Complex herbal formulas are often interpreted through the language of synergy, yet the observation that a combination behaves differently from its isolated components does not identify where the interaction occurs or whether the effect satisfies a formal pharmacological definition of synergy. This article develops an original layered interaction model that separates three analytically distinct domains: chemical interactions that alter material state or constituent availability before systemic exposure; exposure-level interactions that modify absorption, distribution, metabolism, elimination, or measured concentration; and pharmacodynamic interactions that alter biological response at matched exposure. The model treats these domains as connected but non-equivalent and proposes that evidence should be assigned to the level directly measured before cross-level inference is attempted. It further distinguishes interaction from synergy by requiring explicit reference models, response endpoints, dose or exposure context, and uncertainty when synergy, additivity, or antagonism is claimed. Chemical self-assembly, transporter- or enzyme-mediated exposure changes, and pathway-level combination effects illustrate why a favorable combined outcome can arise through different mechanisms. The proposed framework therefore emphasizes traceable attribution, competing explanations, and reversible interpretation rather than a compulsory progression toward synergy. Its practical implication is that herbal-formula studies should align analytical chemistry, constituent-resolved pharmacokinetics, and pharmacodynamic comparison designs while using computational predictions as hypothesis-generating evidence. The framework remains conceptual and requires prospective testing across preparations, doses, biological systems, and formal interaction models.
