Background : Specioside (SP – Fig 1 ) is a glycosylated iridoid esterified with a phenylpropanoid moiety present in Tabebuia genus (Bignoniaceae). The hydroethanolic extract of Tabebuia aurea inhibit leukocyte infiltration and paw edema, reduce hemorrhage, myotoxicity and hydrogen peroxide production induced by Bothrops neuwiedi venom [1]. Besides, the outstanding pharmacological potential of SP is due its modulation on the Hsp90 protein activity, associated with the development of almost all the types of cancer [2]. Therefore, since SP is a drug candidate, it is important to evaluate its potential to interact with the metabolism of other drugs. In this context, the present work aimed to evaluate the in vitro inhibitory effect of SP on human CYP450 major isoforms to assess SP-drug interactions. Methods : Specifics reactions catalyzed by CYP450 isoforms were monitored in the presence and absence of SP (100 µM) employing human liver microsomes. The inhibition of each probe substrate metabolism was determined and IC50 values were obtained for the CYP450 isoforms significantly inhibited. Results : SP at SP at 100 µM presents weak inhibitory potential for CYP1A2 (50% of inhibition). No significative inhibition by SP at 100 µM was observed for CYP2C9 (25%), as well as for CYP2C19 (6%), CYP2D6 (5%), CYP2E1 (3%), and CYP3A4/5 (20% for midazolam 1’-hydroxylation and no inhibition for nifedipine oxidation). Conclusion : These results present important information about SP-drug interactions. The very low inhibitory potential of SP against the major CYP450 isoforms indicates that its concomitant intake with other drugs metabolized by these isoforms may not be a problem due to the low SP-drug interactions. Acknowledgments : We are grateful to FAPESP, CNPq and CAPES for financial support.
Fig 1. Chemical structure of specioside (SP)
References: [1] Reis FP, Bonfa IMS, Cavalcante RB et al. J Ethnopharmacol 2014; 158: 352-357. [2] Dal Piaz L, Vassalo A, Chini MG et al. Plos One 2012; 7: e43316.