Supramolecular interactions: A simple and effective strategy to enhance the stability and skincare benefits of caffeic acid

Caffeic acid (CA) is a sustainable bioactive compound with abundant skincare benefits; however, its poor solubility and stability make its clinical application challenging. In this study, a salt with abundant supramolecular interactions (SupCA) was prepared from CA and matrine to address these issues. The structure-activity relationship of SupCA was systematically studied using density functional theory, molecular docking, and molecular dynamics simulations. The supramolecular interactions in SupCA modified the electronic distribution of CA, leading to enhanced water solubility, stability, antioxidant ability, and affinity for key proteins in inflammatory signaling pathways. The skincare benefits of SupCA were comprehensively tested and compared with those of a mixture of CA and matrine to further investigate the impact of supramolecular interactions on the bioactivity of SupCA. A 28-day treatment with a SupCA emulsion reduced facial redness, a* value, fine lines under the eyes, and crow's feet wrinkles in participants by 65.62 %, 13.27 %, 45.07 %, and 38.09 %, respectively, which were significantly superior to those of the mixture emulsion. This demonstrated the vital role of supramolecular interactions in enhancing bioactivity, consistent with the calculation findings. In addition, SupCA exhibited excellent anti-acne, skin repair, and whitening properties, with no adverse responses and 100 % user satisfaction, making it a safe, versatile, and efficient ingredient in cosmetics.