Abstract
Cuphea aequipetala Cav (Lythraceae) is an herb used in folk treatment for pain and inflammation. The aim of this study was to evaluate the antinociceptive and anti-inflammatory actions of an ethanol extract from the leaves and stem of Cuphea aequipetala (CAE). The antinociceptive actions of CAE (10–200 mg/kg p.o.) were assessed with the acetic acid-induced writhing, hot plate, and formalin tests. The possible mechanism of action of CAE was evaluated using inhibitors. The effects of CAE on motor coordination were assessed by the rotarod test. The in vitro anti-inflammatory actions of CAE were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed by the TPA-induced ear oedema and the carrageenan-induced paw oedema tests. The production of inflammatory mediators was estimated from both in vitro and in vivo assays. CAE showed antinociception (ED50 = 90 mg/kg) in the acetic acid test and in the second phase of the formalin test (ED50 = 158 mg/kg). Pretreatment with glibenclamide or L-NAME partially reversed the antinociception shown by the plant extract. CAE (50–200 mg/kg) did not affect motor coordination in mice. CAE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 10 pg/ml) and, in the carrageenan-induced paw oedema test (threefold increase). In conclusion, CAE induced antinociceptive effects without affecting motor coordination, probably due to the involvement of nitric oxide and ATP-sensitive K+ channels. CAE also exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.
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References
Aguilar-Rodríguez S, Echeveste-Ramírez NL, López-Villafranco ME, Aguilar-Contreras A, Vega-Ávila E, Reyes-Chilpa R (2012) Ethnobotany, analytical micrograph of leaves and stems and phytochemistry of Cuphea aequipetala Cav. (Lythraceae): a contribution to the herbal pharmacopoeia of the United Mexican States (FHEUM). Bol Latinoam Caribe Plant Med Aromat 11(4):316–330
Alonso-Castro AJ, Domínguez F, Zapata-Morales JR, Carranza-Álvarez C (2015) Plants used in the traditional medicine of Mesoamerica (Mexico and Central America) and the Caribbean for the treatment of obesity. J Ethnopharmacol 175:335–345
Arana-Argáez VE, Chan-Zapata I, Canul-Canche J, Fernández-Martín K, Martín-Quintal Z, Torres-Romero JC, Coral-Martínez TI, Lara-Riegos JC, Ramírez-Camacho MA (2017) Immunosuppresive effects of the methanolic extract of Chrysophyllum cainito leaves on macrophage functions. Afr J Tradit Complement Altern Med 14(1):179–186
Barton GM (2008) A calculated response: control of inflammation by the innate immune system. J Clin Investig 118:413–420
BenSaad LA, Kim KH, Quah CC, Kim WR, Shahimi M (2017) Anti-inflammatory potential of ellagic acid, gallic acid and Punicalagin A&B isolated from Punica granatum. BMC Complement Altern Med 17(1):47
Carbone L (2011) Pain in laboratory animals: the ethical and regulatory imperatives. PLoS One 6(9):e21578
Carter RB (1991) Differentiating analgesic and non-analgesic drug activities on rat hot plate: effect of behavioral endpoint. Pain 47(2):211–220
Chernov HI, Wilson DE, Fowler F, Plummer AJ (1967) Non-specificity of the mouse writhing test. Arch Int Pharmacodyn Ther 167:171–178
Duque GA, Descoteaux A (2014) Macrophage cytokines: involvement in immunity and infectious diseases. Front Immunol 5:491
Fernandes ER, Santos AL, Arruda AM, Vasques-Pinto LD, Godinho RO, Torres LM, Lapa AJ, Souccar C (2002) Antinociceptive and anti-inflammatory activities of the aqueous extract and isolated Cuphea carthagenensis (Jacq.) JF Macbr. Rev Bras Farmacogn 12:55–56
Flamand N, Mancuso P, Serezani CH, Brock TG (2007) Leukotrienes: mediators that have been typecast as villains. Cell Mol Life Sci 64(19–20):2657–2670
Garcia-Lara B, Enciso-Donis I, Wrobel K, Wrobel K (2018) Determination of six priority phthalates and di(ethylhexyl) adipate in maize tortilla by gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode. J Mex Chem Soc 62(2):270–281
Gyires K, Torma Z (1984) The use of the writhing test in mice for screening different types of analgesics. Arch Int Pharmacodyn Ther 267(1):131–140
Kelly A, Lynch A, Vereker E, Nolan Y, Queenan P, Whittaker E, O'Neill LA, Lynch MA (2001) The anti-inflammatory cytokine, interleukin (IL)-10, blocks the inhibitory effect of IL-1 beta on long term potentiation. A role for jnk. J Biol Chem 276(49):45564–45572
Kroes BH, van den Berg AJJ, Quarles van Ufford HC, van Dijk H, Labadie RP (1992) Anti-inflammatory activity of gallic acid. Planta Med 58(6):499–504
Liu KYP, Hu S, Chan BCL, Wat ECL, Lau CBS, Hon KL, Fung KP, Leung PC, Hui PCL, Lam CWK, Wong CK (2013) Anti-inflammatory and anti-allergic activities of Pentaherb Formula, Moutan Cortex (Danpi) and gallic acid. Molecules 18(3):2483–2500
Malmberg AB, Yaksh TL (1992) Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. J Pharmacol Exp Ther 263(1):136–146
Martínez-Bonfil BP, Pineda-Montero M, López-Laredo AR, Salcedo-Morales G, Evangelista-Lozano S, Trejo-Tapia G (2013) A propagation procedure for Cuphea aequipetala Cav. (Lythraceae) and antioxidant properties of wild and greenhouse-grown plants. Bol Latinoam Caribe Plant Med Aromat 12(1):1–14
Murakawa M, Yamaoka K, Tanaka Y, Fukuda Y (2006) Involvement of tumor necrosis factor (TNF)-alpha in phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin oedema in mice. Biochem Pharmacol 71(9):1331–1336
Murray CW, Porreca F, Cowan A (1988) Methodological refinements to the mouse paw formalin test. An animal model of tonic pain. J Pharmacol Methods 20(2):175–186
Palacios-Espinosa JF, Arroyo-García O, García-Valencia G, Linares E, Bye R, Romero I (2014) Evidence of the anti-Helicobacter pylori, gastroprotective and anti-inflammatory activities of Cuphea aequipetala infusion. J Ethnopharmacol 151(2):990–998
Pick E, Keisari Y (1980) A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Methods 38(1–2):161–170
Ramírez-Atehortúa AM, Morales-Agudelo L, Osorio E, Lara-Guzmán OJ (2018) The traditional medicinal plants Cuphea calophylla, Tibouchina kingii, and Pseudelephantopus spiralis attenuate inflammatory and oxidative mediators. Evid Based Complement Alternat Med 2018 (Article id 1953726)
Santos AR, De Campos RO, Miguel OG, Cechinel-Filho V, Yunes RA, Calixto JB (1999) The involvement of K+ channels and Gi/o protein in the antinociceptive action of the gallic acid ethyl ester. Eur J Pharmacol 379(1):7–17
Santos FA, Jeferson FA, Santos CC, Silveira ER, Rao VSN (2005) Antinociceptive effect of leaf essential oil from Croton sonderianus in mice. Life Sci 77(23):2953–2963
Santucci L, Fiorucci S, Chiorean M, Brunori PM, Di Matteo FM, Sidoni A, Migliorati G, Morelli A (1996) Interleukin 10 reduces lethality and hepatic injury induced by lipopolysaccharide in galactosamine-sensitized mice. Gastroenterol 111(3):736–744
Sugishita E, Amagaya S, Ogihara V (1981) Antiinflammatory testing methods comparative evaluation of mice and rats. J Pharm Dyn 4(8):565–575
Trushin SA, Pennington KN, Carmona EM, Asin S, Savoy DN, Billadeau DD, Paya CV (2003) Protein kinase calpha (PKCalpha) acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T lymphocytes. Mol Cell Biol 23(19):7068–7081
Tsuda M, Suzuki T, Misawa M, Nagase H (1996) Involvement of the opioid system in the anxiolytic effect of diazepam in mice. Eur J Pharmacol 307(1):7–14
Uscanga-Palomeque AC, Zapata-Benavides P, Saavedra-Alonso S, Zamora-Ávila DE, Franco-Molina MA, Arellano-Rodríguez M, Manilla-Muñoz E, Martínez-Torres AC, Trejo-Ávila LM, Rodríguez-Padilla C (2019) Inhibitory effect of Cuphea aequipetala extracts on murine B16F10 melanoma in vitro and in vivo. Biomed Res Int 2019 (Article id:8560527)
Vega-Avila E, Aguilar RT, Estrada MJ, Ortega MLV, Ramos RR (2004) Cytotoxic activity of Cuphea aequipetala. Proc West Pharmacol Soc 47:129–133
Villa-Ruano N, Zurita-Vásquez GG, Pacheco-Hernández Y, Betancourt-Jiménez MG, Cruz-Durán R, Duque-Bautista H (2013) Anti-lipase and antioxidant properties of 30 medicinal plants used in Oaxaca. México Biol Res 46(2):153–160
Waizel-Bucay J, Martinez-Porcayo G, Villarreal-Ortega ML, Alonso-Cortes D, Pliego-Castañeda A (2003) Estudio preliminar etnobotánico, fitoquímico de la actividad citotóxica y antimicrobiana de Cuphea aequipetala Cav. (Lythraceae). Polibotánica 15:99–108
Zhu L, Gu PQ, Shen H (2019) Gallic acid improved inflammation via NF-κB pathway in TNBS-induced ulcerative colitis. Int Immunopharmacol 67:129–137
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Alonso-Castro, A.J., Arana-Argáez, V., Yáñez-Barrientos, E. et al. Antinociceptive and anti-inflammatory effects of Cuphea aequipetala Cav (Lythraceae). Inflammopharmacol 29, 295–306 (2021). https://doi.org/10.1007/s10787-020-00709-3
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DOI: https://doi.org/10.1007/s10787-020-00709-3