Intervention and mechanism of Xiaoyin Anshen Yin (消银安神饮) in treatment of psoriasis combined with sleep disorders

doi:10.19852/j.cnki.jtcm.2025.03.004

Abstract

Abstract:

OBJECTIVE: To explore the therapeutic mechanisms of Xiaoyin Anshen Yin (消银安神饮, 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.

Key words: psoriasis, melatonin, nuclear receptor subfamily 1, group F, member 1, NF-kappa B, sleep disorder

DIAO Ruohan, DUAN Xingwu, LI Lingling, QU Tiange, FENG Huishang, CHEN Guangshan. Intervention and mechanism of Xiaoyin Anshen Yin (消银安神饮) in treatment of psoriasis combined with sleep disorders[J]. Journal of Traditional Chinese Medicine, 2025, 45(3): 552-560.

Figures/Tables 4

Figure 1 Effect of drug-containing serum on oxidative stress indexes A: cells of each group were stained with 2', 7'-dichlorodihydrofluorescein diacetate probe, the average fluorescence intensity was used to represent the level of intracellular ROS for statistical analysis. A1: flow cytometry analysis results; A2: relative levels of ROS. B: cells of each group were stained using JC-1 probe, Q2 is JC-1 multimer and its percentage, Q3 is JC-1 monomer and its percentage, and mitochondrial membrane potential was statistically analyzed by multimer/monomer to represent mitochondrial membrane potential. B1: NC; B2: Model; B3: XYAS; B4: QXAS; B5: LXJD; B6: mitochondrial membrane potential levels. C: The expression levels of SOD2 and Cyt-c in each group was detected via western blot method. C1: immunoblot bands for SOD2 and Cyt-c; C2: relative protein levels of SOD2; C3: relative protein levels of Cyt-c. NC: 10% NC serum; Model: 25 ng/mL TNF-α + 10% NC serum; XYAS: 25 ng/mL TNF-α + 10% XYAS serum; QXAS: 25 ng/mL TNF-α + 10% QXAS serum; LXJD: 25 ng/mL TNF-α + 10% LXJD serum. SOD2: superoxide dismutase 2; Cyt-c: Cytochrome-c; NC: Negative control; XYAS: Xiaoyin Anshen; QXAS: Qinxin Anshen; LXJD: Liangxue Jiedu; TNF-α: tumor necrosis factor‐α. Statistical analyses were measured using one-way analysis of variance for multiple comparisons. Data were presented as mean ± standard deviation (n ≥ 3). Compared with the Model group, aP < 0.001, cP < 0.01, dP < 0.05; compared with the NC group, bP < 0.001, eP < 0.05.

Figure 2 Effect of drug-containing serum on apoptosis A: the cells of each group were stained using AnnexinV-FITC/PI double staining. Q1-Q4 represented cell debris and necrotic cells, late apoptotic cells, early apoptotic cells, non-apoptotic cells and the percentage of apoptotic cells respectively. A1: NC; A2: Model; A3: XYAS; A4: QXAS; A5: LXJD. B: The percentage of Q2 + Q3 (early apoptotic cells + late apoptotic cells) was used for statistical analysis. NC: 10% NC serum; Model: 25 ng/mL TNF-α + 10% NC serum; XYAS: 25 ng/mL TNF-α + 10% XYAS serum; QXAS: 25 ng/mL TNF-α + 10% QXAS serum; LXJD: 25 ng/mL TNF-α + 10% LXJD serum. NC: Negative control; XYAS: Xiaoyin Anshen; QXAS: Qinxin Anshen; LXJD: Liangxue Jiedu; TNF-α: tumor necrosis factor‐α; FITC: fluorescein isothiocyanate; PI: propidium iodide. Statistical analyses were measured using one-way analysis of variance for multiple comparisons. Data were presented as mean ± standard deviation (n = 3). Compared with the Model group, aP < 0.05, cP < 0.001; compared with the NC group, bP < 0.05, dP < 0.001, eP < 0.01.

Figure 3 Effect of drug-containing serum on the activation of NF-κB pathway A: immunoblot bands for p-p65, p65 and IκBα; B: ratios of p-p65 to p65; C: relative protein levels of IκBα. NC: 10% NC serum; Model: 25 ng/mL TNF-α + 10% NC serum; XYAS: 25 ng/mL TNF-α + 10% XYAS serum; QXAS: 25 ng/mL TNF-α + 10% QXAS serum; LXJD: 25 ng/mL TNF-α + 10% LXJD serum. NF-κB: nuclear factor kappa-B; p-p65: phosphorylated p65; IκBα: inhibitor of kappa-B alpha; NC: Negative control; XYAS: Xiaoyin Anshen; QXAS: Qinxin Anshen; LXJD: Liangxue Jiedu; TNF-α: tumor necrosis factor‐α. Statistical analyses were measured using one-way analysis of variance for multiple comparisons. Data were presented as mean ± standard deviation (n ≥ 3). Compared with the Model group, aP < 0.01, cP < 0.001, eP < 0.05; compared with the NC group, bP < 0.01, dP < 0.05.

Figure 4 Effects of drug-containing serum on melatonin and RORα A: The melatonin content in the drug-containing serum of each group tested by ELISA method; B: immunoblot bands for RORα; C: relative protein levels of RORα. NC: 10% NC serum; Model: 25 ng/mL TNF-α + 10% NC serum; XYAS: 25 ng/mL TNF-α + 10% XYAS serum; QXAS: 25 ng/mL TNF-α + 10% QXAS serum; LXJD: 25 ng/mL TNF-α + 10% LXJD serum. MLT: melatonin; RORα: retinoid related orphan receptor alpha; NC: Negative control; XYAS: Xiaoyin Anshen; QXAS: Qinxin Anshen; LXJD: Liangxue Jiedu; TNF-α: tumor necrosis factor‐α; ELISA: enzyme linked immunosorbent assay. Statistical analyses were measured using one-way analysis of variance for multiple comparisons. Data were presented as mean ± standard deviation (n ≥ 3). Compared with the NC serum, aP < 0.001; compared with the Model group, bP < 0.05; compared with the NC group, cP < 0.05.

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