Attenuation of pain and inflammation induced in mice treated orally with crude extract of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae)

Mariela Ortiz Isabelle Wilson Yenny Montalbetti Olga Heinichen Wilfrido Arrúa Nelson Alvarenga Derlis A. Ibarrola María del Carmen Hellión-Ibarrola   

Open Access   

Published:  Jun 14, 2022


The objective of this work was to determine the analgesic and anti-inflammatory activity of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in experimental models of acute pain and inflammation in mice. Methods of pain induced by caudal pressure (Randall-Selitto), chemical stimulation (acetic acid or the writhing test), and thermal stimulation (hot plate) were used to study analgesic effects. Additionally, edema of the paw induced by injection of 1% carrageenan was used to evaluate the anti-edema activity of A. polystachya. Oral doses of 100 and 200 mg/kg of crude extract of A. polystachya (CEAp) significantly reduced the sensibility to painful stimuli induced by the application of pressure in the tail comparable with an analgesic effect (p < 0.05) in a non-dose dependent manner. Additionally, the number of abdominal contortions was significantly reduced in comparison with the control group and with similar strength to the group treated with Indomethacin 10.0 mg/kg. Similarly, in the model of pain induced by thermal stimulation, it was observed that the groups treated with CEAp presented statistically significant analgesic activity in comparison with the control group and with a similar intensity to the group treated with morphine 6.0 mg/kg. Finally, a statistically significant reduction of edema induced by 1% carrageenan was observed with oral administration of 100 mg/kg of CEAp in comparison to the positive control of edema in a manner similar to the group treated with Indomethacin 10 mg/kg. Based on these results, it was concluded that the CEAp possesses the capacity to increase pain threshold in three pre-clinical models of pain induced (mechanical pressure, chemically and thermally) in mice, compatible with an analgesic effect. Also, CEAp demonstrated antiedematous capacity in carrageenan-induced paw edema in mice, concordant with anti-inflammatory effect using the plethysmography method. These pharmacological effects are potentially due to the presence of verbascoside in CEAp. Additionally, these experimental results are correlated with the popular use of CEAp and present a variety of opportunities for pharmaceutical research such as the development of innovative phytopharmaceuticals.

Keyword:     Aloysia polystachya analgesia Randall-Selitto abdominal contortions hot plate plethysmometer.


Ortiz MA, Wilson I, Montalbetti Y, Heinichen OY, Arrua W, Ibarrola DA, Hellión-Ibarrola MDC. Attenuation of pain and inflammation induced in mice treated orally with crude extract of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae). J Appl Pharm Sci, 2022. Online First.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text


Bannon AW. 2001. Models of pain: hot-plate and formalin test in rodents. Curr Protoc Pharmacol, 2001; 5.7.1-11.

Bannon AW, Malmberg AB. 2007. Models of nociception: hotplate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci, 2007; 8.9.1-16.

Barroso J, Branco P, Apkarian AV. Brain mechanisms of chronic pain: critical role of translational approach. Transl Res, 2021; 238:1-14.

Carmona F, Coneglian FS, Batista PA, Aragon DC, Angelucci MA, Martinez EZ, Pereira AMS. Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) powdered leaves are effective in treating anxiety symptoms: a phase-2, randomized, placebo-controlled clinical trial. J Ethnopharmacol, 2019; 242:112060.

Carvalho, A.P., Bezerra, M.M., Girão, V.C.C., Cunha, F.Q., Rocha, F.A.C. ANTI-INFLAMMATORY AND ANTI-NOCICEPTIVE ACTIVITY OF RISEDRONATE IN EXPERIMENTAL PAIN MODELS IN RATS AND MICE. Clin. Exp. Pharmacol. Physiol. 2006; 33, 601-606.

Consolini AE, Berardi A, Rosella MA, Volonté MG. Antispasmodic effects of Aloysia polystachya and A. gratissima tinctures and extracts are due to non-competitive inhibition of intestinal contractility induced by acethylcholine and calcium. Rev Bras Farmacogn, 2011; 21:889-900.

Da Silva JB, Temponi Vdos S, Fernandes FV, de Assis Dias Alves G, de Matos DM, Gasparetto CM, Ribeiro A, de Pinho Jde J, Alves MS, de Sousa OV. New approaches to clarify antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves. Int J Mol Sci, 2011; 12:8993-9008.

De Morais Lima GR, de Albuquerque Montenegro C, de Almeida CL, de Athayde-Filho PF, Barbosa-Filho JM, Batista LM. Database survey of anti-inflammatory plants in South America: a review. Int J Mol Sci, 2011; 12:2692-749.

Duarte DB, Vasko MR, Fehrenbacher JC. Models of inflammation: carrageenan air pouch. Curr Protoc Pharmacol, 2016; 5.6.1-9.

Fehrenbacher, J.C., Vasko, M.R., Duarte, D.B., Models of inflammation: Carrageenan- or complete freund's adjuvant (CFA)-induced edema and hypersensitivity in the rat. Curr. Protoc. Pharmacol. 2012; 56, 5.4.1-5.4.7.

Gregory NS, Harris AL, Robinson CR, Dougherty PM, Fuchs PN, Sluka KA. An overview of animal models of pain: disease models and outcome measures. J Pain, 2014; 14:1-26.

Gutiérrez-Rebolledo GA, Garduño-Siciliano L, GarcíaRodríguez RV, Pérez-González MZ, Chávez MI, Bah M, Siordia-Reyes GA, Chamorro-Cevallos GA, Jiménez-Arellanes MA. Anti-inflammatory and toxicological evaluation of Moussonia deppeana (Schldl. & Cham) Hanst and Verbascoside as a main active metabolite. J Ethnopharmacol, 2016; 187:269-80.

Hellión-Ibarrola MC, Ibarrola DA, Montalbetti Y, Kennedy ML, Heinichen O, Campuzano M, Ferro EA, Alvarenga N, Tortoriello J, De Lima TC, Mora S. The antidepressant-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice. Phytomedicine, 2008; 15: 478-83.

Hellión-Ibarrola MC, Ibarrola DA, Montalbetti Y, Kennedy ML, Heinichen O, Campuzano M, Tortoriello J, Fernández S, Wasowski C, Marder M, De Lima TC, Mora S. The anxiolytic-like effects of Aloysia polystachya (Griseb.) Moldenke (Verbenaceae) in mice. J Ethnopharmacol, 2006; 105:400-8.

Kim, H.S., Kwon, O.K., Park, J.W., Jeong, H.G., Oh, S.R., Lee, H.K., Bach, T.T., Hai, D. Van, Ahn, K.S., Anti-inflammatory activities of methanol extract of Mastixia arborea C.B. Clarke as to mouse macrophage and paw edema. Biosci. Biotechnol. Biochem. 2013; 77, 2356-2361.

Kopach O, Viatchenko-Karpinski V, Belan P, Voitenko N. Development of inflammation-induced hyperalgesia and allodynia is associated with the upregulation of extrasynaptic AMPA receptors in tonically firing lamina II dorsal horn neurons. Front Physiol, 2012; 3:1-8.

Lapa AJ, Souccar C, Lima-Landman MT, De Lima TC. Métodos de avaliação da atividade farmacológica de plantas medicinais. Sociedade Brasileira de Plantas Medicinais, Sao Paulo, Brazil, 2002.

Ma KJ, Zhu ZZ, Yu CH, Zhang H, Liu J, Qin LP. Analgesic, anti-inflammatory, and antipyretic activities of the ethanol extract from Desmodium caudatum. Pharm Biol, 2011; 49:403-7.

Maallo AMS, Moulton EA, Sieberg CB, Giddon DB, Borsook D, Holmes SA. A lateralized model of the pain-depression dyad. Neurosci Biobehav Rev, 2021; 127:876-83.

Martínez GJ, Barboza GE. Natural pharmacopoeia used in traditional Toba medicine for the treatment of parasitosis and skin disorders (Central Chaco, Argentina). J Ethnopharmacol, 2010; 132:86-100.

McCarson KE. Models of inflammation: carrageenan- or complete freund's adjuvant (CFA)-induced edema and hypersensitivity in the rat. Curr Protoc Pharmacol, 2015; 70:5.4.1-9.

Mora S, Díaz-Véliz G, Millán R, Lungenstrass H, Quirós S, Coto-Morales T, Hellión-Ibarrola MC. Anxiolytic and antidepressant-like effects of the hydroalcoholic extract from Aloysia polystachya in rats. Pharmacol Biochem Behav, 2005; 82:373-8.

Muhammad N, Saeed M, Gilani SN, Haq I, Khan H. Analgesic and anti-inflammatory profile of n-hexane fraction of Viola betonicifolia. Trop J Pharm Res, 2012; 11:963-9.

Pereira A, Guimarães C, Pereira S, Crevelin E, Pinto G, Morel L, Bertoni B, França S, Taleb-Contini S. Isolation and identification of phenylethanoid gycosides from Aloysia polystachya and its activity as inhibitors of monoamine oxidase-A. Planta Medica Int Open, 2019; 6:e1-6.

Qnais EY, Abu-Dieyeh M, Abdulla FA, Abdalla SS. The antinociceptive and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol extracts. Pharm Biol, 2010; 48:1149-56.

Real Decreto, M. de A.P. y A., Presidencia, C.E.E., 2005. Real decreto 1201/2005. Boe 252, 34367-34391.

Rojas-Corrales MO, Casas J, Moreno-Brea MR, Gibert-Rahola J, Micó JA. Antinociceptive effects of tricyclic antidepressants and their noradrenergic metabolites. Eur Neuropsychopharmacol, 2003; 13:355-63.

Singh N, Bansal Y, Bhandari R, Marwaha L, Singh R, Chopra K, Kuhad A. Resveratrol protects against ICV collagenase-induced neurobehavioral and biochemical deficits. J Inflamm (United Kingdom), 2017; 14:1-15.

Tabor A, Thacker MA, Moseley GL, Kording KP. Pain : a statistical account. Plos Comput Biol, 2017; 13:1-13.

Tenti, M., Raffaeli, W., Gremigni, P., A Narrative Review of the Assessment of Depression in Chronic Pain. Pain Manag. Nurs. 2022; 23, 158-167.

TrivellatoGrassi L, Malheiros A, Meyre-Silva C, Buss Zda S, Monguilhott ED, Fröde TS, da Silva KA, de Souza MM. From popular use to pharmacological validation: a study of the anti-inflammatory, antinociceptive and healing effects of Chenopodium ambrosioides extract. J Ethnopharmacol, 2013; 145:127-38.

Woolf, C.J., What is this thing called pain? J. Clin. Invest. 2010; 120, 3742-3744.

Article Metrics

1 Absract views 0 PDF Downloads 1 Total views

   Abstract      Pdf Download

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required