Safranal, a plant secondary metabolite isolated from saffron, has been reported for several promising pharmacological properties toward the management of Alzheimer's disease. In the present study, we observe and report for the first time about several druglike attributes of safranal, such as adherence to Lipinski's rule of five; optimum lipophilicity; high permeability; low blood-to-plasma ratio; less to moderate propensity to interact with P-glycoprotein (P-gp) or breast cancer-resistant protein (BCRP) transporters; and high plasma protein binding as common to most of the marketed drugs using in vitro and ex vivo models. In spite of the above attributes, in vivo oral absorption was found to be very poor, which is linked to the structural integrity of safranal in simulated gastric fluid, simulated intestinal fluid, plasma, and liver microsomes. Moreover, the presence of unsaturated aldehyde moiety in safranal remains in equilibrium with its hydroxylated acetal form. Further research work is required to find out the stable oral absorbable form of safranal by derivatization of its aldehyde group without losing its potency.

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Bedaquiline (TMC-207) is a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB). Moreover, there is a present and growing concern for natural-product-mediated drug interaction, as these are inadvertently taken by patients as a dietary supplement, food additive, and medicine. In the present study, we investigated the impact of 20 plant-based natural products, typically phenolics, on in vivo oral bedaquiline pharmacokinetics, as previous studies are lacking. Three natural phenolics were identified that can significantly enhance the oral exposure of bedaquiline upon coadministration. We further investigated the possible role of all of the phytochemicals on in vitro P-glycoprotein (P-gp) induction and inhibition and CYP3A4 inhibition in a single platform as bedaquiline is the substrate for both P-gp and CYP3A4. In conclusion, curcumin, CC-I (3′,5–dihydroxyflavone-7-O-β-d-galacturonide-4′-O-β-d-glucopyranoside), and 6-gingerol should not be coadministered with bedaquiline to avoid untoward drug interactions and, subsequently, its dose-dependent adverse effects.