Akademik Veri Yönetim Sistemi
Letters in Drug Design and Discovery, 2026 (SCI-Expanded, Scopus)
Background Phytochemicals, bioactive compounds derived from medicinal plants, have long contributed to drug discovery by providing diverse chemical scaffolds and broad biological activities. Despite strong preclinical evidence across inflammatory, metabolic, infectious, and neoplastic diseases, the clinical translation of many phytochemicals has been inconsistent, largely due to pharmacokinetic limitations, safety concerns, and regulatory challenges. Objective This review critically examines the translational landscape of phytochemicals by adopting a mechanism-centered framework that links molecular actions to quantitative ADMET constraints, formulation strategies, and human clinical outcomes, with the aim of identifying factors that govern successful or failed clinical advancement. Methods A comprehensive literature search was conducted across major scientific databases, including PubMed, Scopus, and Web of Science, covering studies published between 2000 and 2025. Original research articles, clinical trials, and recent reviews were screened using predefined inclusion criteria. Evidence was synthesized by grouping phytochemicals according to shared molecular mechanisms and mapping these to pharmacokinetic profiles, safety data, and stages of clinical development. Results Phytochemicals exert pleiotropic effects through modulation of oxidative stress, inflammatory signaling pathways such as NF-κB and MAPK, and apoptosis-related processes. However, compounds such as curcumin and resveratrol demonstrate limited clinical efficacy despite robust mechanistic activity, primarily due to poor oral bioavailability and rapid metabolism. In contrast, formulation optimization and regulatory alignment have enabled the successful clinical development of select botanical drugs. Conclusion This review highlights that mechanistic potency alone is insufficient for clinical translation. Integrating early ADMET evaluation, rational formulation design, and regulatory planning is essential to advance phytochemicals from experimental promise to clinically viable therapeutics.