Abstract
Most of the currently available drugs are derived from natural sources, but they are used only after extensive chemical modifications to improve their safety and efficacy. Natural products are used in health supplements and cosmetic preparations and have been used as auxiliary drugs or alternative medicines. When used in combination with conventional drugs, these herbal products are known to alter their pharmacokinetics and pharmacodynamics, reducing their therapeutic effects. Moreover, herb-drug interactions (HDIs) may have serious side effects, which is one of the major concerns in health practice. It is postulated that HDIs affect the pathways regulating cytochrome P450 enzymes (CYPs). Betanin, the chief pigment of red beetroot (Beta vulgaris L.), has various types of pharmacological activity, such as anti-inflammatory, antioxidant, and anticancer effects. However, the potential risk of HDIs for betanin has not yet been studied. Thus, we aimed to predict more specific HDIs by evaluating the effects of betanin on CYPs (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), the major phase I metabolic enzymes, using fluorescence-/luminescence-based assays. Our results showed that betanin inhibited CYP3A4 activity in a dose-dependent manner (IC(50) = 20.97 µΜ). Moreover, betanin acted as a competitive inhibitor of CYP3A4, as confirmed by evaluating Lineweaver-Burk plots (Ki value = 19.48 µΜ). However, no significant inhibitory effects were observed on other CYPs. Furthermore, betanin had no significant effect on CYP1A2, CYP2B6, or CYP2C9 induction in HepG2 cells. In conclusion, betanin acted as a competitive inhibitor of CYP3A4, and thus it should be used cautiously with other drugs that require metabolic enzymes as substrates. Additional in vivo studies and clinical trials are needed to further elucidate the HDIs of betanin.