Supramolecular Tetrahydrocurcumin–Cyclodextrin for Enhanced Antioxidant, Anti-inflammatory, and Whitening Effects

Tetrahydrocurcumin (THC) is an active metabolite of curcumin with similar pharmacological activities, such as anti-inflammatory and antioxidant effects. However, the poor water solubility of THC results in low bioavailability and thus limits its application. We have developed a supramolecular encapsulation delivery system. Firstly, THC and citric acid (CA) were prepared into supramolecular THC-CA, and then hydroxypropyl-β-cyclodextrin (HP-β-CD) was added to prepare supramolecular THC-CA-CD. The supramolecular THC-CA-CD can self-assemble into spherical particles with a diameter of 156 nm in solution, achieving an encapsulation efficiency of 92.43%, aiming to improve its stability and bioavailability. Compared to free THC, the supramolecular THC-CA-CD exhibits stronger antioxidant capacity, anti-inflammatory effects (inhibiting IL-6, TNF-α, and IL-1α), and the ability to inhibit tyrosinase activity. Additionally, the supramolecular THC-CA-CD was used as an active ingredient in a cosmetic cream for efficacy evaluation. The results showed that a 0.5% supramolecular THC-CA-CD skin cream increased the individual type angle (ITA°) value by 46.15%, decreased the melanin index (MI) value by 32.84%, and significantly increased the skin lightness (L) value by 44.06% within 4 weeks. In summary, the supramolecular THC-CA-CD exhibits whitening, antioxidant, and anti-inflammatory effects.