Molecular engineering for bitterness masking of natural products: from decoding structure-taste relationships to structure-driven bitterness suppression

Natural products have emerged as a vital source of active ingredients in medicine, food, and cosmetics due to their unique biological activities, safety profiles, and sustainability. However, most bioactive compounds in natural products are intensely bitter, limiting their use in pharmaceuticals and foods. The bitter taste attributes vary markedly among different compound classes, predominantly due to their structural characteristics. By decoding the structure-taste relationships of bitter substances, this paper synthesizes masking strategies tailored to different types of bitter compounds based on prior research findings from our group. Specifically, carrageenan and analogous substances encapsulate bitter alkaloids through electrostatic induction; pectin, gum arabic, and xanthan gum mitigate the bitterness of polyphenols and flavonoids by enhancing water solubility, introducing steric hindrance, and eliciting electrostatic repulsion; stevioside and its counterparts form micelles with bitter saponins, thereby reducing bitterness perception. Compared to conventional multi-flavorant blending, these structure-driven bitterness suppression strategies are simpler, more efficient, and precise, with enhanced specificity and applicability to improve natural products' palatability. Integrated with AI technologies, these strategies can be fully applied, expand the market potential of natural products in pharmaceutical and food applications, and establish a basis for developing versatile bitterness-masking solutions.