Download PDF
Planta Med 2021; 87(10/11): 896-906
DOI: 10.1055/a-1497-0239
Biological and Pharmacological Activity
Original Papers

Phytochemical Analysis and Antinociceptive Properties of Hydroalcoholic Extracts of Aleurites moluccanus Bark[ # ]

Márcia Maria de Souza
1   Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
,
Luiz G. R. D. Chagas
1   Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
,
Ana Elisa Gonçalves
1   Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
,
Marcelo Tomczak
1   Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
,
Simone Reichert
1   Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
,
Ivania T. A. Schuquel
2   Universidade Estadual de Maringá (UEM), Departamento de Química, Maringá, Paraná State, Brazil
,
Valdir Cechinel-Filho
1   Universidade do Vale do Itajaí (UNIVALI), Escola de Ciências da Saúde, Itajaí, Santa Catarina State, Brazil
,
Christiane Meyre-Silva 
3   Pós-graduação em Farmácia. Universidade Federal de Santa Catarina (UFSC), Bloco JK, Campus Reitor João David Ferreira Lima, Trindade, Florianópolis, Santa Catarina State, Brazil
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Aleurites moluccanus is used in folk medicine to treat many diseases including pain and inflammatory processes in general. Considering the potential of the leaf extract, evidenced in a previous study, the present study investigates the antinociceptive and anti-inflammatory properties of the hydroethanolic extract of A. moluccanus bark and isolated compounds in animal models of pain. The antinociceptive and anti-inflammatory activities of A. moluccanus bark were evaluated through hyperalgesia induced by carrageenan, PGE2, cytokines, bradykinin, epinephrine, Freundʼs complete adjuvant, and lipopolysaccharide. Five compounds were isolated from the dichloromethane bark extract: acetyl aleuritolic acid, atraric acid, spruceanol, (5β,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one and sonderianol. To optimize the extraction conditions, ethanol 50, 70, and 90°GL were used as extracting solvent, in a 1 : 20 (w/v) drug : solvent ratio, under stirring at room temperature for 4 h. The extracts were named AMC50, AMC70, and AMC90, respectively. These extracts were administered to mice (250 mg/kg, p. o.) with reduced mechanical hyperalgesia activity in the carrageenan test. Of these, AMC90 showed the best results. Pure (5β,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one showed a beneficial effect for up to 48 hours after the administration of carrageenan, while acetyl aleuritolic acid was effective only in the first hour. AMC90 was able to reverse the analgesia induced only by prostaglandin E2 and tumor necrosis factor. We also induced hyperalgesia using the lipopolysaccharide and Freundʼs complete adjuvant models, with positive results. These results support the antinociceptive and anti-inflammatory activity of A. moluccanus bark extract. The observed effects are partly due to the presence of acetyl aleuritolic acid, atraric acid, and (5β,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one.

Key words

Euphorbiaceae - Aleurites moluccanus - antinociceptive - diterpene - hyperalgesia

# Dedicated to Professor Arnold Vlietinck on the occasion of his 80th birthday.




Publication History

Received: 04 January 2021

Accepted after revision: 30 April 2021

Article published online:
25 May 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Yeung YT, Aziz F, Guerrero-Castila A, Arguelles S. Signaling pathways in inflammation and anti-inflammatory therapies. Curr Pharm Des 2018; 24: 1449-1484
    CrossrefPubMedGoogle Scholar
  • 2 Tasneem S, Liu B, Li B, Choudharu MI, Wang W. Molecular pharmacology of inflammation: medicinal plants as anti-inflammatory agents. Pharmacol Res 2019; 139: 126-140
    CrossrefPubMedGoogle Scholar
  • 3 Duke JA. Handbook of medicinal Herbs. Boca Raton, USA: CRC Press; 1991
    Google Scholar
  • 4 Dunfors B, Andrews L, Ayau M, Honda LI, Williams JS. Hawaiians of Old. 3th ed. Honolulu: Bess Press; 2002
    Google Scholar
  • 5 Meyre-Silva C, Mora TC, Santos ARS, Dal-Magro J, Yunes RA, Cechinel-Filho V. Preliminary phytochemical and pharmacological studies of Aleurites moluccana leaves (L.) Willd. Phytomedicine 1998; 5: 109-113
    CrossrefPubMedGoogle Scholar
  • 6 Quintão NLM, Meyre-Silva C, Silva GF, Antonialli CS, Rocha LW, Lucinda-Silva RM, Malheiros A, Souza MM, Cechinel-Filho V, Bresolin TMB. Aleurites moluccana (L.) Willd. leaves: mechanical antinociceptive properties of a standardized dried extract and its chemical markers. Evid Based Complement Alternat Med 2011; 2011: 1-10
    CrossrefPubMedGoogle Scholar
  • 7 Quintão NL, Antonialli CS, da Silva GF, Rocha LW, de Souza MM, Malheiros A, Meyre-Silva C, Lucinda-Silva RM, Bresolin TM, Filho VC. Aleurites moluccana and its main active ingredient, the flavonoid 2″-O-rhamnosylswertisin, have promising antinociceptive effects in experimental models of hypersensitivity in mice. Pharmacol Biochem Behav 2012; 102: 302-311
    CrossrefPubMedGoogle Scholar
  • 8 Quintão NLM, Pastor MVD, Antonialli CS, da Silva GF, Rocha LW, Berté TE, de Souza MM, Meyre-Silva C, Lucinda-Silva RM, Bresolin TMB, Cechinel-Filho V. Aleurites moluccanus and its main active constituent, the flavonoid 2″-O-rhamnosylswertisin, in experimental model of rheumatoid arthritis. J Ethnopharmacol 2019; 235: 248-254
    CrossrefPubMedGoogle Scholar
  • 9 Meyre-Silva C, More TC, Yunes RA, Santos ARS, Dal-Magro J, Delle-Monache F, Cechinel-Filho V. A triterpene and a flavonoid C-glycoside from Aleurites moluccana L. Willd. (Euphorbiaceae). Acta Farmacéutica Bonaerense 1997; 16: 169-172
    PubMedGoogle Scholar
  • 10 Meyre-Silva C, Yunes RA, Santos ARS, Dal-Magro J, Delle-Monache F, Cechinel-Filho V. Isolation of a C-glycoside flavonoid with antinociceptive action from Aleurites moluccana leaves. Planta Med 1999; 65: 293-294
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Otuki MF, Ferreira J, Lima EV, Meyre-Silva C, Malheiros A, Muller LA, Cani GS, Santos ARS, Yunes RA, Calixto JB. Antinociceptive properties of mixture of α-amyrin and β-amyrin triterpenes: evidence for participation of protein kinase C and protein kinase A pathways. J Pharmacol Exp Ther 2005; 313: 310-318
    CrossrefPubMedGoogle Scholar
  • 12 Quintão NLM, Rocha LW, Silva GF, Reichert S, Claudino VD, Lucinda-Silva RM, Malheiros A, De Souza MM, Cechinel-Filho V, Bresolin TMB, Machado MS, Wagner TM, Meyre-Silva C. Contribution of α,β-amyrenone to the anti-inflammatory and antihypersensitivity effects of Aleurites moluccana (L.) Willd. Biomed Res Int 2014; 2014: 1-12
    CrossrefPubMedGoogle Scholar
  • 13 Silva DB, Fernandes EFA, Ferreira LS, Callejon DR, Guaratini T, Lopes JNC, Meyre-Silva C, Cechinel-Filho V, Lopes NP. Megastigmanes from Aleurites moluccana (L.) Willd. (Euphorbiaceae). Biochem Syst Ecol 2012; 40: 34-37
    CrossrefPubMedGoogle Scholar
  • 14 Liu H, Di Y, Yang J, Teng F, Lu Y, Ni W, Chen C, Hao X. Three novel 3,4-seco-podocarpane trinorditerpenoids from A. moluccana . Tetrahedron Lett 2008; 49: 5150-5151
    CrossrefPubMedGoogle Scholar
  • 15 Alimboyogue AB, Kathlia ACC, Chien-Chang S, Weantai L, Consolacion YR. Chemical constituents of the barks of Aleurites moluccana L. Willd. J Chem Pharmac Res 2014; 6: 1318-1320
    PubMedGoogle Scholar
  • 16 Cesca TG, Faqueti LG, Rocha LW, Meira NA, Meyre-Silva C, de Souza MM, Quintão NLM, Silva RML, Cechinel-Filho V, Bresolin TMB. Antinociceptive, anti-inflammatory, and wound healing features in animal models treated with a semisolid herbal medicine based on Aleurites moluccana L. Willd. Euforbiaceae standardized leaf extract semisolid herbal. J Ethnopharmacol 2012; 143: 355-362
    CrossrefPubMedGoogle Scholar
  • 17 MacDonald R, Camargo SS, Meyre-Silva C, Quintão NLM, Cechinel-Filho V, Bresolin TMB, Lucinda-Silva RM. Development of an oral suspension containing dry extract of Aleurites moluccanus with anti-inflammatory activity. Rev Bras Farmacog 2016; 26: 68-76
    CrossrefPubMedGoogle Scholar
  • 18 Cechinel-Filho V, Bresolin TMB, Bittencourt CMS, Sousa MM, Lucinda-Silva RM, Quintão NLM, Mora TC, Picolli C, Pereira MC, Nita ME, Spricigo R. Processo de obtenção de um extrato padronizado estável e seu uso. INPI PI 0804525-9; 2021.
    Google Scholar
  • 19 Matsuda M, Huh Y, Ji RR. Roles in inflammation, neurogenic inflammation, and neuroinflammation in pain. J Anesth 2019; 33: 131-139
    CrossrefPubMedGoogle Scholar
  • 20 Theken KN. Variability in analgesic response to non-steroidal anti-inflammatory drugs. Prostaglandins Other Lipid Mediat 2018; 139: 63-70
    CrossrefPubMedGoogle Scholar
  • 21 Dona I, Salas M, Perkins JR, Barrionuevo E, Gaeta F, Cornejo-Garcia JÁ, Campo P, Torres MJ. Hypersensitivity reactions to non-steroidal anti-inflammatory drug. Curr Pharm Des 2016; 22: 6784-6802
    CrossrefPubMedGoogle Scholar
  • 22 Yatoo MI, Gopalakrishnan A, Saxena A, Parray OR, Tufani NA, Chakraborty S, Tiwari R, Dhama K, Iqbal HMN. Anti-inflammatory drugs and herbs with special emphasis on herbal medicines for countering inflammatory diseases and disorders–a review. Recent Pat Inflamm Allergy Drug Discov 2018; 2: 39-58
    CrossrefPubMedGoogle Scholar
  • 23 Azab A, Nassar A, Azab AN. Anti-inflammatory activity of natural products. Molecules 2016; 21: 1321
    CrossrefPubMedGoogle Scholar
  • 24 Carvalho AMS, Heimfarth L, Santos KA, Guimarães AG, Picot L, Almeida JRGS, Quintans JSS, Quintas-Junior LJ. Terpenes as possible drugs for the mitigation of arthritic symptoms–a systematic review. Phytomedicine 2019; 57: 137-147
    CrossrefPubMedGoogle Scholar
  • 25 Barreto MB, Gomes CL, De-Freitas JVB, Pinto FCL, Silveira ER, Gramosa NV, Torres DSC. Flavonoids and terpenoids from Croton muscicarpa (Euphorbiaceae). Quim Nova 2013; 36: 675-679
    CrossrefPubMedGoogle Scholar
  • 26 Lima GS. Estudo da atividade tripannossomicida e leishmanicida de extrato, frações e terpenos de Croton cajucara Benth (These). Rio de Janeiro: Universidade federal rural do Rio de Janeiro; 2014
    Google Scholar
  • 27 Mavar-Manga H, Haddad M, Pieters L, Baccelli C, Penge A, Quetin-Leclercq J. Anti-inflammatory compounds from leaves and root bark of Alchornea cardifolia (Schumach. & Thonn.) Müll. Arg. J Ethnopharmacol 2008; 115: 25-29
    CrossrefPubMedGoogle Scholar
  • 28 Perazzo FF, Carvalho JCT, Rodrigues M, Morais EKL, Maciel MAM. Comparative anti-inflammatory and antinociceptive effects of terpenoids and an aqueous extract obtained from Croton cajucara Benth. Rev Bras Farmacog 2007; 7: 521-528
    CrossrefPubMedGoogle Scholar
  • 29 Cooke RG, Down JG. Colouring matters of Australian plants XVI. Minor constituents of Dianella revoluta and Stypandra grandis . Aust J Chem 1971; 24: 1257-1265
    CrossrefPubMedGoogle Scholar
  • 30 Mun SK, Kang KY, Jang HY, Hwang YH, Hong SG, Kim SJ, Cho HW, Chang DJ, Hur JS, Yee ST. Atraric acid exhibits anti-inflammatory effect in lipopolysaccharide-stimulated RAW264.7 cells and mouse models. Int J Molec Sci 2020; 21: 1-13
    PubMedGoogle Scholar
  • 31 Maslovskaya L, Asavchenko AI, Gordon VA, Reddell PW, Pierce CJ, Parsons PG, Williams CM. Isolation and confirmation of the proposed cleistanthol biogentic link from Croton insularis. Org Lett 2011; 3: 1032-1035
    CrossrefPubMedGoogle Scholar
  • 32 Liu H, Li S, Zhao Y, Hao X, Li J, Hua Y, Xie B, Ging C, Chen C. Four new podocarpane-type trinoditerpenes from A. moluccana . Helv Chim Acta 2007; 90: 2017-2023
    CrossrefPubMedGoogle Scholar
  • 33 Posadas I, Bucci M, Roviezzo F, Rossi A, Parente L, Sautebin L, Cirino G. Carrageenan-induced mouse paw oedema is biphasic, age-weight dependent and displays differential nitric oxide cyclooxygenase-2 expression. Br J Pharmacol 2004; 142: 331-338
    CrossrefPubMedGoogle Scholar
  • 34 Kalpesh RP, Umesh BM, Banappa SU, Sameer NG, Sateesh B, Sanjay JS, Shreesh O, Chandragouda RP. Animal models of inflammation for screening of anti-inflammatory drugs: implications for the discovery and development of phytopharmaceuticals. Int J Mol Sci 2019; 20: 4367
    Google Scholar
  • 35 Ricciotti E, Fitzgerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 2011; 31: 986-1000
    CrossrefPubMedGoogle Scholar
  • 36 Robb CT, Mcsorley HJ, Lee J, Aoki T, Yu C, Crittenders S, Astier A, Felton JM, Parkinson N, Ayele A, Breyer RM, Anderton SM, Narumiya S, Rossi AG, Howie SE, Guttman-Yassky E, Weller RB, Yao C. Prostaglandin E2 stimulates adaptive IL-22 production and promotes allergic contact dermatitis. J Allergy Clin Immunol 2018; 141: 152-162
    CrossrefPubMedGoogle Scholar
  • 37 Chengcan Y, Narumiya S. Prostaglandin-cytokine crosstalk in chronic inflammation. Br J Pharmacol 2019; 176: 337-354
    CrossrefPubMedGoogle Scholar
  • 38 Rea IM, Gibson DS, Mcgilligan V, Mcnerlan SE, Alexander HD, Ross OA. Age and age-related diseases: role of inflammation triggers and cytokines. Front Immunol 2018; 9: 86
    CrossrefPubMedGoogle Scholar
  • 39 Fernández-Ruiz M, Aguado JM. Risk of infection associated with anti-TNF-alpha therapy. Expert Rev Anti Infect Ther 2018; 16: 939-956
    CrossrefPubMedGoogle Scholar
  • 40 Cunha TM, Verri-Junior WA, Silva JS, Poole S, Cunha FQ, Ferreira SH. A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proc Natl Acad Sci U S A 2005; 102: 1755-1760
    CrossrefPubMedGoogle Scholar
  • 41 Quintão NL, Rocha LW, Silva GF, Reichert S, Claudino VD, Lucinda-Silva RM, Malheiros A, de Souza MM, Cechinel Filho V, Bresolin TMB, da Silva Machado M, Wagner TM, Meyre-Silva C. Contribution of α,β-Amyrenone to the anti-Inflammatory and antihypersensitivity effects of Aleurites moluccana (L.) Willd. Biomed Res Int 2014; 2014: 1-11
    CrossrefPubMedGoogle Scholar
  • 42 Araújo-Junior VT, Silva MS, da Cunha EVL, Agra MF, Silva-Filho RN, Barbosa-Filho JM, Braz-Filho R. Alkaloids and diterpenes from Croton moritibensis . Pharmac Biol 2004; 42: 62-67
    CrossrefPubMedGoogle Scholar
  • 43 Quintão NLM, Medeiros R, Santos ARS, Campos MM, Calixto JB. Effects of diacerhein on mechanical allodynia in inflammatory and neuropathic models of nociception in mice. Anesth Anal 2005; 101: 1763-1769
    CrossrefPubMedGoogle Scholar
  • 44 Kassuya CA, Ferreira J, Claudino RF, Calixto JB. Intraplantar PGE2 causes nociceptive behaviour and mechanical allodynia: the role of prostanoid E receptors and protein kinases. Br J Pharmacol 2007; 150: 727-737
    CrossrefPubMedGoogle Scholar
  • 45 Khasar SG, Dina OA, Green PG, Levine JD. Estrogen regulates adrenal medullary function producing sexual dimorphism in nociceptive threshold and beta-adrenergic receptor-mediated hyperalgesia in the rat. Eur J Neurosci 2005; 21: 3379-3386
    CrossrefPubMedGoogle Scholar