Peripheral Analgesic and Anti-Inflammatory Effects of Smilax canariensis in an Animal Model

Abstract

Smilax canariensis Brouss. ex Willd. is an endemic plant of the Canary Islands. Its rhizomes, leaves and stems have been traditionally used in Canary folk medicine to treat a wide variety of conditions including pain. Our objective is to investigate the analgesic and anti-inflammatory activities of different extracts of S. canariensis in Swiss mice, using established biological models for pain and inflammation, such as phenylquinone writhing test, formalin test, tail-flick test and mouse paw edema induced by carrageenan. Oral administration of S. canariensis extracts significantly reduce writhing episodes evoked by phenylquinone injection in a dose-dependent manner; and higher doses result in a reduction of pain similar to or higher than that of the reference drug piroxicam (59.56%; p < 0.01). The extracts also cause a marked dose-dependent inhibition of for-malin-induced pain in the second phase but only minimal inhibition of tail-flick behavior, suggesting that S. canariensis is not a centrally acting analgesic. Finally, in the carrageenan-induced hind paw edema model, the extracts show a moderate anti-inflammatory effect, the most active being the ethyl acetate fraction at 200 mg/kg p.o. (33.33%; p < 0.05). Our results suggest that S. canariensis extracts have clear dose-dependent peripheral analgesic effects, which lends support to the traditional use of this medicinal plant to treat pain associated with inflammatory or other processes.

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Dévora, S. , Abdala, S. and Martín-Herrera, D. (2015) Peripheral Analgesic and Anti-Inflammatory Effects of Smilax canariensis in an Animal Model. Pharmacology & Pharmacy, 6, 391-400. doi: 10.4236/pp.2015.68040.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Cope, D.K. and Lariviere, W.R. (2006) Gene Therapy and Chronic Pain. Scientific World Journal, 31, 1066-1074.
http://dx.doi.org/10.1100/tsw.2006.197
[2] Woodcock, J., Witter, J. and Dionne, R.A. (2007) Stimulating the Development of Mechanism-Based, Individualized Pain Therapies. Nature Reviews Drug Discovery, 6, 703-710.
http://dx.doi.org/10.1038/nrd2335
[3] Eming, S.A., Krieg, T. and Davidson, J.M. (2007) Inflammation in Wound Repair: Molecular and Cellular Mechanisms. Journal of Investigative Dermatology, 127, 514-525.
http://dx.doi.org/10.1038/sj.jid.5700701
[4] Reanmongkol, W., Itharat, A. and Bouking, P. (2007) Evaluation of the Anti-Inflammatory, Antinociceptive and Antipyretic Activities of the Extracts from Smilax corbularia Kunth Rhizomes in Mice and Rats (in Vivo). Songklanakarin Journal of Science and Technology, 29, 59-67.
[5] Chanda, S. and Dave, R. (2009) In Vitro Models for Antioxidant Activity Evaluation and Some Medicinal Plants Possessing Antioxidant Properties: An Overview. African Journal of Microbiology Research, 3, 981-996.
[6] Kubo, S., Mimaki, Y., Sashida, Y., Mimaki, Y. and Sashida, Y. (1992) Steroidal Saponins from the Rhizomes of Smilax sieboldii. Phytochemistry, 31, 2445-2450.
http://dx.doi.org/10.1016/0031-9422(92)83296-B
[7] Chen, T., Li, J.X. and Xu, Q. (2000) Phenylpropanoid Glycosides from Smilax glabra. Phytochemistry, 53, 1051-1055.
http://dx.doi.org/10.1016/S0031-9422(99)00522-1
[8] Li, S.Y., Fuchino, H., Kawahara, N., Sekita, S. and Satake, M. (2002) New Phenolic Constituents from Smilax bracteata. Journal of Natural Products, 65, 262-266.
http://dx.doi.org/10.1021/np010338m
[9] Shao, B., Guo, H., Cui, Y., Ye, M., Han, J., et al. (2007) Steroidal Saponins from Smilax china and Their Anti-Inflammatory Activities. Phytochemistry, 68, 623-630.
http://dx.doi.org/10.1016/j.phytochem.2006.10.026
[10] Pérez de Paz, P.L. and Hernández Padrón, C.E. (1999) Plantas medicinales o útiles en la Flora Canaria. Aplicaciones Populares, Francisco Lemus S.L., La Laguna, 161.
[11] Schaefer, H. and Schoenfelder, P. (2009) Smilax canariensis, S. azorica (Smilacaceae) and the Genus Smilax in Europe. In: Beltrán Tejera, E., Afonso-Carrillo, J., García Gallo, A. and Rodríguez Delgado, O., Eds., Homenaje al Profesor Dr. Wolfredo Wildpret de la Torre, Instituto de Estudios Canarios, La Laguna (Tenerife. Islas Canarias), Monografía LXX-VIII, 297-306.
[12] Abdala, S., Martín-Herrera, D., Benjumea, D., et al. (2008) Diuretic Activity of Smilax canariensis, an Endemic Canary Island Species. Journal of Ethnopharmacology, 119, 12-16.
http://dx.doi.org/10.1016/j.jep.2008.05.025
[13] Abdala, S., Martín-Herrera, D., Benjumea, D., et al. (2012) Diuretic Activity of Some Smilax canariensis Fractions. Journal of Ethnopharmacology, 140, 277-281.
http://dx.doi.org/10.1016/j.jep.2012.01.017
[14] Harbone, J.B. and Williams, C.A. (2000) Advances in Flavonoid Research Since 1992. Phytochemistry, 55, 481-504. http://dx.doi.org/10.1016/S0031-9422(00)00235-1
[15] Küpeli, E. and Yesilada, E. (2007) Flavonoids with Anti-Inflammatory and Antinociceptive Activity from Cistus laurifolius L. Leaves through Bioassay-Guided Procedures. Journal of Ethnopharmacology, 112, 524-530. http://dx.doi.org/10.1016/j.jep.2007.04.011
[16] Vidyalakshmi, K., Kamalakannan, P., Viswanathan, S., et al. (2010) Antinociceptive Effect of Certain Dihydroxy Flavones in Mice. Pharmacology Biochemistry and Behavior, 96, 1-6.
http://dx.doi.org/10.1016/j.pbb.2010.03.010
[17] Li, Y.D., Frenz, C.M., Chen, M.H., et al. (2011) Primary Virtual and in Vitro Bioassay Screening of Natural Inhibitors from Flavonoids against COX-2. Chinese Journal of Natural Medicines, 9, 156-160.
[18] Higgs, J., Wasowski, C., Loscalzo, L.M., et al. (2013) In Vitro Binding Affinities of a Series of Flavonoids for μ-Opi-oid Receptors. Antinociceptive Effect of the Synthetic Flavonoid 3, 3-Dibromoflavanone in Mice. Neuropharmacology, 72, 9-19.
http://dx.doi.org/10.1016/j.neuropharm.2013.04.020
[19] Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes.
[20] Siegmund, E., Cadmus, R. and Lu, G. (1957) A Method for Evaluating Both Non-Narcotic and Narcotic Analgesics. Experimental Biology and Medicine, 95, 729-731.
http://dx.doi.org/10.3181/00379727-95-23345
[21] Hunskaar, S. and Hole, K. (1987) The Formalin Test in Mice. Dissociation between Inflammatory Pain. Pain, 30, 103-114.
http://dx.doi.org/10.1016/0304-3959(87)90088-1
[22] Alviano, D.S., Rodrigues, K.F., Leitao, S.G., et al. (2004) Antinociceptive and Free Radical Scavenging Activities of Cocos nucifera L. (Palmae) Husk Fiber Aqueous Extract. Journal of Ethnopharmacology, 92, 269-273. http://dx.doi.org/10.1016/j.jep.2004.03.013
[23] Levy, G., Tuschima, T. and Amsel, L.P. (1972) Limited Capacity for Salicyl Phenolic Glucuronide Formation and Its Effect on the Kinetics of Salicylate Elimination in Man. Clinical Pharmacology & Therapeutics, 13, 258.
[24] Barrot, M. (2012) Tests and Models of Nociception and Pain in Rodents. Neuroscience, 211, 39-50. http://dx.doi.org/10.1016/j.neuroscience.2011.12.041
[25] Le Bars, D., Gozariu, M. and Cadden, S.W. (2001) Animal Models of Antinociception. Pharmacological Reviews, 53, 597-652.
[26] Lucarini, R., Bernardes, W.A., Ferreira, D.S., et al. (2013) In Vivo Analgesic and Anti-Inflammatory Activities of Rosmarinus officinalis Aqueous Extract, Rosmarinic Acid and Its Acetyl Ester Derivative. Pharmaceutical Biology, 51, 1087-1090.
http://dx.doi.org/10.3109/13880209.2013.776613
[27] Kawabata, A. (2011) Prostaglandin E2 and Pain—An Update. Biological and Pharmaceutical Bulletin, 34, 1170-1173. http://dx.doi.org/10.1248/bpb.34.1170
[28] Soldi, C., Pizzolatti, M.G., Luiz, A.P., et al. (2008) Synthetic Derivatives of the α- and β-Amyrin Triterpenes and Their Properties. Bioorganic & Medicinal Chemistry, 16, 3377-3386.
http://dx.doi.org/10.1016/j.bmc.2007.12.008
[29] Udobang, J.A., Nwafor, P.A. and Okokon, J.E. (2010) Analgesic and Antimalarial Activities of Crude Leaf Extract and Fractions of Acalypha wilkensiana. Journal of Ethnopharmacology, 127, 373-378. http://dx.doi.org/10.1016/j.jep.2009.10.028
[30] Pinheiro, M.M.G., Radulovic, N.S., Miltojevic, A.B., et al. (2014) Antinociceptive Esters of N-Methylanthranilic Acid: Mechanism of Action in Heat-Mediated Pain. European Journal of Pharmacology, 727, 106-114. http://dx.doi.org/10.1016/j.ejphar.2013.12.042
[31] Prajapati, V.D., Maheriya, P.M., Jani, G.K., et al. (2014) Carrageenan: A Natural Seaweed Polysaccharide and Its Applications. Carbohydrate Polymers, 105, 97-112.
http://dx.doi.org/10.1016/j.carbpol.2014.01.067
[32] Bhandare, A.M., Kshirsagar, A.D., Vyawahare, N.S., et al. (2010) Potential Analgesic, Anti-Inflammatory and Antioxidant Activities of Hydroalcoholic Extract of Areca catechu L. Nut. Food and Chemical Toxicology, 48, 3412-3417. http://dx.doi.org/10.1016/j.fct.2010.09.013
[33] Rodrigues, I.V., Souza, J.N.P., Silva, A.C.G., et al. (2013) Antiedematogenic and Antinociceptive Effects of Leaves Extracts from Protium spruceanum Benth. (Engler). Pharmacognosy Journal, 5, 6-12. http://dx.doi.org/10.1016/j.phcgj.2012.08.001
[34] Cuzzocrea, S., Sautebin, L., De Sarro, G., et al. (1999) Role of IL-6 in the Pleurisy and Lung Injury Caused by Carrageenan. Journal of Immunology, 163, 5094-5104.
[35] Eddouks, M., Chattopadhyay, D. and Zeggwagh, N.A. (2012) Animal Models as Tools to Investigate Antidiabetic and Anti-Inflammatory Plants. Evidence-Based Complementary and Alternative Medicine, 2012, 1-14.
[36] Posadas, I., Bucci, M., Roviezzo, F., et al. (2004) Carrageenan-Induced Mouse Paw Oedema Is Biphasic, Age-Weight Dependent and Displays Differential Nitric Oxide Cyclooxygenase-2 Expression. British Journal of Pharmacology, 142, 331-338.
http://dx.doi.org/10.1038/sj.bjp.0705650
[37] Toffoli-Kadri, M.C., Carollo, C.A., Dias LourenÇo, L., et al. (2014) In Vivo and in Vitro Anti-Inflammatory Properties of Achyrocline alata (Kunth) DC. Journal of Ethnopharmacology, 153, 461-468. http://dx.doi.org/10.1016/j.jep.2014.03.008
[38] Toker, G., Kupeli, E., Memisoglu, M., et al. (2004) Flavonoids with Antinociceptive and Anti-Inflammatory Activities from the Leaves of Tilia argentea (Silver Linden). Journal of Ethnopharmacology, 95, 393-397.
http://dx.doi.org/10.1016/j.jep.2004.08.008
[39] Fawzy, A.A., Vishwanath, B.S. and Franson, R.C. (1988) Inhibition of Human Non-Pancreatic Phospholipases A2 by Retinoids and Flavonoids. Agents and Actions, 25, 394-400.
http://dx.doi.org/10.1007/BF01965048
[40] Mori, T.A. and Beilin, L.J. (2004) Omega-3 Fatty Acids and Inflammation. Current Atherosclerosis Reports, 6, 461-467.
http://dx.doi.org/10.1007/s11883-004-0087-5

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