Download PDF
Planta Med 2012; 78(10): 995-1001
DOI: 10.1055/s-0031-1298580
Natural Product Chemistry
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Geranyl Flavonoid Derivatives from the Fresh Leaves of Artocarpus communis and Their Anti-inflammatory Activity

Chin-Lin Hsu
1   School of Nutrition, Chung Shan Medical University and Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan
,
Fang-Rong Chang
2   Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
,
Pei-Yu Tseng
1   School of Nutrition, Chung Shan Medical University and Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan
,
Yi-Fen Chen
1   School of Nutrition, Chung Shan Medical University and Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan
,
Mohamed El-Shazly
2   Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
3   Department of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
,
Ying-Chi Du
2   Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
,
Song-Chwan Fang
4   Department of Food Nutrition, Chung Hwa University of Medical Technology, Tainan, Taiwan
› Author Affiliations
Further Information

Publication History

received 01 August 2011
revised 02 April 2012

accepted 24 April 2012

Publication Date:
22 May 2012 (online)

Also available at
    Permissions and Reprints

Abstract

Breadfruit (Artocarpus communis) is a widely distributed crop in tropical and subtropical regions of the world. It is used in Southeast Asia and India to treat several inflammatory disorders. The aim of this study was to investigate the presence of anti-inflammatory flavonoids in A. communis leaves. Three new geranyl flavonoids, arcommunol C (1), arcommunol D (3), and 5′-geranyl-3,4,2′,4′-tetrahydroxychalcone (5), together with four known compounds, prostratol (2), arcommunol E (4), 3′-geranyl-3,4,2′,4′-tetrahydroxydihydrochalcone (6), and 3′-geranyl-3,4,2′,4′-tetrahydroxychalcone (7), were isolated from the leaves of A. communis. Compound 4 was isolated for the first time from natural sources. The anti-inflammatory activity of the isolated compounds (1–7) was evaluated by determining their inhibitory activity on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Compounds 2, 3, and 4 suppressed the LPS-induced production of nitric oxide (NO) in RAW 264.7 cells with IC50 values of 8.13 ± 0.17, 18.45 ± 2.15, and 22.74 ± 1.74 µM, respectively. Furthermore, 2 decreased lipopolysaccharide (LPS)-mediated induction of protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. It was also found that 2 suppressed LPS-induced phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) signaling.

Key words

Artocarpus communis (Moraceae) - geranyl flavonoids - tetrahydroxychalcone - anti-inflammatory - lipopolysaccharide activated RAW 264.7 murine macrophage cells
 

  • References

  • 1 Tamir S, Tannenbaum SR. The role of nitric oxide (NO) in the carcinogenic process. Biochim Biophys Acta 1996; 1288: F31-F36
    PubMedGoogle Scholar
  • 2 Jeong GS, Lee DS, Kim YC. Cudratricusxanthone A from Cudrania tricuspidata suppresses pro-inflammatory mediators through expression of anti-inflammatory heme oxygenase-1 in RAW 264.7 macrophages. Int Immunopharmacol 2009; 9: 241-246
    CrossrefPubMedGoogle Scholar
  • 3 Kanwar JR, Kanwar RK, Burrow H, Baratchi S. Recent advances on the roles of NO in cancer and chronic inflammatory disorders. Curr Med Chem 2009; 16: 2373-2394
    CrossrefPubMedGoogle Scholar
  • 4 Tilg H, Wilmer A, Vogel W, Herold M, Nölchen B, Judmaier G, Huber C. Serum levels of cytokines in chronic liver diseases. Gastroenterology 1992; 103: 264-274
    PubMedGoogle Scholar
  • 5 Isomäki P, Punnonen J. Pro- and anti-inflammatory cytokines in rheumatoid arthritis. Ann Med 1997; 29: 499-507
    CrossrefPubMedGoogle Scholar
  • 6 Coker RK, Laurent GJ. Pulmonary fibrosis: cytokines in the balance. Eur Respir J 1998; 11: 1218-1221
    CrossrefPubMedGoogle Scholar
  • 7 Jagtap UB, Bapat VA. Artocarpus: a review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 2010; 129: 142-146
    CrossrefPubMedGoogle Scholar
  • 8 Fukai T, Satoh K, Nomura T, Sakagami H. Antinephritis and radical scavenging activity of prenylflavonoids. Fitoterapia 2003; 74: 720-724
    CrossrefPubMedGoogle Scholar
  • 9 Liou SS, Shieh WL, Cheng TH, Won SJ, Lin CN. γ-Pyrone compounds as potential anticancer drugs. J Pharm Pharmacol 1993; 45: 791-794
    CrossrefPubMedGoogle Scholar
  • 10 Shimizu K, Kondo R, Sakai K, Buabarn S, Dilokkunanant U. A geranylated chalcone with 5α-reductase inhibitory properties from Artocarpus incisus . Phytochemistry 2000; 54: 737-739
    CrossrefPubMedGoogle Scholar
  • 11 Jayasinghe L, Balasooriya BA, Padmini WC, Hara N, Fujimoto Y. Geranyl chalcone derivatives with antifungal and radical scavenging properties from the leaves of Artocarpus nobilis . Phytochemistry 2004; 65: 1287-1290
    CrossrefPubMedGoogle Scholar
  • 12 Wei BL, Weng JR, Chiu PH, Hung CF, Wang JP, Lin CN. Anti-inflammatory flavonoids from Artocarpus heterophyllus and Artocarpus communis . J Agric Food Chem 2005; 53: 3867-3871
    CrossrefPubMedGoogle Scholar
  • 13 Weng JR, Chan SC, Lu YH, Lin HC, Ko HH, Lin CN. Antiplatelet prenylflavonoids from Artocarpus communis . Phytochemistry 2006; 67: 824-829
    CrossrefPubMedGoogle Scholar
  • 14 Cheon BS, Kim YH, Son KS, Chang HW, Kang SS, Kim HP. Effects of prenylated flavonoids and biflavonoids on lipopolysaccharide induced nitric oxide production from the mouse macrophage cell line RAW 264.7. Planta Med 2000; 66: 596-600
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Han AR, Kang YJ, Windono T, Lee SK, Seo EK. Prenylated flavonoids from the heartwood of Artocarpus communis with inhibitory activity on lipopolysaccharide-induced nitric oxide production. J Nat Prod 2006; 69: 719-721
    CrossrefPubMedGoogle Scholar
  • 16 Lin JA, Fang SC, Wu CH, Huang SM, Yen GC. Anti-inflammatory effect of the 5, 7, 4′-trihydroxy-6-geranylflavanone isolated from the fruit of Artocarpus communis in S100B-induced human monocytes. J Agric Food Chem 2011; 59: 105-111
    CrossrefPubMedGoogle Scholar
  • 17 Hsu CL, Shyu MH, Lin JA, Yen GC, Fang SC. Cytotoxic effects of geranyl flavonoid derivatives from the fruit of Artocarpus communis in SK-Hep-1 human hepatocellular carcinoma cells. Food Chem 2011; 127: 127-134
    CrossrefPubMedGoogle Scholar
  • 18 Fang SC, Hsu CL, Yu YS, Yen GC. Cytotoxic effects of new geranyl chalcone derivatives isolated from the leaves of Artocarpus communis in SW 872 human liposarcoma cells. J Agric Food Chem 2008; 56: 8859-8868
    CrossrefPubMedGoogle Scholar
  • 19 Lim TK. Edible medicinal and non-medicinal plants, Volume 3, fruits. Heidelberg: Springer Science + Business Media; 2012: 287-300
    CrossrefGoogle Scholar
  • 20 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63
    CrossrefPubMedGoogle Scholar
  • 21 Tao JY, Zhao L, Huang ZJ, Zhang XY, Zhang SL, Zhang QG, Xiao F, Zhang BH, Feng QL, Zhang GH. Anti-inflammatory effects of ethanol extract from Kummerowia striata (Thunb.) Schindl on LPS-stimulated RAW 264.7 cell. Inflammation 2008; 31: 154-166
    CrossrefPubMedGoogle Scholar
  • 22 Dirsch VM, Stuppner H, Vollmar AM. The griess assay: suitable for a bio-guided fractionation of anti-inflammatory plant extracts. Planta Med 1998; 64: 423-426
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Radkar V, Lau-Cam L, Hardej D, Billack B. The role of surface receptor stimulation on the cytotoxicity of resveratrol to macrophages. Food Chem Toxicol 2008; 46: 3664-3670
    PubMedGoogle Scholar
  • 24 Jung DH, Lee YR, Kim SH. New synthetic routes to biologically interesting geranylated flavanones and geranylated chalcones: First total synthesis of (±)-prostratol F, xanthoangelol, and (±)-lespeol. Helv Chim Acta 2010; 93: 635-647
    CrossrefPubMedGoogle Scholar
  • 25 Mabry TJ, Markham KR, Thomas MB. The systematic identification of flavonoids. New York: Springer-Verlag; 1970: 227
    CrossrefGoogle Scholar
  • 26 Jin JH, Kim JS, Kang SS, Son KH, Chang HW, Kim HP. Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of Sophora flavescens . J Ethnopharmacol 2010; 127: 589-595
    CrossrefPubMedGoogle Scholar
  • 27 Villa FA, Lieske K, Gerwick L. Selective MyD88-dependent pathway inhibition by the cyanobacterial natural product malyngamide F acetate. Eur J Pharmacol 2010; 629: 140-146
    CrossrefPubMedGoogle Scholar
  • 28 Kim HK, Cheon BS, Kim YH, Kim SY, Kim HP. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure-activity relationships. Biochem Pharmacol 1999; 58: 759-765
    CrossrefPubMedGoogle Scholar
  • 29 Park KH, Park YD, Han JM, Im KR, Lee BW, Jeong Y, Jeonga TS, Lee WS. Anti-atherosclerotic and anti-inflammatory activities of catecholic xanthones and flavonoids isolated from Cudrania tricuspidata . Bioorg Med Chem Lett 2006; 16: 5580-5583
    CrossrefPubMedGoogle Scholar
  • 30 Peluso MR, Miranda CL, Hobbs DJ, Proteau RR, Stevens JF. Xanthohumol and related prenylated flavonoids inhibit inflammatory cytokine production in LPS-activated THP-1 monocytes: structure-activity relationships and in silico binding to myeloid differentiation protein-2 (MD-2). Planta Med 2010; 76: 1536-1543
    Article in Thieme ConnectPubMedGoogle Scholar