Screening of active constituents in camellia oil against atopic dermatitis via molecular docking and experimental validation: elucidation of the underlying molecular mechanism.

Abstract

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease. The JAK/STAT and PDE4/cAMP pathways are pivotal in driving its inflammation. This study aimed to discover natural JAK1 and PDE4 inhibitors from camellia oil to alleviate AD. METHODS: Utilizing the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we employed a target-based molecular docking approach against key inflammatory targets (JAK1, PDE4B, PDE4D) of AD to screen the compounds in camellia oil. This virtual screening was followed by in vitro enzymatic assays to validate their inhibitory effects. Based on these findings, we employed a DNCB-induced AD mouse model to compare the therapeutic efficacy of (1% and 4%) ( +)-catechin hydrate and (4% and 6%) epicatechin against 1.5% ruxolitinib cream. RESULTS: Although molecular docking screening predicted seven compounds with potential high binding affinity for PDE4B and PDE4D, respectively, subsequent in vitro enzymatic inhibition assays demonstrated that all of these compounds exhibited low inhibitory rates against the enzymes. In comparison, (+)-catechin hydrate and epicatechin not only exhibited excellent binding affinity with JAK1 but also achieved high inhibition rates. Their ICvalues for JAK1 inhibition were 1125.65 ± 0.56 nM and 3531.24 ± 0.17 nM, respectively. Animal studies have demonstrated that both (+)-catechin hydrate and epicatechin can significantly ameliorate symptoms of AD, including reducing the severity of skin lesions and itching behavior, while also suppressing the expression of inflammatory mediators such as TSLP, IL-4, and IL-13. CONCLUSION: In camellia oil, (+)-catechin hydrate and epicatechin are the primary active constituents for the treatment of AD, suggesting that their anti-AD effects were possibly mediated through the suppression of the JAK1-driven inflammatory signaling pathway. This study not only provides a novel utilization strategy for camellia oil, but also offers new insights for the treatment of AD.