Anti-Photoaging effects and safety evaluation of chitosan Maillard derivatives: in vitro and in vivo studies

Ultraviolet B (UVB) radiation is a major contributing factor to skin photoaging by accelerating inflammation and collagen degradation. This underscores the critical need to develop natural and safe bioactive compounds to combat UVB-induced skin disease. In this study, different chitosan Maillard reaction products (CMRPs) were prepared and characterized to evaluate their anti-photoaging activities, mechanisms of action and safety. The Maillard reaction altered the morphology of chitosan from a loose powder into a crosslinked structure. The resulting CMRPs exhibited enhanced DPPH and ABTS radical scavenging activities as well as increased elastase inhibitory effects. All six CMRPs were non-toxic to HaCaT cells and improved the viability of UVB-induced photoaged cells, with CG-6 demonstrating the most potent anti-photoaging activity. Mechanistic investigations revealed that CG-6 significantly inhibited the accumulation of reactive oxygen species (ROS) in photoaged HaCaT cells, enhanced the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), suppressed the expression of matrix metalloproteinases (MMPs) and inflammatory factors, and regulated the expression of key genes in the MAPK signaling pathway, thereby exerting protective effects against photoaging. Oral administration of CG-6 for 28 days did not cause any apparent organ damage in mice. There were no significant differences in organ indices, histopathological examination, hematological parameters, liver and kidney function markers, or antioxidant enzyme activity levels between the CG-6-treated and control groups. These findings indicate that CG-6 does not cause negative effect on the health of mice. Overall, this study provides a strong theoretical foundation for the application of Maillard reaction products, particularly CG-6 in the development of anti-photoaging functional foods.