Lim Sung Ho, Bae Seoungpyo, Lee Ho Seon, Han Hyo-Kyung, Choi Chang-Ik
Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea.
BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea.
Pharmaceuticals (Basel). 2023 Aug 30;16(9):1224. doi: 10.3390/ph16091224.
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 ( 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 = 20.97 µΜ). Moreover, betanin acted as a competitive inhibitor of CYP3A4, as confirmed by evaluating Lineweaver-Burk plots ( 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.
目前大多数可用药物都源自天然来源，但只有在经过广泛的化学修饰以提高其安全性和有效性后才会使用。天然产物用于健康补充剂和化妆品制剂，并已用作辅助药物或替代药物。当与传统药物联合使用时，已知这些草药产品会改变其药代动力学和药效学，降低其治疗效果。此外，草药-药物相互作用（HDI）可能会产生严重的副作用，这是健康实践中的主要关注点之一。据推测，HDI会影响调节细胞色素P450酶（CYPs）的途径。甜菜红素是红甜菜（L.）的主要色素，具有多种药理活性，如抗炎、抗氧化和抗癌作用。然而，甜菜红素的HDI潜在风险尚未得到研究。因此，我们旨在通过使用基于荧光/发光的测定法评估甜菜红素对主要的I相代谢酶CYPs（CYP1A2、CYP2B6、CYP2C9、CYP2C19、CYP2D6和CYP3A4）的影响，来预测更具体的HDI。我们的结果表明，甜菜红素以剂量依赖性方式抑制CYP3A4活性（IC = 20.97 μΜ）。此外，通过评估Lineweaver-Burk图（值 = 19.48 μΜ）证实，甜菜红素是CYP3A4的竞争性抑制剂。然而，未观察到对其他CYPs有显著抑制作用。此外，甜菜红素对HepG2细胞中的CYP1A2、CYP2B6或CYP2C9诱导没有显著影响。总之，甜菜红素是CYP3A4的竞争性抑制剂，因此与其他需要代谢酶作为底物的药物合用时应谨慎使用。需要进一步的体内研究和临床试验来阐明甜菜红素的HDI。
