Chemical Pharmacognosy in the Era of Integrated Natural-Product Discovery: From Traditional Knowledge to Therapeutic Translation

Abstract

Natural products have played a central role in the development of medicines and continue to provide structurally diverse molecules, pharmacological leads, and molecular frameworks for contemporary drug discovery. Chemical pharmacognosy has traditionally focused on the isolation, characterization, and biological evaluation of constituents obtained from medicinal plants and other natural sources. The discipline has progressively expanded through advances in analytical chemistry, molecular biology, metabolomics, computational science, genomics, and biotechnology. Consequently, modern chemical pharmacognosy is increasingly positioned as an integrated discovery framework rather than a discipline restricted to the isolation of individual compounds. This review examines the transition from traditional knowledge-guided investigation toward a multidisciplinary approach that combines ethnopharmacological information, botanical authentication, chemical profiling, dereplication, metabolomics, molecular networking, bioactivity screening, genome mining, synthetic biology, and translational pharmaceutical development. Particular emphasis is placed on the complementary roles of liquid chromatography–high-resolution tandem mass spectrometry, nuclear magnetic resonance spectroscopy, chemometrics, molecular networking, and biosynthetic gene-cluster analysis in accelerating natural-product discovery. The review also considers the progression from bioactive constituents to validated therapeutic candidates, including mechanism-of-action studies, pharmacokinetics, toxicological assessment, formulation, quality control, and scalable production. Challenges associated with complex mixtures, dereplication, reproducibility, sustainability, authentication, microbial contamination, adulteration, and access and benefit-sharing are discussed. An integrated workflow is proposed in which traditional knowledge and biodiversity provide hypotheses, modern analytical and computational tools prioritize chemical space, biological experiments establish activity and mechanism, and pharmaceutical sciences support translation. Such integration can improve the efficiency, reproducibility, sustainability, and translational potential of natural-product research.