Skin photoaging is a common skin problem characterized by degradation of skin structure function and collagen damage. Litchi chinensis seed, a traditional Chinese medicine, contains a variety of bioactive components and shows potential value in the treatment of various diseases. In this study, we investigated the protective mechanism of lychee seed against skin photoaging based on computational biology and network pharmacology approaches. Eight major active constituents of lychee seed, including mannitol, β-sitosterol, ghrelin, stigmasterol, stigmasterol, epicatechin, and quercetin, were obtained through the screening of the Traditional Chinese Medicine (TCM) Systematic Pharmacology Database (TCMSPD). GeneCards and OMIM databases were used to search for targets related to skin photoaging, and 71 common targets were obtained by intersecting with the active ingredients of lychee seed to construct a network of “traditional Chinese medicine-active ingredient-gene target-disease”, and the GO functional enrichment analysis showed that these targets were involved in 101 biological processes, which were mainly related to the activities of transcription factors, nuclear receptors and neurotransmitter receptors, etc. Western Blot experiments confirmed that these targets were involved in the activities of transcription factors, nuclear receptors and neurotransmitters. Western Blot assay confirmed that lychee seed could reduce skin collagen destruction by inhibiting the expression of IκBα, IKKα and NF-κBP65 proteins in the NF-kB pathway. Microarray data analysis showed that GSE181022 and GSE107361 gene chips identified 671 and 3158 differentially expressed genes, respectively, and five core targets were obtained after taking the intersection with drug targets. The results showed that lychee seed could effectively reduce skin tissue aging, mainly through regulating the NF-κB signaling pathway, which provided a scientific basis for lychee seed to combat skin photoaging.
