Xanthine Oxidase Inhibitors from the Flowers of Chrysanthemum sinense

Abstract

From the MeOH extract of the flowers of Chrysanthemum sinense, a new flavone glucoside, acacetin 7-O-(3-O-acetyl-β-D-glucopyranoside) (1), has been isolated together with 27 known compounds including flavonoids, caffeoylquinic acid derivatives, phenolics, and a monoterpenoid glucoside. Their structures were elucidated on the basis of spectroscopic data. Compounds 1 - 15, 20 - 24, and 27 displayed significant xanthine oxidase inhibitory activity in a concentration-dependent manner, and compounds 2 - 11 and 22 showed more potent inhibitory activity, with IC₅₀ values ranging from 0.13 to 2.31 μM, than that of a positive control allopurinol (IC₅₀ = 2.50 μM). The kinetic study indicated that 1 - 15 and 20 - 24 displayed competitive-type inhibition like that of allopurinol, while 27 displayed a mixed-type inhibition.

Key words

Chrysanthemum sinense - Asteraceae - acacetin 7-O-(3-O-acetyl-β-D-glucopyranoside) - flavonoids - caffeoylquinic acid - phenolics - Xanthine oxidase inhibition

References

• 1 Oettl K, Reibnegger G. Pteridines as inhibitors of xanthine oxidase: structural requirements.  Biochim Biophys Acta. 1999;  1430 387-95
• 2 Ishibuchi S, Morimoto H, Oe T, Ikebe T, Inoue H, Fukunari A. et al . Synthesis and structure-activity relationships of 1-phenylpyrazoles as xanthine oxidase inhibitors.  Bioorg Med Chem Lett. 2001;  11 879-82
• 3 Cos P, Ying L, Calomme M, Hu J P, Cimanga K, Van Poel B. et al . Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers.  J Nat Prod. 1998;  61 71-6
• 4 Do T L. Vietnamese Medicinal Plants. Hanoi; Medicine Publisher 2001: p 604
• 5 Nguyen M TT, Awale S, Tezuka Y, Tran L Q, Watanabe H, Kadota S. Xanthine oxidase inhibitory activity of Vietnamese medicinal plants.  Biol Pharm Bull. 2004;  27 1414-21
• 6 Harborne J B, Mabry T J. The flavonoids: advances in research, 1st Edition. Cambridge; Cambridge University Press 1982: pp 52-130
• 7 Wollenweber E, Vetschera K M, Ivancheva S, Kuzmanov B. Flavonoid aglycones from the leaf surfaces of some Achillea species.  Phytochemistry. 1987;  26 181-2
• 8 Marco J A, Barbera O, Rodriguez S, Domingo C, Adell J. Flavonoids and other phenolics from Artemisia hispanica .  Phytochemistry. 1988;  27 3155-9
• 9 Martinez-Vazquez M, Garcia H MV, Toscano R A, Perez G E. Methylated flavones from Conoclidium greggii .  J Nat Prod. 1993;  56 1410-3
• 10 Mues R, Timmermann B N, Ohno N, Mabry T J. 6-Methoxyflavonoids from Brickellia californica .  Phytochemistry. 1979;  18 1379-83
• 11 Sanchez A R, Vazquez P. Quinic acid ester from Isertia haenkeana .  Phytochemistry. 1991;  30 311-3
• 12 Pauli G , Poetsch F, Nahrstedt A. Structure assignment of natural quinic acid derivatives using proton nuclear magnetic resonance techniques.  Phytochem Anal. 1998;  9 177-85
• 13 Saleh N AM, Elnegoumy S I, Abouzaid M M. Flavonoids of Artemisia judaica, A. monosperma and A. herba-alba .  Phytochemistry. 1987;  26 3059-64
• 14 Gongora L, Giner R M, Manez S, Recio M C, Rios J L. Phagnalon rupestre as a source of compounds active on contact hypersensitivity.  Planta Med. 2002;  68 561-4
• 15 Basnet P, Matsushige K, Hase K, Kadota S, Namba T. Four di-O-caffeoyl quinic acid derivatives from propolis. Potent hepatoprotective activity in experimental liver injury model.  Biol Pharm Bull. 1996;  19 1479-84
• 16 Guz N R, Stermitz F R. Synthesis and structures of regioisomeric hydnocarpin-type flavonolignans.  J Nat Prod. 2000;  63 1140-5
• 17 Pauli G F, Kuczkowiak U, Nahrstedt A. Solvent effects in the structure dereplication of caffeoyl quinic acids.  Magn Reson Chem. 1999;  37 827-36
• 18 Silva F AM, Borges F, Guimaraes C, Lima J LMC, Matos C, Reis S. Phenolic acids and derivatives: studies on the relationship among structure, radical scavenging activity, and physicochemical parameters.  J Agric Food Chem. 2000;  48 2122-6
• 19 Mpondo E M, Garcia J, Chulia A J, Mariotte A M. A new C₁₃ glycoside from Gentiana pneumonanthe .  Planta Med. 1989;  55 492
• 20 Hara S, Okabe H, Mihashi K. Gas-liquid chromatography separation of aldose enantiomers as trimethylsilyl ethers of methyl 2-(polyhydroxyalkyl)-thiazolidine-4(R)-carboxylates.  Chem Pharm Bull. 1987;  35 501-6
• 21 Noro T, Oda Y, Miyase T, Ueno A, Fukushima S. Inhibitors of xanthine oxidase from the flowers and buds of Daphne genkwa .  Chem Pharm Bull. 1983;  31 3984-7
• 22 Borges F, Fernandes E, Roleira F. Progress towards the discovery of xanthine oxidase inhibitors.  Curr Med Chem. 2002;  9 195-217