Tetrandrine exerts anti-inflammatory and HaCaT cell-protective effects in atopic dermatitis by targeting miR-494-3p

Abstract

The active ingredient, Tetrandrine (TET), derived from the Nidus Vespae, exhibits diverse pharmacological activities, including anti—inflammatory, antioxidant, and immunomodulatory effects. To demonstrate the effectiveness of TET in the treatment of atopic dermatitis and its underlying mechanism of action. The atopic dermatitis cell model was established through the induction of HaCaT cells with lipopolysaccharide (LPS) and interferon-gamma (IFN—γ). The DNCB-mouse model was constructed using 2,4-dinitrobenzenesulfonic acid sodium salt (DNCB). By means of network pharmacology, the effective components of the Nidus Vespae and the common genes shared with atopic dermatitis were explored. The expression levels of interleukin-6 (IL-6), tumor necrosis factor (TNF), and immunoglobulin E (IgE) were determined using the enzyme-linked immunosorbent assay (ELISA) method. The cell viability of HaCaT cells was detected using the Cell Counting Kit-8 (CCK-8). The expression level of miR-494-3p was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). TET suppressed the secretion of IL-6 and TNF by HaCaT cells stimulated by LPS + IFN-γ, and decreased the IgE levels in the serum of DNCB-mice, along with the IL-6 and TNF levels in the skin lesions. Simultaneously, TET treatment diminished the scratching frequency in the DNCB-mice. Mechanistically, both in vitro and in vivo experiments collectively indicated that TET modulates miR—494—3p to mitigate the inflammatory response in HaCaT cells induced by LPS + IFN—γ, as well as the scratching behavior and DNCB-like symptoms in DNCB-mice. TET mitigated the inflammatory response in LPS + IFN-γ-induced HaCaT cells, as well as the DNCB-like symptoms and scratching frequency in DNCB-mice via miR-494-3p.