Flavonoids, Alkaloids, and Polyphenols in Experimental Therapeutics

Flavonoids, alkaloids, and polyphenols represent some of the most pharmacologically rich classes of plant-derived compounds. Molecules such as quercetin, berberine, colchicine, resveratrol, and curcumin have demonstrated broad biological activity — including anti-inflammatory, anticancer, neuroprotective, and cardiometabolic effects — across extensive preclinical literature. Yet despite this promise, the vast majority of these compounds have failed to advance beyond early-stage investigation. Poor bioavailability, metabolic instability, limited target selectivity, and inadequate pharmacokinetic profiles remain persistent bottlenecks that continue to prevent clinical translation.Closing this gap requires a systematic, pipeline-oriented approach: one that begins with rigorous chemical characterization and mechanistic understanding, advances through structure-activity relationship (SAR) analysis and structural optimization, and culminates in pharmacokinetic refinement, innovative delivery strategies, and robust preclinical validation. This Research Topic brings that pipeline into focus — using flavonoids, alkaloids, and polyphenols as a shared scaffold to explore the experimental pharmacology tools and strategies that can move natural compounds from biological curiosity to credible therapeutic candidate.The scope is intentionally translational. Rather than organizing by disease area, this collection centers on the research stages and methodological approaches that are critical to drug discovery success — applied across disease contexts including cancer, metabolic syndrome, inflammation, neurodegeneration, and cardiovascular disease.This Research Topic welcomes original research, reviews, and perspectives addressing, but not limited to, the following themes:Chemical characterization and bioactivity profiling: metabolomic and phytochemical analysis of natural extracts correlated with pharmacological activity, including high-throughput and computational screening approachesMechanistic studies: molecular, cellular, and epigenetic mechanisms underlying the bioactivity of flavonoids, alkaloids, and polyphenols, including intracellular signaling pathways and multi-target engagementStructure-activity relationships (SAR) and lead optimization: systematic evaluation of structural features governing potency, selectivity, and stability; rational design of semi-synthetic analogs and derivatives with improved drug-like propertiesPharmacokinetics, bioavailability, and metabolic stability: ADME profiling, gut microbiota interactions, and strategies to overcome the pharmacokinetic limitations of natural compound scaffoldsNovel delivery systems: nanoparticle-based, lipid-based, and other advanced formulation approaches to enhance bioavailability, targeted delivery, and therapeutic efficacyNetwork pharmacology and polypharmacology: multi-target and systems-level approaches to characterizing the complex pharmacological profiles of these compounds and identifying therapeutically relevant targetsCombination strategies and synergy: interaction studies with conventional therapeutics, including mechanistic rationale and preclinical evidence for synergistic or additive effectsHerb-drug interactions and preclinical safety: effects on drug-metabolizing enzymes and transporters, organ-specific toxicity, and therapeutic window assessment in experimental modelsWe particularly encourage studies that integrate pharmacology, analytical chemistry, computational modeling, and formulation science to address the translational challenges that remain central to the development of flavonoids, alkaloids, and polyphenols as drug candidates. Topic editors: Jesus-Alfredo Araujo-Leon, Rolffy Rubén Ortiz-Andrade, Pankul Kotwal Source: https://www.frontiersin.org/research-topics/82011/flavonoids-alkaloids-and-polyphenols-in-experimental-therapeutics