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Facilitating Drug Discovery: An Automated High-content Inflammation Assay in Zebrafish
Published on: July 16, 2012
Unveiling the pharmacological basis of Rhodiola crenulata for atopic dermatitis: A multi-model approach combining
Xiongyi Zhang1, Yanfu Wang1, Dongyang Zhao1
1Institute of Traditional Chinese Medicine and Natural Products, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
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.
