Cimifugin Mechanism of Action from Saposhnikovia divaricata in the Treatment of Atopic Dermatitis

摘要

The present study aimed to explore the mechanism of action of cimifugin, the primary active ingredient in Saposhnikovia divaricata (Turcz.) Schischk., Apiaceae, in treating atopic dermatitis. BALB/c mice were grouped, modeled, and medicated, followed by skin lesion scoring, hematoxylin-eosin, and toluidine blue staining. The levels of thymic stromal lymphopoietin and immunoglobulin E in skin homogenate and serum were measured. An in vitro inflammation model was created based on lipopolysaccharide-stimulated RAW264.7 cells to detect the nitrite concentration in the cell supernatants and the levels of tumor necrosis factor-alpha, interleukin-13, interleukin-31, and interleukin-33. Compared with the model group, mice in the high, medium, and low-dose cimifugin groups showed significantly alleviated atopic dermatitis-like symptoms. The expression levels of inflammatory factors in mouse serum and skin homogenate significantly decreased (p < 0.01, p < 0.001). The cell proliferation rate experiment showed that cimifugin had no toxic effect on cells within 100 mu mol<middle dot>l(-1), indicating a safe therapeutic concentration range. The Griess assay revealed that high-dose cimifugin could significantly inhibit NO release in LPS-stimulated RAW264.7 cells (p < 0.001). Enzyme-linked immunosorbent assay results showed that, compared with the RAW264.7 group, the RAW264.7 + LPS group showed increased levels of TNF-alpha as well as IL-13, IL-31, and IL-33 in the cell culture supernatants (p < 0.001), successfully establishing the inflammation model. Compared with the RAW264.7 + LPS group, the levels of TNF-alpha, IL-13, IL-31, and IL-33 in the cell culture supernatants of the RAW264.7 + LPS + Cim-H, M, and L dose groups decreased (p < 0.05). The results of comparison among various groups showed that cimifugin in S. divaricata can intervene in the onset and development of atopic dermatitis by inhibiting keratinocyte hypertrophy, mast cell infiltration, as well as the secretion of related inflammatory factors by T helper cells 2 and macrophages.

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