Modulation of cytochrome P450 3A4 mediated quinine metabolism in healthy volunteers by two honey samples from different floral and geographical sources

Background: Honey is widely used both for its nutritional and medicinal benefits and reports exist to suggest it may alter the disposition of conventional drugs whose metabolism is mediated by CYP3A4. The study aimed at investigating the effect of multiple dose administration of honey sourced from two different geographical zones in Nigeria, on an antimalarial, quinine and its CYP3A4 mediated metabolism.Methods: In a randomized cross-over study, twenty healthy volunteers divided into two groups A and B [A used honey (HA) from Northern and B used honey (HB) from Eastern Nigeria; n=10 respectively] received single oral doses of 600 mg quinine sulphate tablet alone  and after 7 days administration of 10 ml of honey (HA or HB)  twice daily. Blood samples collected at the 16th hour following quinine administration were subjected to HPLC analysis.Results: Compared to baseline, 10 ml of honey HA significantly increased (0.86±0.22 versus 1.36±0.43) (p<0.05; Wilcoxon test); mean metabolic ratio of quinine (3-hydroxyquinine/quinine) in group A subjects. On the other hand, administration of honey HB resulted in a non-significant reduction (p>0.05) (0.84±0.19 versus. 0.69±0.34) of the metabolic ratio of quinine in group B volunteers. Also, the geometric mean [95% CI: 0.63(0.45, 0.91)] of quinine metabolic ratio in the presence of honey HA alone was significantly increased (p=0.02, t-test).Conclusions: Honey sample from Northern Nigeria significantly stimulated CYP3A4-mediated quinine metabolism as reflected by an increased metabolic ratio of quinine. In conclusion some honey samples may have the potential to significantly modulate CYP3A4 activity, thus honey effects cannot be generalized

Elucidation of chemical profiles and molecular targets of Mondia whitei leave fractions bioactive as novel therapeutics: an in vitro and in silico assay

Abstract Background Mondia whitei root is often used in Africa as a local therapeutic agent for libido enhancement. The fractions of the M. whitei leaves (MWL) lack chemical characterization of their bioactive components and possible molecular targets. We characterized and investigated its molecular target as therapeutic agents in an in vitro and in silico assay. Mineral compositions, antioxidant, and GC-MS characterization were studied. The cytotoxicity effect was measured on HeLa and HT-29 cells by MTT assay. In silico potential inhibitors of Cathepsin B (CathB) as a cancer biomarker were determined. Results The flame photometry produced marked Na+ and K+. GC-MS revealed eighteen bioactive components. The fractions (chloroformic 47.00, ethanolic 45.52, and aqueous 40.13) of MWL caused a higher inhibition ratio compared to standards. The MWL showed a significant cytotoxic effect on the treated cell lines at concentrations of 150 and 200 μg/ml and 100, 150, and 200 μg/ml for HT-29 and HeLa cells, respectively. Ten bioactives (MWL 4, 5, 6, 8, 9, 10, 14, 15, 17, and 18) showed potential inhibition of CathB with binding affinities of −4.40 to −8.3 Kcal/Mol. However, MWL 4, 9, 14, and 17 which have higher binding affinities (−6.7, −7.1, −8.2, and −8.3, respectively) than the standard inhibitor (−6.5) were the lead molecules. Conclusion These chemical profiles and potential molecular targets unraveled in this study propose that MWL has a promising anticancer activity. Graphical Abstrac