Shannar Ahmad, Chou Pochung Jordan, Peter Rebecca, Dave Parv Dushyant, Patel Komal, Pan Yuxin, Xu Jiawei, Sarwar Md Shahid, Kong Ah-Ng
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854 USA.
Graduate Program in Pharmaceutical Sciences, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854 USA.
Curr Pharmacol Rep. 2025;11(1):6. doi: 10.1007/s40495-024-00388-6. Epub 2024 Dec 5.
Dietary phytochemicals, bioactive compounds derived from plants, have gained increasing attention for their potential role in cancer prevention. Among these, NRF2 (nuclear factor erythroid 2-related factor 2) activating dietary phytochemicals such as curcumin, sulforaphane, ursolic acid, and cyanidin have demonstrated significant antioxidant and anti-inflammatory properties, making them promising agents in chemoprevention. This review examines the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of these dietary phytochemicals, with a focus on their NRF2-mediated effects in cancer prevention.
Preclinical studies have highlighted the potential of these dietary phytochemicals to modulate oxidative stress and inflammation, key drivers of carcinogenesis. We explore the complexity of their PK/PD properties, influenced by factors such as bioavailability, metabolism, and drug interactions. While most of these phytochemicals follow two compartmental PK, their anti-oxidant and anti-inflammatory effects follow the indirect response (IDR) model. Furthermore, we discuss the application of physiologically based pharmacokinetic (PBPK) modeling to simulate the behavior of these compounds in humans, providing insights for clinical translation.
The integration of PK-PD analysis into the development of dietary phytochemical-based therapies offers a pathway to optimize dosing strategies, enhance therapeutic efficacy, and improve safety. This review underscores the importance of these compounds as part of cancer interception strategies, particularly in the early stages of cancer development, where they may offer a natural, less toxic alternative to conventional therapies.
膳食植物化学物质，即源自植物的生物活性化合物，因其在癌症预防中的潜在作用而受到越来越多的关注。其中，激活NRF2（核因子红细胞2相关因子2）的膳食植物化学物质，如姜黄素、萝卜硫素、熊果酸和花青素，已显示出显著的抗氧化和抗炎特性，使其成为化学预防中有前景的药物。本综述研究了这些膳食植物化学物质的药代动力学（PK）和药效动力学（PD）特征，重点关注它们在癌症预防中由NRF2介导的作用。
临床前研究突出了这些膳食植物化学物质调节氧化应激和炎症的潜力，而氧化应激和炎症是致癌作用的关键驱动因素。我们探讨了其PK/PD特性的复杂性，这些特性受生物利用度、代谢和药物相互作用等因素影响。虽然这些植物化学物质大多遵循二室PK模型，但其抗氧化和抗炎作用遵循间接反应（IDR）模型。此外，我们讨论了基于生理的药代动力学（PBPK）模型在模拟这些化合物在人体中的行为方面的应用，为临床转化提供见解。
将PK-PD分析整合到基于膳食植物化学物质的疗法开发中，为优化给药策略、提高治疗效果和改善安全性提供了一条途径。本综述强调了这些化合物作为癌症拦截策略一部分的重要性，特别是在癌症发展的早期阶段，它们可能为传统疗法提供一种天然、毒性较小的替代方案。
