Pharmacological Characterization Of Solanum Cernuum Vell.: 31-norcycloartanones With Analgesic And Anti-inflammatory Properties

Cycloeucalenone (1) and 24-oxo-31-norcycloartanone (2) obtained from Solanum cernuum Vell. were assayed to explore their pharmacologic roles. Previous studies showed that (2) has selective activity against lung tumor cell line (NCIH460) which expresses high levels of COX-2, suggesting its role in inflammatory process, and also a link between chronic inflammation and cancer-associated process. Dichloromethane crude extract (DCE) significantly reduced writhing and stretching induced by 0.8 % acetic acid at a dose of 100, 300, and 600 mg/kg, po; oral administration of different doses of (1) and (2) also displayed significant analgesic and anti-inflammatory effects in the writhing acetic acid test (p < 0.0001). Selected oral doses of both compounds (100 and 50 mg/kg) were assayed in the carrageenan-induced paw edema model. Compound (2) showed significant activity during the early phase (1.5-6 h) and also in the late phase (48 h) (p < 0.01). The anti-nociceptive activity observed for the compounds (1) and (2) and DCE was found to be related to the inhibition of different mediators involved in inflammation and nociceptive process. Both compounds decrease COX-2 protein expression, although only compound (2) reached a significant response (p < 0.05 vs control). However, in vitro Sirtuin 1 activity and TNF-α production in THP-1 macrophages were not affected. © 2013 Springer.223179185Bjorkman, S., Akeson, J., Helfer, M., Fyge, A., Gustafsson, L.L., Cerebral uptake of morphine in the Pig calculated from arteriovenous plasma-concentration gradients - an alternative to tissue microdialysis (1995) Life Sci, 57, pp. 2335-2345Corrêa, M.P., (1984) Dicionário de Plantas Úteis Do Brasil e Das Exóticas Cultivadas, , Imprensa Nacional, Rio de JaneiroCragg, G., Grothaus, P., Newman, D., Impact of natural products on developing new anti-cancer agents (2009) Chem Rev, 109, pp. 3012-3043Dao, T., Le, T., Nguyen, P., Thuong, P., Pham, T., Woo, E., Lee, K., Oh, W., SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis (2010) Panta Medica, 76, pp. 1011-1074Ghosh, S., Hayden, M.S., New regulators of NF-kappa B in inflammation (2008) Nat Rev Immunol, 8, pp. 837-848Grando, R., Antonio, M., Araujo, C., Soares, C., Medeiros, M., De Carvalho, J., Lourenco, A., Lopes, L., Antineoplastic 31-norcycloartanones from Solanum cernuum Vell (2008) Zeitschrif fur Naturforschung Sect C-A J Biosci, 63, pp. 507-514Jain, R., Sharma, A., Gupta, S., Sarethy, I.P., Gabrani, R., Solanum nigrum: Current perspectives on therapeutic properties (2011) Altern Med Rev, 16, pp. 78-85Kang, N., Zhang, J., Qiu, F., Tashiro, S., Onodera, S., Ikejima, T., Inhibition of EGFR signaling augments oridonin-induced apoptosis in human laryngeal cancer cells via enhancing oxidative stress coincident with activation of both the intrinsic and extrinsic apoptotic pathways (2010) Cancer Lett, 294, pp. 147-158Kongkathip, N., Dhumma-upakorn, P., Kongkathip, B., Chawananoraset, K., Sangchomkaeo, P., Hatthakitpanichakul, S., Study on cardiac contractility of cycloeucalenol and cycloeucalenone isolated from Tinospora crispa (2002) Journal of Ethnopharmacology, 83 (1-2), pp. 95-99. , DOI 10.1016/S0378-8741(02)00210-6, PII S0378874102002106Lorenzi, H., Matos, F.J.A., (2000) Plantas Medicinais No Brasil, Nativas e Exóticas, , Instituto Plantarum de Estudos da flora Ltda, São PauloNunes, F.P.B., Sampaio, S.C., Santoro, M.L., Sousa-e-Silva, M.C.C., Long-lasting anti-inflammatory properties of Crotalus durissus terrificus snake venom in mice (2007) Toxicon, 49 (8), pp. 1090-1098. , DOI 10.1016/j.toxicon.2007.01.017, PII S0041010107000475Pedernera, M.A., Guardia, T., Calderón, C., Rotelli, A.E., De La Rocha, N.E., Saad, J.R., Verrilli, M.A.L., Pelzer, L.E., Anti-inflammatory effect of Acacia visco extracts in animal models (2010) Inflammopharmacology, 18, pp. 253-260Penissi, A., Vera, M., Mariani, M., Rudolph, M., Cenal, J., De Rosas, J., Fogal, T., Piezzi, R., Novel antiulcer alpha, beta-unsaturated lactones inhibit compound 48/80-induced mast cell degranulation (2009) Eur J Pharmacol, 612, pp. 122-130Posadas, 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 (2004) British Journal of Pharmacology, 142 (2), pp. 331-338. , DOI 10.1038/sj.bjp.0705650Praman, S., Mulvany, M.J., Allenbach, Y., Marston, A., Hostettmann, K., Sirirugsa, P., Jansakul, C., Effects of an n-butanol extract from the stem of Tinospora crispa on blood pressure and heart rate in anesthetized rats (2011) J Ethnopharmacol, 133, pp. 675-686Rajic, A., Akihisa, T., Ukiya, M., Yasukawa, K., Sandeman, R.M., Chandler, D.S., Polya, G.M., Inhibition of trypsin and chymotrypsin by anti-inflammatory triterpenoids from Compositae flowers (2001) Planta Medica, 67 (7), pp. 599-604. , DOI 10.1055/s-2001-17350Ramírez-Cisneros, M., Rios, M., Déciga-Campos, M., Aguilar-Guadarrama, A., Phytochemical study and anti-inflammatory, antidiabetic and free radical scavenger evaluations of Krameria pauciflora methanol extract (2012) Molecules, 17, pp. 861-872Rodrigues, V.E.G., Carvalho, D.A., Etnobotanical survey of medicinal plants in the dominion of meadows in the region of the Alto Rio Grande, Minas Gerais (2001) Revista Ciência e Agrotecnologia, 25, pp. 102-123Shafiee, A., Bagheri, M., Shekarchi, M., Abdollahi, M., The antinociceptive activities of 1-(4-aryl-2-thiazolyl)-3,5- disubstituted-2 pyrazolines in mouse writhing test (2003) Journal of Pharmacy and Pharmaceutical Sciences, 6 (3), pp. 359-361. , http://www.ualberta.ca/~csps/JPPS6(3)/M.Abdollahi/pyrazoline.htmSouza-Brito, A., (1994) Manual de Ensaios Toxicológicos in Vivo, , Editora UNICAMP, CampinasSpindola, H.M., Servat, L., Denny, C., Rodrigues, R.A.F., Eberlin, M.N., Cabral, E., Sousa, I.M.O., Foglio, M.A., Antinociceptive effect of geranylgeraniol and 6a,7b-dihydroxyvouacapan- 17b-oate methyl ester isolated from Pterodon pubescens Benth (2010) BMC Pharmacol, 10, pp. 1-10Takahashi, T., Kozaki, K.-I., Yatabe, Y., Achiwa, H., Hida, T., Increased expression of COX-2 in the development of human lung cancers (2002) Journal of Environmental Pathology, Toxicology and Oncology, 21 (2), pp. 177-181Vendramini-Costa, D., De Castro, I., Ruiz, A., Marquissolo, C., Pilli, R., De Carvalho, J., Effect of goniothalamin on the development of Ehrlich solid tumor in mice (2010) Bioorg Med Chem, 18, pp. 6742-6747Vlachojannis, J.E., Cameron, M., Chrubasik, S., Medicinal use of potato-Derived products: A systematic review (2010) Phytother Res, 24, pp. 159-162Yang, X.W., Li, S.M., Wu, L., Li, Y.L., Feng, L., Shen, Y.H., Tian, J.M., Zhang, W.D., Abiesatrines A-J: Anti-inflammatory and antitumor triterpenoids from Abies georgei Orr (2010) Org Biomol Chem, 8, pp. 2609-2616Yeung, F., Hoberg, J.E., Ramsey, C.S., Keller, M.D., Jones, D.R., Frye, R.A., Mayo, M.W., Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase (2004) EMBO Journal, 23 (12), pp. 2369-2380. , DOI 10.1038/sj.emboj.7600244Yoshizaki, T., Milne, J., Imamura, T., Schenk, S., Sonoda, N., Babendure, J., Lu, J., Olefsky, J., SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes (2009) Mol Cell Biol, 29, pp. 1363-1374Yoshizaki, T., Schenk, S., Imamura, T., Babendure, J., Sonoda, N., Bae, E., Oh, D., Olefsky, J., SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity (2010) Am J Physiol Endocrinol Metab, 298, pp. E419-E42