To enhance the anti-aging and anti-inflammatory effect of bakuchiol and retinol by combining a tripeptide via the PPAR-γ signaling pathway

Objectives To prevent skin aging that induced by chronic inflammation and collagen depletion, along with the consequent decline in elasticity and wrinkles formation. Methods A novel formulation was developed to counter inflammatory and prevent collagen losing with low cytotoxicity to human foreskin fibroblast (HFF) cells, comprising bakuchiol and retinol at a 9:1 ratio (each at 10 uM) and combined with 50 ppm Trifluoroacetyl Tripeptide-2 (Anti-Pr 100, a PPAR-γ inhibitor). Results Colift-A enhanced the transcription levels of COL1A 1 to 338.01%, COL3A 1 to 150.61% and ELN to 248.28% of control levels. Concurrently, it effectively downregulated the transcription levels of pro-inflammation genes, particularly MIP-1α and IL -8, to 44.96% and 47.37% compared to controls, respectively. Clinically, Colift-A significantly improved skin aging indicators in participants, the undereye wrinkles reduced by 15.43% at 28 d and 15.87% at 56 days, crow’s feet decreased by 13.23% at 28 days and 13.74% at 56 days, and nasolabial folds were reduced by 20.20% at 28 days and 20.71% at 56 days. Additionally, skin elasticity, as measured by R2 values, improved by 20.79% at 28 days and 6.02% at 56 days. Conclusions A potential anti-aging and anti-inflammation formula is suggested, which effectively mitigates the appearance of skin wrinkles and laxity while maintaining skin elasticity, by inhibiting the PPAR-γ signaling pathway. The research Registration Number is: 11915, and the preclinical study has received approval from the Shanghai Ethics Committee and complied with the ethical standards outlined in the Declaration of Helsinki with (No. SECCR2024-184-01).