New Potential of Roxatidine Acetate Hydrochloride on Atopic Dermatitis Mouse Model, Human Keratinocytes, and Human Skin Equivalent Model

Atopic dermatitis (AD) is a complex inflammatory skin disorder, characterized by a complicated pathophysiology and a wide range of clinical phenotypes. Roxatidine acetate chloride (RXA) is a precursor of Roxatidine and a histamine H2 receptor antagonist, used for the treatment of gastric ulcers. In this study, we aimed to examine whether RXA had anti-AD effects and determine the underlying molecular mechanism of RXA. The anti-AD effects were examined in Dermatophagoides farinae body (Dfb)-induced AD mouse model, tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes, and human skin equivalent model using ELISA, histological analysis, immunohistochemistry, Western blot, and immunofluorescence. Results showed that RXA treatment significantly alleviated Dfb-induced AD skin symptoms and clinical severity in mice by decreasing the levels of immunoglobulin E, histamine, and inflammatory cytokines. RXA effectively inhibited the expression of adhesive molecules and recovered the filaggrin expression in Dfb-induced AD skin lesions and TNF-α/IFN-γ-stimulated HaCaT keratinocytes. Additionally, RXA significantly upregulated the expression of aryl hydrocarbon receptor and sirtuin1. The anti-AD effects of RXA were associated with suppressed nuclear factor kappa cascade. Overall, our results suggest that RXA may be a potential anti-AD candidate owing to its inhibitory effect against skin inflammation and protection of the skin barrier function in AD.

Influence of Tween 80 Surfactant on the Binding of Roxatidine Acetate and Roxatidine Acetate–loaded Chitosan Nanoparticles to Lysozyme

The drug binding to protein is an attractive research topic. In order to assess the release of RxAc-CsNPs and their binding with lysozyme under physiological conditions, nanocomposite materials based on chitosan (Cs) and Roxatidine acetate (RxAc) in the presence Tween 80 (Tw80) surfactant were developed. The addition of Tw80 to CsNPs increased RxAc release in vitro. In this work, Stern–Volmer plot and thermodynamic results indicated that the mechanism of Lyz with RxAc and Lyz with RxAc-CsNPs was static mechanism and the main forces in both systems were hydrogen bonding and Van der Waals forces, which indicated that the binding reaction in both systems is spontaneous, exothermic and enthalpically driven. Synchronous fluorescence and CD results indicated that the RxAc and RxAc-CsNPs cause change in the secondary construction of Lyz. It was also found that the addition of Tw80 affects the binding constant of drug with protein. Finally, the molecular docking results have also been in accordance with the results of other techniques. Hence, the developed RxAc loaded Chitosan nanoparticles could be used as an effective strategy for designing and application of the antiulcer drugs. Altogether, the present study can provide an important insight for the future designing of antiulcer drugs.