Unveiling the pharmacological basis of Rhodiola crenulata for atopic dermatitis: A multi-model approach combining zebrafish, mouse studies, and intelligent computational analysis.

BACKGROUND

Atopic dermatitis (AD) is a complex inflammatory skin disorder. Rhodiola crenulata extract (RC) contains bioactive compounds with potential benefits for AD, but its mechanisms are not fully elucidated.

METHODS

A DNCB-induced AD mouse model and zebrafish models were used to evaluate efficacy and multi-dimensional activities. RC was separated into microfractions by preparative liquid chromatography. An OPLS-DA model, based on zebrafish bioactivity and LC-MS profiling, predicted active compounds, which were validated. Mechanisms were investigated via transcriptome sequencing, Western blot, qPCR, network pharmacology, and molecular docking.

RESULTS

RC alleviated AD-like symptoms in mice, reducing epidermal thickening, mast cell infiltration, and splenomegaly. Four active monomers were identified, with kaempferol and naringenin showing the most prominent anti-inflammatory and analgesic effects, while salidroside exhibited strong antioxidant activity. RC and its active components primarily inhibited the NLRP3/Caspase-1/IL-1β axis, while also modulating oxidative stress (e.g., NOX2, PRDX2), cAMP/PKA signaling, and skin barrier-repair pathways. Network pharmacology and molecular docking confirmed efficient binding of four core compounds to NLRP3, CASP1, and IL-1B.

CONCLUSION

This study demonstrates that RC alleviates AD by inhibiting the NLRP3 inflammasome pathway, identifying kaempferol, naringenin, salidroside and rhodiosin as key constituents, providing a foundation for developing RC as a natural AD therapeutic.