Comparative RNA-seq Analysis of Single Compounds versus Polyherbal Formulations in Cancer Prevention

Abstract

Cancer prevention through dietary and botanical interventions relies increasingly on multicomponent polyherbal formulations rather than individual phytochemicals, yet mechanistic comparisons remain limited. This comprehensive review synthesizes current knowledge on transcriptomic analysis comparing single compounds versus polyherbal formulations in cancer prevention models, emphasizing synergistic versus antagonistic gene regulation at the network level. We examine how RNA-seq reveals coordinated transcriptional changes across broader pathways in polyherbal preparations compared to single compound treatments, identify molecular mechanisms underlying synergy and antagonism, and discuss network pharmacology approaches for rationalizing herb combinations. Particular emphasis is placed on traditional polyherbal formulations including Ayurvedic preparations (Triphala, Kanchnar guggulu), Chinese herbal medicines, and novel phytochemical combinations demonstrating enhanced efficacy. The review discusses Bliss independence and Loewe additivity models for quantifying synergy at the transcriptomic level, cellular and molecular context dependence of synergistic responses, and how single compounds often demonstrate antagonistic interactions with conventional chemotherapy while polyherbal formulations bypass such antagonism through alternative pathway engagement. Critical challenges in standardization, regulatory approval, and post-marketing surveillance of polyherbal formulations are addressed, alongside future perspectives for rational polypharmacy design and personalized combination approaches based on individual transcriptomic profiles.