To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Objective::To detect the expression levels of peripheral blood Treg/Th17 cells and related cytokines in patients with Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) with different traditional Chinese medicine (TCM) syndrome " Yanghuang-Yinyanghuang-Yinhuang" , in order to explore the cellular immunological characteristics of different TCM syndromes of liver failure. Method::The 32 cases of patients with HBV-ACLF in early, middle and late stages in line with the " Yanghuang-Yinyanghuang-Yinhuang" TCM syndrome grouping were selected. Flow cytometry was used to detect the frequency expression of Treg/Th17 cells in peripheral blood. The expression levels of interleukin-10(IL-10), transforming growth factor-β(TGF-β), interleukin-17A(IL-17A), tumor necrosis factor-α(TNF-α) and interleukin-23(IL-23) were detected by cytometric bead array (CBA). The expressions of transcription factor forkhead box P3(FoxP3) and retinoid-related orphan nuclear receptor-γt(ROR-γt) mRNA were detected by Real-time PCR. The SPSS 20.0 software was applied in data statistics and processing to analyze the expression characteristics of Treg/Th17 cells and related cytokines in patients with different TCM syndrome types of HBV-ACLF. Result::The patients with HBV-ACLF Yanghuang syndrome were mainly distributed in the early stage of liver failure, those with Yinyanghuang syndrome were mainly distributed in the middle stage, and those with Yinhuang syndrome were distributed in the late stage. From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, the frequency of Treg and Th17 cells gradually increased, and the differences among the groups were statistically significant (P<0.05). From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, Treg cytokines IL-10, TGF-β gradually increased, and the differences among the groups were statistically significant (P<0.05). Th17 cytokines IL-17A, TNF-α, IL-23 gradually increased, of which IL-17A were differences between Yanghuang syndrome and the Yinyanghuang syndrome, as well as Yanghuang syndrome and Yinhuang syndrome (P<0.05). From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, the expression of FoxP3 was gradually decreased, while that of ROR-γt was gradually increased, and the differences among the groups were statistically significant (P<0.01). Conclusion::There is a certain correlation between the different course of early, middle and late stages of HBV-ACLF and the distribution of TCM syndromes. The frequency of Treg and Th17 cells and the correlation of IL-17A, TGF-β and IL-10 with TCM syndrome differentiation are related, suggesting that Treg and Th17 cells have a certain reference value for the diagnosis of patients with HBV-ACLF and the syndrome differentiation of TCM syndromes.