Skip to main content
SpringerLink
Log in

Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var. grisea

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

In the present study, siaresinolic acid (siaresinol, SA) was isolated from the leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti-inflammatory activity. The antinociceptive effect of SA was investigated in mice using different animal models to study pain. In the acetic acid-induced writhing test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h before a pain stimulus significantly reduced the nociceptive response (by 42.3, 68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive effect induced by SA in the writhing test, suggesting that the K+ATP channel pathway might be involved in its mechanism of action. In the formalin test, SA (1 mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating an anti-inflammatory effect. In the hot plate test, there was no significant difference in nociceptive behavior. In the rota-rod test, it was verified that a high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice. In the pleurisy model, induced by carrageenan, treatment with SA inhibited important events involved in inflammatory responses, namely leukocyte influx, plasma leakage, and increased inflammatory mediators (TNF-α, IL-1β, and chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at concentrations ranging from 1 to 200 μg/mL. These results suggest, for the first time, that SA attenuates nociceptive behavior through mechanisms involving receptors for ATP-dependent potassium channels, in addition to suppressing acute inflammatory responses.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Bremer B, Manen JF (2000) Phylogeny and classification of the subfamily Rubioideae (Rubiaceae). Plant Syst Evol 225:43–72

    Article  CAS  Google Scholar 

  2. Taylor CM, Steyermark JA, Delprete PG, Vicentini A, Cortés R, Zappi D, Persson C, Costa CB, Anunciação E (2004) Rubiaceae. In: Berry PE, Yatskievych K, Holst BK (eds) Flora of the Venezuelan Guayana. Missouri Botanical Garden Press, St. Louis, pp 497–848

    Google Scholar 

  3. Pereira ZV, Carvalho-Okano RM, Garcia FC (2006) Rubiaceae Juss. da Reserva Florestal Mata do Paraíso, Viçosa, MG, Brasil. Acta Bot Brasilica 20:207–224

    Article  Google Scholar 

  4. Roumy V, Garcia-Pizango G, Gutierrez-Choquevilca AL, Ruiz L, Jullian V, Winterton P, Fabre N, Moulis C, Valentin A (2007) Amazonian plants from Peru used by Quechua and Mestizo to treat malaria with evaluation of their activity. J Ethnopharmacol 112:482–489

    Article  CAS  PubMed  Google Scholar 

  5. Hirschmann GS, De Arias AR (1990) A survey of medicinal plants of Minas Gerais, Brazil. J Ethnopharmacol 29:159–172

    Article  CAS  PubMed  Google Scholar 

  6. Awad R, Ahmed F, Bourbonnais-Spear N, Mullally M, Ta CA, Tang A, Merali Z, Maquin P, Caal F, Cal V, Poveda L, Vindas PS, Trudeau VL, Arnason JT (2009) Ethnopharmacology of Q’eqchi’ Maya antiepileptic and anxiolytic plants: effects on the GABAergic system. J Ethnopharmacol 125:257–264

    Article  CAS  PubMed  Google Scholar 

  7. Comini LR, Fernandez IM, Rumie Vittar NB, Núñez Montoya SC, Cabrera JL, Rivarola VA (2011) Photodynamic activity of anthraquinones isolated from Heterophyllaea pustulata Hook f. (Rubiaceae) on MCF-7c3 breast cancer cells. Phytomedicine 18:1093–1095

    Article  CAS  PubMed  Google Scholar 

  8. de Oliveira AM, Conserva LM, de Souza Ferro JN, de Almeida Brito F, Lyra Lemos RP, Barreto E (2012) Antinociceptive and anti-inflammatory effects of octacosanol from the leaves of Sabicea grisea var. grisea in mice. Int J Mol Sci 13:1598–1611

    Article  PubMed Central  PubMed  Google Scholar 

  9. Suksamrarn A, Tanachatchairatana T, Kanokmedhakul S (2003) Antiplasmodial triterpenes from twigs of Gardenia saxatilis. J Ethnopharmacol 88:275–277

    Article  CAS  PubMed  Google Scholar 

  10. Heitzman ME, Neto CC, Winiarz E, Vaisberg AJ, Hammond GB (2005) Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Phytochemistry 66:5–29

    Article  CAS  PubMed  Google Scholar 

  11. Karou SD, Tchacondo T, Ilboudo DP, Simpore J (2011) Sub-Saharan Rubiaceae: a review of their traditional uses, phytochemistry and biological activities. Pak J Biol Sci 14:149–169

    Article  CAS  PubMed  Google Scholar 

  12. Conserva LM, Ferreira JC Jr (2012) Borreria and Spermacoce species (Rubiaceae): a review of their ethnomedicinal properties, chemical constituents, and biological activities. Pharmacogn Rev 6:46–55

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Wu GS, Lu JJ, Guo JJ, Li YB, Tan W, Dang YY, Zhong ZF, Xu ZT, Chen XP, Wang YT (2012) Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells. Fitoterapia 83:408–414

    Article  CAS  PubMed  Google Scholar 

  14. Chung PY, Chung LY, Navaratnam P (2014) Potential targets by pentacyclic triterpenoids from Callicarpa farinosa against methicillin-resistant and sensitive Staphylococcus aureus. Fitoterapia 94:48–54

    Article  CAS  PubMed  Google Scholar 

  15. Zhang Y, Peng Y, Li L, Zhao L, Hu Y, Hu C, Song S (2013) Studies on cytotoxic triterpene saponins from the leaves of Aralia elata. Food Chem 138:208–213

    Article  CAS  PubMed  Google Scholar 

  16. Gnoatto SC, Susplugas S, Dalla Vechia L, Ferreira TB, Dassonville-Klimpt A, Zimmer KR, Demailly C, Da Nascimento S, Guillon J, Grellier P, Verli H, Gosmann G, Sonnet P (2008) Pharmacomodulation on the 3-acetylursolic acid skeleton: design, synthesis, and biological evaluation of novel N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-O-acetylursolamide derivatives as antimalarial agents. Bioorg Med Chem 16:771–782

    Article  CAS  PubMed  Google Scholar 

  17. Kinoshita K, Akiba M, Saitoh M, Ye Y, Koyama K, Takahashi K, Kondo N, Yuasa H (1998) Antinociceptive effect of triterpenes from cacti. Pharm Biol 36:50–55

    Article  CAS  Google Scholar 

  18. Akihisa T, Yasukawa K, Oinuma H, Kasahara Y, Yamanouchi S, Takido M, Kumaki K, Tamura T (1996) Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects. Phytochemistry 43:1255–1260

    Article  CAS  PubMed  Google Scholar 

  19. Song Y, Xu B, Cai W (2013) Active substances and in vitro anti-diabetic effects of a traditional folk remedy Bian-Que Triple-Bean Soup as affected by the boiling time. Food Funct 4:635–643

    Article  CAS  PubMed  Google Scholar 

  20. Teles HL, Hemerly JP, Paulettit PM, Pandolfi JR, Araujot AR, Valentini SR, Young MC, Bolzani VS, Silva DH (2005) Cytotoxic lignans from the stems of Styrax camporum (Styracaceae). Nat Prod Res 19:319–323

    Article  CAS  PubMed  Google Scholar 

  21. Mahato SB, Kundu AP (1994) 13C NMR spectra of pentacyclic triterpenoids—a compilation and some salient features. Phytochemistry 37:1517–1575

    Article  CAS  Google Scholar 

  22. Wang XL, Hay AE, Matheeussen A, Gupta MP, Hostettmann K (2011) Structure elucidation and NMR assignments of two new triterpenoids from the stems of Paragonia pyramidata (Bignoniaceae). Magn Reson Chem 49:184–189

    Article  CAS  PubMed  Google Scholar 

  23. de Barros BS, da Silva JP, de Souza Ferro JN, Agra IK, de Almeida Brito F, Albuquerque ED, Caetano LC, Barreto E (2011) Methanol extract from mycelium of endophytic fungus Rhizoctonia sp. induces antinociceptive and anti-inflammatory activities in mice. J Nat Med 65:526–531

    Article  PubMed  Google Scholar 

  24. de Souza Ferro JN, da Silva JP, Conserva LM, Barreto E (2013) Leaf extract from Clusia nemorosa induces an antinociceptive effect in mice via a mechanism that is adrenergic systems dependent. Chin J Nat Med 11:385–390

    PubMed  Google Scholar 

  25. Guimarães AG, Xavier MA, de Santana MT, Camargo EA, Santos CA, Brito FA, Barreto EO, Cavalcanti SC, Antoniolli AR, Oliveira RC, Quintans-Júnior LJ (2012) Carvacrol attenuates mechanical hypernociception and inflammatory response. Naunyn Schmiedebergs Arch Pharmacol 385:253–263

    Article  PubMed  Google Scholar 

  26. Reddy GC, Rangaswami S, Sunder R (1977) Triterpenoids of the stem bark of Gardenia gummifera. Planta Med 32:206–211

    Article  CAS  PubMed  Google Scholar 

  27. Guimarães AG, Oliveira GF, Melo MS, Cavalcanti SC, Antoniolli AR, Bonjardim LR, Silva FA, Santos JP, Rocha RF, Moreira JC, Araújo AA, Gelain DP, Quintans-Júnior LJ (2010) Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol. Basic Clin Pharmacol Toxicol 107:949–957

    Article  PubMed  Google Scholar 

  28. Le Bars D, Gozariu M, Cadden SW (2001) Animal models of nociception. Pharmacol Rev 53:597–652

    PubMed  Google Scholar 

  29. Dirig DM, Isakson PC, Yaksh TL (1998) Effect of COX-1 and COX-2 inhibition on induction and maintenance of carrageenan-evoked thermal hyperalgesia in rats. J Pharmacol Exp Ther 285:1031–1038

    CAS  PubMed  Google Scholar 

  30. Ling H, Jia X, Zhang Y, Gapter LA, Lim YS, Agarwal R, Ng KY (2010) Pachymic acid inhibits cell growth and modulates arachidonic acid metabolism in nonsmall cell lung cancer A549 cells. Mol Carcinog 49:271–282

    CAS  PubMed  Google Scholar 

  31. Xiao ZY, Zheng QY, Jiang YY, Zhou B, Yin M, Wang HB, Zhang JP (2004) Effects of esculentoside A on production of interleukin-1, 2, and prostaglandin E2. Acta Pharmacol Sin 25:817–821

    CAS  PubMed  Google Scholar 

  32. Katyal J, Gupta YK (2012) Dopamine release is involved in antinociceptive effect of theophylline. Int J Neurosci 122:17–21

    Article  CAS  PubMed  Google Scholar 

  33. Shannon HE, Lutz EA (2002) Comparison of the peripheral and central effects of the opioid agonists loperamide and morphine in the formalin test in rats. Neuropharmacology 42:253–261

    Article  CAS  PubMed  Google Scholar 

  34. Meotti FC, Fachinetto R, Maffi LC, Missau FC, Pizzolatti MG, Rocha JB, Santos AR (2007) Antinociceptive action of myricitrin: involvement of the K+ and Ca2+ channels. Eur J Pharmacol 567:198–205

    Article  CAS  PubMed  Google Scholar 

  35. Ramachandran V, Saravanan R (2013) Efficacy of asiatic acid, a pentacyclic triterpene on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats. Phytomedicine 20:230–236

    Article  CAS  PubMed  Google Scholar 

  36. Han XH, Liu P, Zhang YY, Zhang N, Chen FR, Cai JF (2011) Astragaloside IV regulates expression of ATP-sensitive potassium channel subunits after ischemia-reperfusion in rat ventricular cardiomyocytes. J Tradit Chin Med 31:321–326

    Article  PubMed  Google Scholar 

  37. Longhi-Balbinot DT, Martins DF, Lanznaster D, Silva MD, Facundo VA, Santos AR (2011) Further analyses of mechanisms underlying the antinociceptive effect of the triterpene 3beta, 6beta, 16beta-trihydroxylup-20(29)-ene in mice. Eur J Pharmacol 653:32–40

    Article  CAS  PubMed  Google Scholar 

  38. Yamamoto T, Nozaki-Taguchi N (2002) The role of cyclooxygenase-1 and -2 in the rat formalin test. Anesth Analg 94:962–967

    Article  CAS  PubMed  Google Scholar 

  39. Staahl C, Drewes AM (2004) Experimental human pain models: a review of standardised methods for preclinical testing of analgesics. Basic Clin Pharmacol Toxicol 95:97–111

    Article  CAS  PubMed  Google Scholar 

  40. Farias JAC, Ferro JNS, Silva JP, Agra IKR, Oliveira FM, Candea ALP, Conte FP, Ferraris FK, Henriques Md, Conserva LM, Barreto E (2012) Modulation of inflammatory processes by leaves extract from Clusia nemorosa both in vitro and in vivo animal models. Inflammation 35(2):764–771

    Article  PubMed  Google Scholar 

  41. Lopes-Martins RA, Albertini R, Martins PS, Bjordal JM, Faria Neto HC (2005) Spontaneous effects of low-level laser therapy (650 nm) in acute inflammatory mouse pleurisy induced by carrageenan. Photomed Laser Surg 23:377–381

    Article  PubMed  Google Scholar 

  42. Ferreira RG, Matsui TC, Godin AM, Gomides LF, Pereira-Silva PE, Duarte ID, Menezes GB, Coelho MM, Klein A (2012) Neutrophil recruitment is inhibited by nicotinamide in experimental pleurisy in mice. Eur J Pharmacol 685:198–204

    Article  CAS  PubMed  Google Scholar 

  43. Yao L, Yago T, Shao B, Liu Z, Silasi-Mansat R, Setiadi H, Lupu F, McEver RP (2013) Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil migration in mice. Blood 122:3832–3842

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Carrero R, Cerrada I, Lledó E, Dopazo J, García-García F, Rubio MP, Trigueros C, Dorronsoro A, Ruiz-Sauri A, Montero JA, Sepúlveda P (2012) IL1beta induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-kappaB. Stem Cell Rev 8:905–916

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Estado de Alagoas (FAPEAL) (Brazil).

Conflict of interest

There is no conflict of interest among the authors.

Author information

Authors and Affiliations

  1. Instituto de Química e Biotecnologia, Universidade Federal de Alagoas, Maceió, AL, 57072-970, Brazil

    Anderson Marques de Oliveira & Lucia M. Conserva

  2. Laboratório de Biologia Celular, Núcleo de Pesquisa Multidisciplinar, Universidade Federal de Alagoas, Campus A.C. Simões, s/n. Tabuleiro dos Martins, Maceió, AL, 57072-970, Brazil

    Almair Ferreira de Araújo, Jamylle Nunes de Souza Ferro & Emiliano Barreto

  3. Instituto Federal de Educação, Ciência e Tecnologia da Bahia, Vitória da Conquista, BA, 45075-265, Brazil

    Anderson Marques de Oliveira

  4. Instituto do Meio Ambiente do Estado de Alagoas, Maceió, AL, 57017-320, Brazil

    Rosangela P. Lyra Lemos

Authors
  1. Anderson Marques de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Almair Ferreira de Araújo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rosangela P. Lyra Lemos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucia M. Conserva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jamylle Nunes de Souza Ferro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emiliano Barreto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emiliano Barreto.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Oliveira, A.M., de Araújo, A.F., Lyra Lemos, R.P. et al. Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var. grisea . J Nat Med 69, 232–240 (2015). https://doi.org/10.1007/s11418-014-0883-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-014-0883-3

Keywords

Search

Navigation