Polyphenols as Therapeutic Candidates in the 21 st Century: From Chemical Discovery to Clinical Translation

Polyphenols represent a distinct class of secondary metabolites, whose exploration commenced in the late 18th century, with the isolation of gallic acid from oak galls. Chemically, polyphenols are further categorized into flavonoids and non-flavonoids. While preliminary investigations were constrained by conventional extraction techniques and poor pharmacokinetics, advanced analytical techniques and drug-delivery approaches enable exhaustive characterization, standardization, and enhanced bioavailability of these bioactives. A thorough literature search was conducted using keywords related to polyphenols, to ensure comprehensive data coverage, utilizing scientific databases including PubMed, Scopus, and Web of Science from 2020 to 2026. The present review distinguishes itself from the existing literature by compiling the most recent isolation of polyphenols from natural sources, along with the quantitative assessment of their therapeutic potency, in terms of IC50 values, concentrations, and MICs, extracted from various preclinical, and clinical investigations. The review traces the evolutionary trajectory of the chemical discovery of polyphenols and their translational applications as adjuncts against various disorders, alongside critically examining major challenges in their utilization as evidence-based phytomedicine.