Anti-Inflammatory Properties of Extracts, Fractions and Lignans Isolated from Phyllanthus amarus

Abstract

This study assessed the anti-inflammatory effect of the extracts and purified lignans obtained from Phyllanthus amarus. Given orally, the hexane extract (HE), the lignan-rich fraction (LRF), or the lignans phyltetralin, nirtetralin, niranthin, but not hypophyllanthin or phyllanthin, inhibited carrageenan (Cg)-induced paw oedema and neutrophil influx. The HE, the LRF or nirtetralin also inhibited the increase of IL1-β tissue levels induced by Cg. Furthermore, bradykinin (BK)-, platelet activating factor (PAF)- and endothelin-1 (ET-1)-induced paw oedema were significantly inhibited by the HE or LRF while histamine- and substance P-induced paw oedema were unaffected. Finally, nirtetralin or phyltetralin caused inhibition of paw oedema induced by PAF or ET-1. These results show that the HE, the LRF and the lignans niranthin, phyltetralin and nirtetralin exhibited marked anti-inflammatory properties and suggest that these lignans seem to be the main active principles responsible for the anti-inflammatory properties reported for the HE of P. amarus.

Key words

Phyllanthus amarus - anti-inflammatory action - paw oedema - myeloperoxidase - carrageenan

References

• 1 Unander D W, Webster G L, Blumberg B S. Usage and bioassays in Phyllanthus (Euphorbiaceae). IV. Clustering of antiviral uses and other effects.  J Ethnopharmacol. 1995;  45 1-18
• 2 Calixto J B, Santos A R, Cechinel Filho V, Yunes R A. A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential.  Med Res Rev. 1998;  18 225-58
• 3 Venkateswaran P S, Millman I, Blumberg B S. Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies.  Proc Natl Acad Sci USA. 1987;  84 274-8
• 4 Wang B E. Treatment of chronic liver diseases with traditional Chinese medicine.  J Gastroenterol Hepatol. 2000;  15 S67-70
• 5 Notka F, Meier G R, Wagner R. Inhibition of wild-type human immunodeficiency virus and reverse transcriptase inhibitor-resistant variants by Phyllanthus amarus .  Antiviral Res. 2003;  58 175-86
• 6 Rajeshkumar N V, Kuttan R. Phyllanthus amarus extract administration increases the life span of rats with hepatocellular carcinoma.  J Ethnopharmacol. 2000;  73 215-9
• 7 Raphael K R, Kuttan R. Inhibition of experimental gastric lesion and inflammation by Phyllanthus amarus extract.  J Ethnopharmacol. 2003;  87 193-7
• 8 Kiemer A K, Hartung T, Huber C, Vollmar A M. Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-kappaB pathway.  J Hepatol. 2003;  38 289-97
• 9 Kassuya C AL, Silvestre A A, Rehder V L, Calixto J B. Anti-allodynic and anti-oedematogenic properties of the extract and lignans from Phyllanthus amarus in models of persistent inflammatory and neuropathic pain.  Eur J Pharmacol. 2003;  478 145-53
• 10 Bastos J K, Carvalho J C, de Souza G H, Pedrazzi A H, Sarti S J. Anti-inflammatory activity of cubebin, a lignan from the leaves of Zanthoxyllum naranjillo Griseb.  J Ethnopharmacol. 2001;  75 279-82
• 11 MacRae W D, Towers G HN. Biological activities of lignans.  Phytochemistry. 1984;  23 1207-20
• 12 Hussain R A, Dickey J J, Rosser M P, Marson J A, Kozlowski M R. A novel class of non-peptidic endothelin antagonists isolated from the medicinal herb Phyllanthus niruri .  J Nat Prod. 1995;  58 1515-20
• 13 Somanabandhu A, Nitayangkura S, Mahidol C, Ruchirawat S, Likhitwitayawuid K, Shieh H L, Chai H, Pezzuto J M, Cordell G A. ¹H- and ¹³C-NMR assignments of phyllanthin and hypophyllanthin: lignans that enhance cytotoxic responses with cultured multidrug-resistant cells.  J Nat Prod. 1993;  56 233-9
• 14 Anjaneyulu A SR, Jaganmohan R K, Ramachandra R L, Subrahmanyan C. Isolation and structural elucidation of tree new lignans from the leaves of Phyllanthus niruri Linn.  Tetrahedron. 1973;  29 1291-8
• 15 Correa C R, Calixto J B. Evidence for participation of B1 and B2 kinin receptors in formalin-induced nociceptive response in the mouse.  Br J Pharmacol. 1993;  110 193-8
• 16 De Young L M, Kheifets J B, Ballaron S J, Young J M. Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents.  Agents Actions. 1989;  26 335-41
• 17 Pinheiro R M, Calixto J B. Effect of the selective COX-2 inhibitors, celecoxib and rofecoxib in rat acute models of inflammation.  Inflamm Res. 2002;  51 603-10
• 18 André E, Ferreira J, Malheiros A, Yunes R A, Calixto J B. Evidence for the involvement of vanilloid receptor in the antinociception produced by the dialdeydes unsaturated sesquiterpenes polygodial and drimanial in rats.  Neuropharmacology. 2004;  46 590-7
• 19 Calixto J B, Otuki M F, Santos A R. Anti-inflammatory compounds of plant origin. Part I. Action on arachidonic acid pathway, nitric oxide and nuclear factor kappa B (NF-kappaB).  Planta Med. 2003;  69 973-83
• 20 Calixto J B, Campos M M, Otuki M F, Santos A R. Anti-inflammatory compounds of plant origin. Part II. Modulation of pro-inflammatory cytokines, chemokines and adhesion molecules.  Planta Med. 2004;  70 93-103
• 21 Graham M F, Willey A, Zhu Y N, Yager D R, Sugerman H J, Diegelmann R F. Corticosteroids repress the interleukin 1 beta-induced secretion of collagenase in human intestinal smooth muscle cells.  Gastroenterology. 1997;  113 1924-9
• 22 Oluyomi A O, Nguyen H, Towbin H, Dawson J, Vosbeck K. Differential effects of prednisolone and indomethacin on zymosan-induced inflammation in a modified murine tissue-chamber model.  Inflamm Res. 1995;  44 350-6
• 23 Evangelou A M. Platelet-activating factor (PAF): implications for coronary heart and vascular diseases.  Prostaglandins Leukot Essent Fatty Acids. 1994;  50 1-28
• 24 Bertelli A, Clerico A, Chicca A, Giovannini I, Gorio A, Romano M A. Role of endothelin-1 in carrageenan-induced inflammation.  Int J Tissue Reactions Exp and Clin Asp. 1992;  14 225-30
• 25 Lee I S, Jung K Y, Oh S R, Park S H, Ahn K S, Lee H K. Structure-activity relationships of lignans from Schisandra chinensis as platelet activating factor antagonists.  Biol Pharm Bull. 1999;  22 265-7