents from Eriocephalus species.  Phytochemistry. 1987;  26 2763-2775
• 11 Bai N S, Lai C S, He K, Zhou Z, Zhang L, Quan Z, Zhu N, Zheng Q Y, Pan M H, Ho C T. Sesquiterpene lactones from Inula britannica and their cytotoxic and apoptotic effects on human cancer cell lines.  J Nat Prod. 2006;  69 531-535
• 12 Su B N, Takaishi Y, Yabuuchi T, Kusumi T, Tori M, Takaoka S. The structures and absolute configuration of macrophyllic acids A–E, five new rearranged eudesmane sesquiterpene acids from the bark of Inula macrophylla.  Tetrahedron Lett. 2000;  41 2395-2400