Planta Med 2015; 81(18): 1688-1696
DOI: 10.1055/s-0035-1557837
Biological and Pharmacological Activitiy
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Antinociceptive and Anti-inflammatory Activities of the Methanolic Extract from the Stem Bark of Lophanthera lactescens

Gabriela Carmelinda Martins dos Santos
1   Laboratório de Farmacologia, Departamento de Ciências Fisiológicas, Instituto de Biologia, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Renata Duarte Fernandes
2   Laboratório de Produtos Naturais, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Tarcila Rocha Barros
2   Laboratório de Produtos Naturais, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Heber dos Santos Abreu
3   Instituto de Floresta, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Luciano Ramos Suzart
2   Laboratório de Produtos Naturais, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Mário Geraldo de Carvalho
2   Laboratório de Produtos Naturais, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Raimundo Braz Filho
2   Laboratório de Produtos Naturais, Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Bruno Guimarães Marinho
1   Laboratório de Farmacologia, Departamento de Ciências Fisiológicas, Instituto de Biologia, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
› Author Affiliations
Further Information

Publication History

received 15 January 2015
revised 01 April 2015

accepted 21 June 2015

Publication Date:
26 August 2015 (online)

Abstract

Lophanthera lactescens is a medicinal plant commonly used in traditional medicine to relieve fever and pain in inflammatory processes. In the present study, the in vivo antinociceptive and anti-inflammatory effects of the methanolic extract from L. lactescens have been investigated. Antinociceptive activity was evaluated through writhing, formalin, and tail flick tests, while the anti-inflammatory activity was evaluated through paw oedema and air pouch tests in mice. A phytochemical analysis was performed. The extract produced significant inhibition on nociception induced by acetic acid-induced abdominal writhing, formalin, and tail flick tests, and on inflammation induced by oedema and air pouch tests. The previous administration of atropine and glibenclamide reduced the antinociceptive effect produced by the methanolic extract from L. lactescens on the tail flick test in 89 % and 66 %, respectively. The methanolic extract had no significant effect in the open field test. No intoxication symptoms were observed in the animals administered orally at increasing doses up to 2000 mg/kg. The methanolic extract from the stem bark of L. lactescens possesses antinociceptive properties on models of acute pain induced by chemical and thermal stimuli as well as in models of inflammation and further suggests that this anti-inflammatory activity might involve inhibition of the proinflammatory cytokines, and the antinociceptive activity might involve participation of the cholinergic system and adenosine triphosphate-dependent K+ channel.

Supporting Information

 
  • References

  • 1 Abreu HS, Braz-Filho R, Gottlieb HE, Shoolery JN. A nor-triterpenoid from Lophantera lactescens . Phytochemistry 1990; 29: 2257-2261
  • 2 Armstrong W. Recent trends in research on inflammation and treatment of inflammatory diseases. Richmond: PJB Publications; 1991: 199
  • 3 Olesen AE, Andresen T, Staahl C, Drewes AM. Human experimental pain models for assessing the therapeutic efficacy of analgesic drugs. Pharmacol Rev 2012; 64: 722-779
  • 4 Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001; 413: 203-210
  • 5 Le Bars D, Gozariu M, Cadden S. Animal models of nociception. Pharmacol Rev 2001; 53: 597-652
  • 6 Millan MJ. The induction of pain: an integrative review. Prog Neurobiol 1999; 57: 1-164
  • 7 Jage J. Opioid tolerance and dependence – do they matter?. Eur J Pain 2005; 9: 157-162
  • 8 Mitchell JA, Warner TD. COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs. Nat Rev Drug Discov 2006; 5: 75-86
  • 9 Kennedy JD. Neuropathic pain: molecular complexity underlies continuing unmet medical need. J Med Chem 2007; 50: 2547-2556
  • 10 Mao J. Translational pain research: achievements and challenges. J Pain 2009; 10: 1001-1011
  • 11 Abreu HS. Estudos dos constituintes químicos da espécie Lophanthera lactescens Ducke (MSC thesis). Rio de Janeiro: Universidade Federal Rural do Rio de Janeiro; 1985
  • 12 Corrêa GM, Abreu VGC, Martins DAA, Takahashi JA, Fontoura HS, Cara DC, Piló-Veloso D, Alcântara AFC. Anti-inflammatory and antimicrobial activities of steroids and triterpenes isolated from aerial parts of Justicia acuminatissima (Acanthaceae). Int J Pharm Pharm Sci 2014; 6: 75-81
  • 13 Kongduang D, Wungsintaweekul J, De-Eknamkul W. Biosynthesis of β-sitosterol and stigmasterol proceeds exclusively via the mevalonate pathway in cell suspension cultures of Croton stellatopilosus . Tetrahedron Lett 2008; 49: 4067-4072
  • 14 Ikeda Y, Ueno A, Naraba H, Ohishi S. Involvement of vanilloid receptor R1 and prostanoids in the acid-induced writhing responses of mice. Life Sci 2001; 69: 2911-2919
  • 15 Kuraishi Y, Harada Y, Aratani S, Satoh M, Takagi H. Separate involvement of the spinal noradrenergic and serotonergic systems in morphine analgesia: the differences in mechanical and thermal algesic tests. Brain Res 1983; 273: 245-252
  • 16 Tassinari D, Masi A, Sartori S, Nielsen I, Ravaioli A. Atypical absorption of morphine sulphate through oral mucosa: an usual case of acute opioid poisoning. J Pain Symptom Manage 1995; 10: 405-407
  • 17 Lian B, Vera-Portocarrero L, King T, Ossipov MH, Porreca F. Opioid-induced latent sensitization in a model of non-inflammatory viscerosomatic hypersensitivity. Brain Res 2010; 1358: 64-70
  • 18 Jones PG, Dunlop J. Targeting the cholinergic system as a therapeutic strategy for the treatment of pain. Neuropharmacology 2007; 53: 197-206
  • 19 Choi YS, Billings JA. Opioid antagonists: a review of their role in palliative care, focusing on use in opioid-related constipation. J Pain Symptom Manage 2002; 24: 71-90
  • 20 Rodrigues AR, Duarte ID. The peripheral antinociceptive effect induced by morphine is associated with ATP-sensitive K+ channels. Br J Pharmacol 2000; 129: 110-114
  • 21 Ortiz MI, Granados-Soto V, Castaneda-Hernandez G. The NO-cGMP-K+ channel pathway participates in the antinociceptive effect of diclofenac, but not of indomethacin. Pharmacol Biochem Behav 2003; 76: 187-195
  • 22 Bhandare AM, Kshirsagar AD, Vyawahare NS, Hadambar AA, Thorve VS. Potential analgesic, anti-inflammatory and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut. Food Chem Toxicol 2010; 48: 3412-3417
  • 23 Guang-Ming Y, Dong W, Wei T, Xing C, Lin-Qian F, Fang-Fang Z, Huan Y, Bao-Chang C. Anti-inflammatory and antioxidant activities of Oxytropis falcate fractions and its possible anti-inflammatory mechanism. Chin J Nat Med 2010; 8: 0285-0292
  • 24 Eddouks M, Chattopadhyay D, Zeggwagh NA. Animal models as tools to investigate antidiabetic and anti-inflammatory plants. Evid Based Complement Alternat Med 2012; 2012: 1-14
  • 25 Ryan GB, Majno G. Acute inflammation. Am J Pathol 1977; 86: 185-274
  • 26 Bevilacqua MP, Nelson RM. Selectins. J Clin Invest 1993; 91: 379-387
  • 27 Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol 2003; 24: 25-29
  • 28 Fröde TS, Medeiros YS. Myeloperoxidase and adenosine-deaminase levels in the pleural fluid leakage induced by carrageenan in the mouse model of pleurisy. Mediators Inflamm 2001; 10: 223-227
  • 29 Fröde TS, Souza GE, Calixto JB. The modulatory role played by TNF-alpha and IL-1 beta in the inflammatory responses induced by carrageenan in the mouse model of pleurisy. Cytokine 2001; 13: 162-168
  • 30 Menegazzi M, Di Paola R, Mazzon E, Genovese T, Crisafulli C, Dal Bosco M, Zou Z, Suzuki H, Cuzzocrea S. Glycyrrhizin attenuates the development of carrageenan-induced lung injury in mice. Pharmacol Res 2008; 58: 22-31
  • 31 Schein CH. The shape of the messenger: using protein structure information to design novel cytokine-based therapeutics. Curr Pharm Des 2002; 8: 2113-2129
  • 32 Ebnet K, Vestweber D. Molecular mechanisms that control leukocyte extravasation: the selections and the chemokines. Histochem. Cell Biol 1999; 112: 1-23
  • 33 Dinarello CA. Proinflammatory cytokines. Chest 2000; 118: 503-508
  • 34 Matos FJA. Introdução à fitoquímica experimental. 2nd. edition. Fortaleza: Edições UFC; 1997: 320-323
  • 35 Guilhon CC, Raymundo LJRP, Alviano DS, Blank AF, Arrigoni-Blank MF, Matheus ME, Cavalcanti SCH, Alviano CS, Fernandes PD. Characterisation of the anti-inflammatory and anti-nociceptive activities and the mechanism of the action of Lippia gracilis essential oil. J Ethnopharmacol 2011; 135: 406-413
  • 36 Koster R, Anderson M, De Beer EJ. Acetic acid for analgesic screening. Fed Proc 1959; 18: 412
  • 37 Hunskaar S, Berge OG, Hole K. Dissociation between anti-nociceptive an anti-inflammatory effects of acetylsalicylic and indomethacin in the formalin test. Pain 1986; 25: 125-132
  • 38 DʼAmour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther 1941; 72: 74-79
  • 39 Ferreira SH. Oedema and increased vascular permeability. In: Vane JR, Van Arman CG, editors Handbook of experimental pharmacology. New York: Springer-Verlag; 1979: 75-91
  • 40 Vigil SV, De Liz R, Medeiros YS, Fröde TS. Efficacy of tacrolimus in inhibiting inflammation caused by carrageenan in a murine model of air pouch. Transpl Immunol 2008; 19: 25-29
  • 41 Barros HM, Tannhauser MA, Tannhauser SL, Tannhauser M. Enhanced detection of hyperactivity after drug withdrawal with a simple modification of the open-field apparatus. J Pharmacol Methods 1991; 26: 269-275
  • 42 World Health Organization. General guidelines for methodologies on research and evaluation of traditional medicine. Geneva: WHO; 2000: 28-29
  • 43 The Organization of Economic Co-operation and Development (OECD). OECD Guidelines for the Testing of Chemicals: 420 Acute Oral Toxicity. Paris: OECD Publishing; 2002: 1-6
  • 44 Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol 1983; 54: 275-287