Download PDF
Planta Med 2014; 80(04): 277-282
DOI: 10.1055/s-0033-1360400
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Phyllanthus amarus Does Not Affect Hypernociception in Experimental Autoimmune Encephalomyelitis

Graziella Rigueira Molska
1   Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil
,
Giuseppina Negri
1   Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil
,
Lyvia Izaura Gomes Paula-Freire
1   Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil
,
Leandro Pires Araujo
2   Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil
,
Daniele Oliveira Köhn
1   Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil
,
Alexandre Salgado Basso
2   Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil
,
Elisaldo Araújo Carlini
3   Departamento de Medicina Preventiva, Universidade Federal de São Paulo, São Paulo, Brazil
› Author Affiliations
Further Information

Publication History

received 30 September 2013
revised 21 January 2014

accepted 24 January 2014

Publication Date:
07 March 2014 (online)

Also available at
    Permissions and Reprints

Abstract

Multiple sclerosis is an inflammatory disease of the central nervous system. Chronic pain is one of the main symptoms, affecting many patients. Studies show that the lignans or the apolar extracts of Phyllanthus amarus have antinociceptive effects in different animal models. To evaluate the antihypernociceptive effect of a hexanic extract of P. amarus in experimental autoimmune encephalomyelitis in mice, the chemical composition of the hexanic extract was analyzed by gas chromatography mass spectrometry. After EAE induction, animals were treated with the hexanic extract of P. amarus for 26 consecutive days. Motor coordination and mechanical hypernociception were evaluated on alternate days. The principal lignans found were phyllanthin, niranthin, and 5-demethoxyniranthin. The hexanic extract of P. amarus at a dose of 100, 200, or 400 mg/kg did not affect the development of the disease. The motor coordination and pain threshold of the treated animals were not altered in this experiment. In conclusion, in this test, the hexanic extract of P. amarus did not show evidence of antihypernociceptive activity in experimental autoimmune encephalomyelitis.

Key words

Phyllanthus amarus - Euphorbiaceae - pain - hypernociception - experimental autoimmune encephalomyelitis - lignans
 

  • References

  • 1 Alcaro MC, Papini AM. Contribution of peptides to multiple sclerosis research. Biopolymers 2006; 84: 349-367
    CrossrefPubMedSearch in Google Scholar
  • 2 Svendsen KB, Jensen TS, Overvad K, Hansen HJ, Koch-Henriksen N, Bach FW. Pain in patients with multiple sclerosis: a population-based study. Arch Neurol 2003; 60: 1089-1094
    CrossrefPubMedSearch in Google Scholar
  • 3 Ehde DM, Osborne TL, Hanley MA, Jensen MP, Kraft GH. The scope and nature of pain in persons with multiple sclerosis. Mult Scler 2006; 12: 629-638
    CrossrefPubMedSearch in Google Scholar
  • 4 Olechowski CJ, Truong JJ, Kerr BJ. Neuropathic pain behaviours in a chronic-relapsing model of experimental autoimmune encephalomyelitis (EAE). Pain 2009; 141: 156-164
    CrossrefPubMedSearch in Google Scholar
  • 5 Olechowski CJ, Parmar A, Miller B, Stephen J, Tenorio G, Tran K, Kerr BJ. A diminished response to formalin simulation reveals a role for the glutamate transporters in the altered pain sensitivity of mice with experimental autoimmune encephalomyelitis (EAE). Pain 2010; 149: 565-572
    CrossrefPubMedSearch in Google Scholar
  • 6 Thibault K, Calvino B, Pezet S. Characterisation of sensory abnormalities observed in an animal model of multiple sclerosis: a behavioural and pharmacological study. Eur J Pain 2011; 3: 1-16
    PubMedSearch in Google Scholar
  • 7 Patel JR, Tripathi P, Sharma V, Chauhan NS, Dixit VK. Phyllanthus amarus: ethnomedicinal uses, phytochemistry and pharmacology: a review. J Ethnopharmacol 2011; 138: 286-313
    CrossrefPubMedSearch in Google Scholar
  • 8 Singh M, Tiwari N, Shanker K, Verma RK, Gupta AK, Gupta MM. Two new lignans from Phyllanthus amarus. J Asian Nat Prod Res 2009; 11: 562-568
    CrossrefPubMedSearch in Google Scholar
  • 9 Foo LY. Amariinic acid and related ellagitannins from Phyllanthus amarus . Phytochemistry 1995; 39: 217-224
    CrossrefPubMedSearch in Google Scholar
  • 10 Kassuya CA, Silvestre A, Menezes-de-Lima jr. O, Marotta DM, Rehder VL, Calixto JB. Antiinflammatory and antiallodynic actions of the lignan niranthin isolated from Phyllanthus amarus. Evidence for interaction with platelet activating factor receptor. Eur J Pharmacol 2006; 54: 182-188
    PubMedSearch in Google Scholar
  • 11 Londhe JS, Devasagayam TPA, Foo LY, Ghaskadbi SS. Antioxidant activity of some polyphenol constituents of the medicinal plant Phyllanthus amarus Linn. Redox Rep 2008; 13: 199-207
    CrossrefPubMedSearch in Google Scholar
  • 12 Moronkola DO, Ogunwande IA, Oyewole IO, Baser KHC, Ozek T, Ozek G. Studies on the volatile oils of Momordica charantia L. (Cucurbitaceae) and Phyllanthus amarus Sch et Thonn (Euphorbiaceae). J Essent Oil Res 2009; 21: 393-399
    CrossrefPubMedSearch in Google Scholar
  • 13 Kupeli E, Erdemoglu N, Yesilada E, Sener B. Anti-inflammatory and antinociceptive activity of taxoids and lignans from the heartwood of Taxus baccata L. J Ethnopharmacol 2003; 89: 265-270
    CrossrefPubMedSearch in Google Scholar
  • 14 Kassuya CAL, Silvestre AA, Rehder VLG, Calixto JB. 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: 145-153
    CrossrefPubMedSearch in Google Scholar
  • 15 Kassuya CA, Leite DF, de Melo LV, Rehder VL, Calixto JB. Anti-inflammatory properties of extracts, fractions and lignans isolated from Phyllanthus amarus . Planta Med 2005; 71: 721-726
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Iranloye BO, Owoyele VB, Kelani OR, Olaleye SB. Analgesic activity of aqueous leaf extracts of Phyllanthus amarus . Afr J Med Med Sci 2011; 40: 47-50
    PubMedSearch in Google Scholar
  • 17 Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S. Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and replication. Eur J Clin Invest 1996; 26: 1069-1076
    CrossrefPubMedSearch in Google Scholar
  • 18 Guha G, Rajkumar V, Ashok KR, Mathew L. Aqueous extract of Phyllanthus amarus inhibits chromium (VI)-induced toxicity in MDA-MB-435S cells. Food Chem Toxicol 2010; 48: 396-401
    PubMedSearch in Google Scholar
  • 19 Raphael KR, Khuttan R. Inhibition of experimental gastric lesion and inflammation by Phyllanthus amarus extract. J Ethnopharmacol 2003; 87: 193-197
    CrossrefPubMedSearch in Google Scholar
  • 20 Kiemer AK, Hartung T, Huber C, Vollmar AM. Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX-2, and cytokines via the NF-kB pathway. J Hepatol 2003; 38: 289-297
    CrossrefPubMedSearch in Google Scholar
  • 21 Mahat MA, Patil BM. Evaluation of antiinflammatory activity of methanol extract of Phyllanthus amarus in experimental animal models. Indian J Pharm Sci 2007; 69: 33-36
    CrossrefPubMedSearch in Google Scholar
  • 22 Chang CC, Lien YC, Karin CS, Liu C, Lee SS. Lignans from Phyllanthus urinaria . Phytochemistry 2003; 63: 825-833
    CrossrefPubMedSearch in Google Scholar
  • 23 Krithika R, Mohankumar R, Verma RJ, Shrivastav PS, Mohamad IL, Gunasekaran P, Narasimhan S. Isolation, characterization and antioxidative effect of phyllanthin against CCl4-induced toxicity in HepG2 cell line. Chem Biol Interact 2009; 181: 351-358
    CrossrefPubMedSearch in Google Scholar
  • 24 Wang CY, Lee SS. Analysis and identification of lignans in Phyllanthus urinaria by HPLC-SPE-NMR. Phytochem Anal 2005; 16: 120-126
    CrossrefPubMedSearch in Google Scholar
  • 25 Chouhan HS, Singh SK. Phytochemical analysis, antioxidant and anti-inflammatory activities of Phyllanthus simplex . J Ethnopharmacol 2011; 137: 1337-1344
    CrossrefPubMedSearch in Google Scholar
  • 26 Elfahmi BS, Koulman A, Hackl T, Bos R, Kayser O, Woerdenbag HJ, Quax WJ. Lignans from cell suspension cultures of Phyllanthus niruri, an Indonesian medicinal plant. J Nat Prod 2006; 69: 55-58
    CrossrefPubMedSearch in Google Scholar
  • 27 Tripathi AK, Verma RK, Gupta AK, Gupta MM, Khanuja SPS. Quantitative determination of phyllanthin and hypophyllanthin in Phyllanthus species by high-performance thin layer chromatography. Phytochem Anal 2006; 17: 394-397
    CrossrefPubMedSearch in Google Scholar
  • 28 Santos ARS, Cechinel-Filho V, Yunes RA, Calixto JB. Further studies on the antinociceptive action of the hydroalcoholic extracts from plants of the genus Phyllanthus . J Pharm Pharmacol 1995; 47: 66-71
    CrossrefPubMedSearch in Google Scholar
  • 29 Catapan E, Otuki MF, Viana AM, Yunes RA, Bresciani LF, Ferreira J, Santos AR, Calixto JB, Cechinel-Filho V. Pharmacological activity and chemical composition of callus culture extracts from selected species of Phyllanthus . Pharmazie 2000; 12: 945-956
    PubMedSearch in Google Scholar
  • 30 Santos ARS, De Campos ROP, Miguel OG, Cechinel-Filho V, Siani AC, Yunes RA, Calixto JB. Antinociceptive properties of extracts of new species of plants of the genus Phyllanthus (Euphorbiaceae). J Ethnopharmacol 2000; 72: 229-238
    CrossrefPubMedSearch in Google Scholar
  • 31 Mali SM, Sinnathambi A, Kapase CU, Bodhankar SL, Mahadik KR. Anti-arthritic activity of standardised extract of Phyllanthus amarus in Freundʼs complete adjuvant induced arthritis. Biomed Aging Pathol 2011; 1: 185-190
    CrossrefPubMedSearch in Google Scholar
  • 32 Sud R, Spengler RN, Nader ND, Ignatowski TA. Antinociception occurs with a reversal in alpha(2)-adrenoceptor regulation of TNF production by peripheral monocytes/macrophages from pro- to anti-inflammatory. Eur J Pharmacol 2008; 588: 217-231
    CrossrefPubMedSearch in Google Scholar
  • 33 Murugaiyah V, Chan KL. Analysis of lignans from Phyllanthus niruri L. in plasma using a simple HPLC method with fluorescence detection and its application in a pharmacokinetic study. J Chromatogr B 2007; 852: 138-144
    CrossrefPubMedSearch in Google Scholar
  • 34 Chatterjee A, Chattopadhyay S, Bandyopadhyay SK. Biphasic effect of Phyllanthus emblica L. extract on NSAID-induced ulcer: an antioxidative trail weaved with immunomodulatory effect. Evid Based Complement Alternat Med 2010; 2011: 1-13
    PubMedSearch in Google Scholar