{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:25:41Z","timestamp":1788423941085,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T00:00:00Z","timestamp":1328140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sabicea species are used in the Amazon for treatment of fever and malaria, which suggests that its chemical constituents may have some effect on pain and inflammation. Phytochemical analysis of the hexane fraction obtained from the crude ethanol extract from Sabicea grisea var. grisea Cham. &amp; Schltdl (Rubiaceae), an endemic plant in Brazil, resulted in the isolation of octacosanol. This study investigated the antinociceptive and anti-inflammatory effects of the octacosanol in different experimental models. The crude ethanolic extract and hexane fraction obtained from the leaves of S. grisea produced an inhibition of acetic acid-induced pain. Moreover, octacosanol isolated from the hexane fraction produced a significant inhibition of pain response elicited by acetic acid. Pre-treatment with yohimbine, an alpha 2-adrenergic receptor antagonist, notably reversed the antinociceptive activity induced by octacosanol in the abdominal constriction test. Furthermore, mice treated with octacosanol did not exhibit any behavioral alteration during the hot plate and rota-rod tests, indicating non-participation of the supraspinal components in the modulation of pain by octacosanol with no motor abnormality. In the formalin test, octacosanol did not inhibit the licking time in first phase (neurogenic pain), but significantly inhibited the licking time in second phase (inflammatory pain) of mice. The anti-inflammatory effect of octacosanol was evaluated using carrageenan-induced pleurisy. The octacosanol significantly reduced the total leukocyte count and neutrophils influx, as well as TNF-\u03b1 levels in the carrageenan-induced pleurisy. This study revealed that the mechanism responsible for the antinociceptive and anti-inflammatory effects of the octacosanol appears to be partly associated with an inhibition of alpha 2-adrenergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, these results demonstrated that the octacosanol from the leaves of S. grisea possesses antinociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes.<\/jats:p>","DOI":"10.3390\/ijms13021598","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T11:13:56Z","timestamp":1328181236000},"page":"1598-1611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Antinociceptive and Anti-Inflammatory Effects of Octacosanol from the Leaves of Sabicea grisea var. grisea in Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Anderson Marques de","family":"Oliveira","sequence":"first","affiliation":[{"name":"Instituto de Qu\u00edmica e Biotecnologia, Universidade Federal de Alagoas, Macei\u00f3\/AL 57072-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia M.","family":"Conserva","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica e Biotecnologia, Universidade Federal de Alagoas, Macei\u00f3\/AL 57072-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamylle N.","family":"De Souza Ferro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Universidade Federal de Alagoas, Macei\u00f3\/AL 57072-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fab\u00edola de Almeida","family":"Brito","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Universidade Federal de Alagoas, Macei\u00f3\/AL 57072-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ros\u00e2ngela P. Lyra","family":"Lemos","sequence":"additional","affiliation":[{"name":"Instituto do Meio Ambiente do Estado de Alagoas, Macei\u00f3\/AL 57017-320, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Barreto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Celular, Universidade Federal de Alagoas, Macei\u00f3\/AL 57072-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2012,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1021\/jf050508r","article-title":"Policosanol contents and compositions of wheat varieties","volume":"53","author":"Irmak","year":"2005","journal-title":"J. Agric. Food Chem"},{"key":"ref_2","first-page":"81","article-title":"Octacosanol ingestion and its effects on metabolic responses to submaximal cycle ergometry, reaction time and chest and grip strength","volume":"1","year":"1986","journal-title":"Int. Clin. Nutr. Rev"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/aps.2010.69","article-title":"Protective effects of octacosanol on 6-hydroxydopamine-induced Parkinsonism in rats via regulation of ProNGF and NGF signaling","volume":"31","author":"Wang","year":"2010","journal-title":"Acta Pharmacol. Sin"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.ejphar.2008.04.027","article-title":"Octacosanol isolated from Tinospora cordifolia downregulates VEGF gene expression by inhibiting nuclear translocation of NF-<kappa>B and its DNA binding activity","volume":"588","author":"Thippeswamy","year":"2008","journal-title":"Eur. J. Pharmacol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s11745-009-3338-y","article-title":"Regulation of HMGCoA reductase activity by policosanol and octacosadienol, a new synthetic analogue of octacosanol","volume":"44","author":"Mantegna","year":"2009","journal-title":"Lipids"},{"key":"ref_6","first-page":"205","article-title":"Cholesterol-lowering effects of policosanol in rabbits","volume":"27","author":"Arruzazabala","year":"1994","journal-title":"Biol. Res"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1124\/jpet.106.107144","article-title":"Policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP-kinase","volume":"318","author":"Singh","year":"2006","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1046\/j.1440-1681.2002.03746.x","article-title":"Antiplatelet effects of policosanol (20 and 40 mg\/day) in healthy volunteers and dyslipidaemic patients","volume":"29","author":"Arruzazabala","year":"2002","journal-title":"Clin. Exp. Pharmacol. Physiol"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0049-3848(93)90030-R","article-title":"Effects of Policosanol on platelet aggregation in rats","volume":"69","author":"Arruzazabala","year":"1993","journal-title":"Thromb. Res"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/j.2042-7158.1995.tb06732.x","article-title":"Anti-ulcer activity of higher primary alcohols of beeswax","volume":"47","author":"Carbajal","year":"1995","journal-title":"J. Pharm. Pharmacol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jnutbio.2008.01.007","article-title":"Long-chain fatty alcohols from pomace olive oil modulate the release of proinflammatory mediators","volume":"20","author":"Perona","year":"2009","journal-title":"J. Nutr. Biochem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s11418-010-0496-4","article-title":"Evaluation of anti-inflammatory and antinociceptive effects of D-002 (beeswax alcohols)","volume":"65","author":"Ravelo","year":"2011","journal-title":"J. Nat. Med"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jep.2009.06.034","article-title":"Ethnopharmacology of Q\u2019eqchi\u2019 Maya antiepileptic and anxiolytic plants: Effects on the GABAergic system","volume":"125","author":"Awad","year":"2009","journal-title":"J. Ethnopharmacol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3942","DOI":"10.3390\/ijms11103942","article-title":"Pharmacological proprieties of the ethanol extract of Muehlenbeckia platyclada (F. Muell.) Meisn. leaves","volume":"11","author":"Fagundes","year":"2010","journal-title":"Int. J. Mol. Sci"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.3390\/ijms11052067","article-title":"Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal models","volume":"11","author":"Vieira","year":"2010","journal-title":"Int. J. Mol. Sci"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3923\/pjbs.2011.149.169","article-title":"Sub-Saharan Rubiaceae: A review of their traditional uses, phytochemistry and biological activities","volume":"14","author":"Karou","year":"2011","journal-title":"Pak. J. Biol.Sci"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.phytochem.2004.12.021","article-title":"Chemotaxonomy of the Rubiaceae family based on leaf fatty acid composition","volume":"66","author":"Mongrand","year":"2005","journal-title":"Phytochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1021\/np020547m","article-title":"Turbinatine, a potential key intermediate in the biosynthesis of corynanthean-type indole alkaloids","volume":"66","author":"Cardoso","year":"2003","journal-title":"J. Nat. Prod"},{"key":"ref_19","first-page":"237","article-title":"Secondary metabolites from Asperula lutea subsp. rigidula","volume":"6","author":"Tzakou","year":"2011","journal-title":"Nat. Prod. Commun"},{"key":"ref_20","first-page":"7","article-title":"Sabiceeae and Virectarieae (Rubiaceae, Ixoroideae): One or two tribes? New tribal and generic circumscriptions of Sabiceeae and biogeography of Sabicea s.l","volume":"57","author":"Khan","year":"2008","journal-title":"Taxon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jep.2009.09.024","article-title":"The rainbow hurts my skin: medicinal concepts and plants uses among the Yanesha (Amuesha), an Amazonian Peruvian ethnic group","volume":"127","author":"Valadeau","year":"2010","journal-title":"J. Ethnopharmacol"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jep.2007.04.009","article-title":"Amazonian plants from Peru used by Quechua and Mestizo to treat malaria with evaluation of their activity","volume":"112","author":"Roumy","year":"2007","journal-title":"J. Ethnopharmacol"},{"key":"ref_23","first-page":"295","article-title":"Abdominal constriction response and its suppression by analgesic drugs in mouse","volume":"32","author":"Collier","year":"1968","journal-title":"Br. J. Pharmacol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0014-2999(99)00790-6","article-title":"Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice","volume":"387","author":"Ribeiro","year":"2000","journal-title":"Eur. J. Pharmacol"},{"key":"ref_25","first-page":"103","article-title":"Gangliosides antinociceptive effects in rodents","volume":"272","author":"Caruso","year":"1984","journal-title":"Arch. Int. Pharmacodyn. Ther"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1399-6576.1997.tb04623.x","article-title":"Pharmacology and mechanisms of opioid analgesic activity","volume":"41","author":"Yaksh","year":"1997","journal-title":"Acta Anaesthesiol. Scand"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-3565(25)21463-X","article-title":"In vivo studies on spinal opiate receptor systems mediating antinociception. II. Pharmacological profiles suggesting a differential association of mu, delta and kappa receptors with visceral chemical and cutaneous thermal stimuli in the rat","volume":"228","author":"Schmauss","year":"1984","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S0022-3565(25)20891-6","article-title":"Pharmacological analysis of alpha-2 adrenergic mechanisms in nociception and ataxia","volume":"232","author":"Luttinger","year":"1985","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0022-3565(25)38297-2","article-title":"Characterization of the antinociception produced by intrathecally administered muscarinic agonists in rats","volume":"266","author":"Iwamoto","year":"1993","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0031-6997(24)01514-X","article-title":"Animal models of nociception","volume":"53","author":"Gozariu","year":"2001","journal-title":"Pharmacol. Rev"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/jps.3030460322","article-title":"A note on a simple apparatus for detecting neurological deficit in rats and mice","volume":"46","author":"Dunham","year":"1957","journal-title":"J. Am. Pharm. Assoc"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13525","DOI":"10.1073\/pnas.0705924104","article-title":"TRPA1 mediates formalin-induced pain","volume":"104","author":"McNamara","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0304-3959(92)90003-T","article-title":"The formalin test: An evaluation of the method","volume":"51","author":"Tjolsen","year":"1992","journal-title":"Pain"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0160-5402(88)90078-2","article-title":"Methodological refinements to the mouse paw formalin test. An animal model of tonic pain","volume":"20","author":"Murray","year":"1988","journal-title":"J. Pharmacol. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Farias, J.A., Ferro, J.N., Silva, J.P., Agra, I.K., Oliveira, F.M., Candea, A.L., Conte, F.P., Ferraris, F.K., Henriques, M.D., and Conserva, L.M. (2011). Modulation of inflammatory processes by leaves extract from Clusia nemorosa both in vitro and in vivo animal models. Inflammation.","DOI":"10.1007\/s10753-011-9372-y"},{"key":"ref_36","first-page":"123","article-title":"Pleural models of inflammation: immune and nonimmune","volume":"225","author":"Moore","year":"2003","journal-title":"Methods Mol. Biol"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0952-3278(98)90135-1","article-title":"Anti-inflammatory activity of D-002: An active product isolated from beeswax","volume":"59","author":"Carbajal","year":"1998","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1046\/j.1365-2222.2003.01575.x","article-title":"Suppression of allergic reaction by lambda-carrageenan: toll-like receptor 4\/MyD88-dependent and -independent modulation of immunity","volume":"33","author":"Tsuji","year":"2003","journal-title":"Clin. Exp. Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1006\/cyto.1998.0376","article-title":"Generation of inflammatory cytokines in zymosan-induced pleurisy in rats: TNF induces IL-6 and cytokine-induced neutrophil chemoattractant (CINC) in vivo","volume":"10","author":"Utsunomiya","year":"1998","journal-title":"Cytokine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ejphar.2006.06.001","article-title":"N-hexacosanol ameliorates streptozotocin-induced diabetic rat nephropathy","volume":"544","author":"Saito","year":"2006","journal-title":"Eur. J. Pharmacol"},{"key":"ref_41","first-page":"46","article-title":"Chemical investigation of Tinospora cordifolia","volume":"34","author":"Dixit","year":"1971","journal-title":"Ind. J. Appl. Chem"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1023\/A:1005499907009","article-title":"Identification of 1-octacosanal and 6-methoxy-2- benzoxazolinone from wheat as ovipositional stimulants for Hessian fly, Mayetiola destructor","volume":"26","author":"Morris","year":"2000","journal-title":"J. Chem. Ecol"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.arcmed.2004.12.006","article-title":"In vitro and in vivo study of octacosanol metabolism","volume":"36","author":"Menendez","year":"2005","journal-title":"Arch. Med. Res"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0022-3565(25)05180-8","article-title":"Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines","volume":"107","author":"Eddy","year":"1953","journal-title":"J. Pharmacol. Exp. Ther"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/2\/1598\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:48:43Z","timestamp":1760219323000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/13\/2\/1598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,2]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2012,2]]}},"alternative-id":["ijms13021598"],"URL":"https:\/\/doi.org\/10.3390\/ijms13021598","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,2]]}}}