Unraveling the Curcumin's Molecular Targets and Its Potential in Suppressing Skin Inflammation Using Network Pharmacology and In Vitro Studies

ABSTRACT Curcumin, a polyphenol compound derived from turmeric, has garnered attention for its anti‐inflammatory and antioxidant properties, making it a promising candidate for treating skin inflammation. Despite its potential, the underlying pharmacological effects to skin inflammation remain unclear. Therefore, this study aimed to reveal the curcumin's molecular targets and its potential in suppressing skin inflammation using network pharmacology and in vitro experiments. A total of 7,393 and 239 targets related to curcumin and skin inflammation, respectively, were obtained from public databases. By drawing a Venn diagram, 216 common targets were identified as candidate targets. These targets were subjected to gene function and pathway enrichment analyses, and a protein‐protein interaction network was established to investigate curcumin's impact on inflammation. The gene functions were mainly associated with inflammatory response, membrane raft, and serine‐type endopeptidase activity. The NF‐κB and MAPK pathways could be the major pathways through which curcumin acts on skin inflammation. Ten major targets of curcumin in the treatment of skin inflammation were identified: AKT1, TNF, EGFR, APP, MMP9, STAT3, HIF1A, PTGS2, EP300, and GSK3B. Molecular docking analysis results showed high binding affinity of curcumin to PTGS2, GSK3B, HIF1A, and STAT3, which may contribute to its inhibitory effect on skin inflammation. In vitro experiments confirmed curcumin's anti‐inflammatory effect on inflammation by reducing the expression levels of NO, IL‐1β, and IL‐6 in LPS‐induced HaCaT cells. Taken together, this study reveals major targets and pathways of curcumin in the treatment of skin inflammation, paving the way for invivo and clinical investigations.