Polypharmacology by Design: Prioritizing Plant-Derived Compounds Across Inflammation, Oxidative Stress, Metabolic Dysfunction, and Immune Modulation

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Plant-derived compounds are frequently described as multi-target agents, yet broad claims of activity across many pathways do not by themselves establish therapeutically meaningful polypharmacology. This Original Conceptual Model Article develops a mechanism-centered framework for prioritizing plant-derived compounds across inflammation, oxidative stress, metabolic dysfunction, and immune modulation. The article positions polypharmacology as a design logic in which candidate compounds are prioritized when reported target or pathway activities converge across biologically connected mechanisms, rather than when they simply accumulate predicted targets or unspecific bioactivity claims. The proposed approach integrates compound identity, phytochemical class, source context, evidence type, target and pathway convergence, mechanistic coherence, exposure plausibility, safety considerations, disease-context relevance, translational readiness, and validation needs. Inflammation and oxidative stress are treated as interdependent regulatory domains involving inflammatory signaling, cytokine networks, redox balance, and antioxidant-response pathways, while metabolic dysfunction and immune modulation are framed through immunometabolic crosstalk, gut–metabolic interactions, and context-dependent immune regulation. The main contribution is a structured prioritization logic that distinguishes confirmed mechanisms, pathway associations, predicted targets, phenotypic observations, and conceptual hypotheses. Practically, the model is intended to support more disciplined phytochemical screening, systems pharmacology interpretation, and translational candidate selection without implying that multi-target activity, antioxidant capacity, or natural origin is sufficient evidence of efficacy or safety.