Abstract
OBJECTIVE: To explore the therapeutic mechanisms of Xiaoyin Anshen Yin (, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B (NF-κB) pathway. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups, and administered distilled water, XYAS and its two different disassembly prescriptions by gavage respectively. Four types of drug-containing serums corresponding to the four groups were then prepared. Tumor necrosis factor (TNF)-α stimulated HaCaT was used to establish a psoriasis cell model, and the serums and the retinoid related orphan receptor alpha (RORα) inverse agonist were used respectively to intervene in the model. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-6 and melatonin in each group; flow cytometry was used to detect the levels of reactive oxygen species (ROS), mitochondrial membrane potential, and apoptosis; Western blot was used to evaluate the levels of superoxide dismutase 2 (SOD2), cytochrome-c (Cyt-c), inhibitor of kappa-B alpha (IκBα), p65 and phosphorylated p65. RESULTS: XYAS and its disassembly prescriptions inhibited the secretion of inflammatory factors such as IL-6, reduced the ROS content and Cyt-c expression, increased the mitochondrial membrane potential and SOD2 content, promoted the apoptosis in HaCaT cells and inhibited the activation of the NF-κB pathway. XYAS was also found increase the melatonin content. The above effects are beneficial in the treatment of psoriasis combined with sleep disorders. Meanwhile, XYAS no longer had a significant ameliorative effect after applying the RORα inverse agonist, suggesting that the therapeutic effect of XYAS is related to RORα. CONCLUSIONS: The results of this study confirm that XYAS can be utilized for the treatment of psoriasis combined with sleep disorders via inhibiting the NF-κB pathway, anti-inflammatory, antioxidant and pro-apoptotic, which is in part related to the regulatory role of melatonin and its receptor RORα.