Abstract
The genus Erythrina, Fabaceae, is widely distributed in tropical and subtropical regions. Their flowers, fruits, seeds and bark are frequently used in folk medicine for its effects on the central nervous system such as anticonvulsant, antidepressant, analgesic, sedative, and hypnotic effects. Erythraline has been reported as one of the active compounds from Erythrina, but until now there are no pharmacokinetics data about this compound and only few results showing a putative metabolism were reported. To improve the information about erythraline metabolism, this article reports and discusses, for the first time, the in vitro metabolism biotransformation of erythraline by cytochrome P450 enzymes.
Article PDF
Avoid common mistakes on your manuscript.
References
Arita, T., Miyazaki, S., Teramoto, S., Yoshitama, K., 2014. Major anthocyanin biosynthesis in the brilliant crimson petals from Erythrina crista-galli L. Sci. Hortic. 168, 272–280.
Callejon, D.R., Riul, T.B., Feitosa, L.G.P., Guaratini, T., Silva, D.B., Adhikari, A., Shrestha, R.L.S., Marques, L.M.M., Baruffi, M.D., Lopes, J.L.C, Lopes, N.P., 2014. Leishmanicidal evaluation of tetrahydroprotoberberine and spirocyclic erythrina-alkaloids. Molecules 19, 5692–5703.
Chen, T.L., Zhang, Y.B., Xu, W., Kang, T.G., Yang, X.W., 2014. Biotransformation of isoimperatorin by rat liver microsomes and its quantification by LC-MS/MS method. Fitoterapia 93, 88–97.
Clements, M., Li, L., 2011. Strategy of using microsome-based metabolite production to facilitate the identification of endogenous metabolites by liquid chromatography mass spectrometry. Anal. Chim. Acta 685, 36–44.
Cusack, K.P., Koolman, H.F., Lange, U.E.W., Peltier, H.M., Piel, L., Vasudevan, A., 2013. Emerging technologies for metabolite generation and structural diversification. Bioorg. Med. Chem. Lett. 23, 5471–5483.
Faggion, S.A., Cunha, A.O.S., Fachim, H.A., Gavin, A.S., Santos, W.F., Pereira, A.M.S., Beleboni, R.O., 2011. Anticonvulsant profile of the alkaloids (+)-erythravine and (+)-11-α-hydroxy-erythravine isolated from the flowers of Erythrina mulungu Mart ex Benth (Leguminosae-Papilionaceae). Epilepsy Behav. 20, 441–446.
Flausino Jr., O., Pereira, A.M., Bolzani, V.S., de Souza, R.L.N., 2007a. Effects of ery-thrinian alkaloids isolated from Erythrina mulungu (Papilionaceae) in mice submitted to animal models of anxiety. Biol. Pharm. Bull. 30, 375–378.
Flausino Jr., O., Santos, L.A., Verli, H., Pereira, A.M., Bolzani, V.S., de Souza, R.L.N., 2007b. Anxiolytic effects of erythrinian alkaloids from Erythrina mulungu.]. Nat. Prod. 70, 48–53.
Fraga, A.G.M., Silva, L.L., Fraga, C.A.M., Barreiro, E.J., 2011. CYPlA2-mediated biotransformation of cardioactive 2-thienylidene-3, 4-methylenedioxybenzoylhydrazine (LASSBio-294) by rat liver microsomes and human recombinant CYP enzymes. Eur. J. Med. Chem. 46, 349–355.
Guaratini, T., Silva, D.B., Bizaro, A.C., Sartori, L.R., Humpf, H.U., Lopes, N.P., Lotufo, L.V.C., Lopes, J.L.C., 2014. In vitro metabolism studies of erythraline, the major spiroalkaloid from Erythrina verna. BMC Complement. Altern. Med. 14 (61), 2–5.
Juma, B.F., Majinda, R.R.T., 2004. Erythrinaline alkaloids from the flowers and pods of Erythrina lysistemon and their DPPH radical scavenging properties. Phytochem-istry 65, 1397–1404.
Kurita, K.L., Linington, R.G., 2015. Connecting phenotype and chemotype: high-content discovery strategies for natural products research. J. Nat. Prod. 78, 587–596.
Mantle, P.G., Laws, I., Widdowson, D.A., 1984. 8-Oxo-erythraline, a naturally-occurring principal alkaloid from Erythrina crista-galli. Phytochemistry 23, 1336–1338.
Marques, L.M.M., Silva Jr., E.A., Gouvea, D.R., Vessecchi, R., Pupo, M.T., Lopes, N.P., Kato, M.J., De Oliveira, A.R.M., 2014. In vitro metabolism of the alkaloid piplartine by rat liver microsomes. J. Pharm. Biomed. 95, 113–120.
Messiano, G.B., Santos, R.A.S., Ferreira, L.S., Simoes, R.A., Jabor, V.A.P., Kato, M.J., Lopes, N.P., Pupo, M.T., de Oliveira, A.R.M., 2013. In vitro metabolism study of the promising anticancer agent the lignan (-)-grandisin. J. Pharm. Biomed. 72, 240–244.
Moreira, F.L., Souza, G.H.B., Rodrigues, I.V., Lopes, N.P., De Oliveira, A.R.M., 2013. A non-michaelian behavior of the in vitro metabolism of the pentacyclic triterpene alfa and beta amyrins by employing rat liver microsomes. J. Pharm. Biomed. 84, 14–19.
Niehues, M., Barros, V.P.M., Emery, F.S., Dias-Baruffi, M., Assis, M.D., Lopes, N.P., 2012. Biomimetic in vitro oxidation of lapachol: a model to predict and analyse the in vivo phase I metabolism of bioactive compounds. Eur. J. Med. Chem. 54, 804–812.
Nowak, P., Wozniakiewicz, M., Koscielniak, P., 2014. Simulation of drug metabolism. Trends Anal. Chem. 59, 42–49.
Ogbourne, S.M., Parsons, P.G., 2014. The value of nature’s natural product library for the discovery of new chemical entities: the discovery of ingenolmebutate. Fitoterapia 98, 36–44.
Perdigao, P.S., Serrano, M.A.R., Flausino Jr., O., Bolzani, V.S., Guimaraes, M.Z.P., Castro, N.G., 2013. Erythrina mulungu alkaloids are potent inhibitors of neuronal nicotinic receptor currents in mammalian. PLoS ONE 8, e82726.
Santos, M.D., Martins, P.R., Santos, P.A., Bortocan, R., Iamamoto, Y., Lopes, N.P., 2005. Oxidative metabolism of 5-O-caffeoylquinic acid (chlorogenic acid), a bioactive natural product, by metalloporphyrin and rat liver mitochondria. Eur. J. Pharm. Sci. 26, 62–70.
Santos, M.D., Iamamoto, Y., Lopes, N.P., 2008. HPLC-ESI-MS/MS analysis of oxidizes di-caffeoylquinic acids generated by metalloporphyrin-catalydes reactions. Quim. Nova 31, 767–770.
Spaggiari, D., Geiser, L., Serge, R., 2014. Coupling ultra-high-pressure liquid chromatography with mass spectrometry for in-vitro drug-metabolism studies. Trends Anal. Chem. 63, 129–139.
Wanjala, C.C.W., Juma, B.F., Bojase, G., Cache, B.A., Majinda, R.R.T., 2002. Erythrinaline alkaloids and antimicrobial flavonoids from Erythrina latissima. Planta Med. 68, 640–642.
Yuan, L., Jia, P., Sun, Y., Zhao, C., Zhi, X., Sheng, N., Zhang, L., 2014. Study of in vitro metabolism of m-nisoldipine in human liver microsomes and recombinant cytochrome P450 enzymes by liquid chromatography-mass spectrometry. J. Pharm. Biomed. 97, 65–71.
Acknowledgements
The authors would like to thank FAPESP (Process: 2009/51812-0, 2011/13281-2, 2012/18031-7, 2014/20302-4 and 2014/50265-3), CNPq (168114/2014-3), INCT if and RHAE for fellowships and financial support.
Author information
Authors and Affiliations
Contributions
LMMM, FAA, TG, DBS, DRC conducted extraction and isolation of the eritralin and metabolites from plant and in microsomal bio-transformation, respectively and the interpretation of all these data. LMMM, ARMO, NPL, JLCL and TG wrote and revised the manuscript. All authors read and approved the final manuscript.
Corresponding authors
Ethics declarations
The authors declare no conflicts of interest.
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Marques, L.M.M., Aguiar, F.A., da Silva, D.B. et al. Microsomal metabolism of erythraline: an anxiolitic spiroalkaloid. Rev. Bras. Farmacogn. 25, 529–532 (2015). https://doi.org/10.1016/j.bjp.2015.05.011
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1016/j.bjp.2015.05.011