RESUMO
Psoriasis is a chronic inflammatory disease characterized by immunological imbalance and vasodilation. Many triggering factors for psoriasis initiate inflammation via the activation of NF-κB. Narrow-band ultraviolet B (NB-UVB) irradiation can be used as a general treatment for psoriasis, although the molecular mechanism has not yet been determined. The aim of this study was to elucidate the potential molecular mechanism of NB-UVB irradiation therapy on psoriasis. We collected serum samples from patients with psoriasis and healthy control, and detected the expression of inflammatory factors by ELISA. In addition, we established mouse model of psoriasis. After different doses of NB-UVB irradiation, the proportion of CD4+ , CD8+ , and CD11c+ cells in mouse spleen was detected by flow cytometry. Meanwhile, the expression of inflammatory factors in the damaged skin of mice was detected by RT-PCR and Western blot analysis, and mouse serum levels of inflammatory factors were detected by ELISA. Our results showed that NB-UVB irradiation regulated the expression of inflammatory factors in psoriasis patients. In mice, high-dose NB-UVB irradiation effectively eliminated IMQ-induced psoriasis-like dermatitis and inhibited the expression of pro-inflammatory factors. In conclusion, our results indicate that NB-UVB irradiation could regulate the expression of inflammatory factors and attenuate psoriasis plaques.
Assuntos
Psoríase , Terapia Ultravioleta , Animais , Humanos , CamundongosRESUMO
Background: Jianpi Yangxue Qufeng Compound (JPYXQFC) is a Chinese medicine widely used in the clinical treatment of atopic dermatitis (AD) and has a significantly therapeutic effect. However, the mechanism of JPYXQFC in AD has been not understood clearly. Objective: This study aimed to explore the effect of JPYXQFC on AD model cells and rats by regulating TLR4/MyD88/NF-κB signaling pathway. Methods: The rats (n > 5) were given JPYXQFC decoction orally twice a day for three days, and their abdominal aortic blood was collected. HaCaT cell proliferation rate was tested by cell counting kit-8 (CCK-8) assays. We induced AD rat model through 2, 4-dinitrofluorobenzene (DNFB). AD rats were given oral JPYXQFC decoction and cetirizine (positive control). HaCaT cells were pretreated with JPYXQFC drug serum or cetirizine for 0.5 h and then stimulated with TNF-α/IFN-γ for 1 h. The mRNA levels of TLR4, MyD88, NF-κB, IL-4, IL-13, MCP1, TNF-α and TSLP were detected by quantitative real-time PCR (Q-RT-PCR), and TLR4/MyD88/NF-κB pathway protein expression was tested by Western blot. The total serum levels of immunoglobulin E (IgE), thymus and activation regulated chemokine/chemokine (C-C motif) ligand 17 (TARC/CCL17) were detected by enzyme-linked immunosorbent assay (ELISA). The epidermal thickness was detected by hematoxylin and eosin (HE) staining. The dermatitis area and score were measured by a ruler and a four-point scoring method, respectively. Results: JPYXQFC significantly inhibited mRNA and protein expression of the TLR4/MyD88/NF-κB pathway and Histone H3 in TNF-α/IFN-γ-induced HaCaT cells and DNFB-induced rats, decreased the mRNA of IL-4, IL-13, MCP1, CCL22, TSLP and the level of AD-related genes IgE and TAEC/CCL17 of TNF-α/IFN-γ-induced HaCaT cells. Meanwhile, JPYXQFC significantly reduced the dermatitis area and dermatitis score in DNFB-induced rats, inhibited the levels of pro-inflammatory cytokines IL-6 and TNF-α, and upregulated FLG, as well as inhibited the levels of IgE and TARC/CCL17 in the serum of AD rats. Conclusion: JPYXQFC alleviates AD by inhibiting the activation of TLR4/MyD88/NF-κB pathway.
RESUMO
Dieting is a basic treatment for lowering hyperuricemia. Here, we aimed to determine the optimal amount of dietary food that lowers serum uric acid (SUA) without modifying the dietary ingredients in rats. Increased SUA was found in food-deprived 45-day-old uricase-deficient rats (Kunming-DY rats), and the optimal amount of dietary food (75% dietary intake) to lower SUA was established by controlling the amount of food given daily from 25% to 100% for 2 weeks. In addition to lowering SUA by approximately 22.5 ± 20.5%, the optimal amount of dietary food given for 2 weeks inhibited urine uric acid excretion, lowered the uric acid content in multiple organs, improved renal function, lowered serum triglyceride, alleviated organ injuries (e.g., liver, kidney and intestinal tract) at the histological level, and down-regulated the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway of the cell cycle (ko04110). Taken together, these results demonstrate that 75% dietary food effectively lowers the SUA level without modifying dietary ingredients and alleviates the injuries resulting from uricase deficiency or hyperuricemia, the mechanism of which is associated with the down-regulation of the cell cycle pathway.
Assuntos
Hiperuricemia , Animais , Ratos , Urato Oxidase , Ácido Úrico , Ciclo Celular , Divisão Celular , Veículos FarmacêuticosRESUMO
Background: Psoriasis is a common chronic inflammatory skin disease with multifactor etiology, characterized by abnormal proliferation and differentiation of keratinocytes. Huang-Lian Jie-Du decoction (HLJDD) is a traditional Chinese medicine prescription with good clinical curative effect on psoriasis. However, its therapeutic mechanisms are still unclear. Methods: The psoriasis model of SKH-1 nude mice was established by imiquimod-induced and HLJDD gavage was given. Hematoxylin and eosin staining were used to evaluate pathological morphologies, and immunohistochemistry was used to detect the expressions of Wnt1, ß-catenin, and c-Myc in psoriasis mice. Western blot was used to examine the expressions of Frizzled-2, LRP5/6, GSK-3ß, APC, Axin2, TCF4, LEF1, cyclin D1, TBX3, EPHB2, and NOTUM enzyme. Results: In this study, HLJDD reduced skin erythema and lesions, decreased the thickness of epidermal and downregulated the expressions of Wnt1, ß-catenin, and c-Myc. Western blot results showed that HLJDD reduced the expressions of Wnt receptors Frizzled-2 and LRP5/6, and Wnt downstream target genes TCF4, LEF1, cyclin D1, TBX3, and EPHB2, while upregulated destruction complex proteins GSK-3ß, APC, and Axin2. Conclusions: HLJDD can effectively treat psoriasis and inhibit the Wnt/ß-catenin signaling pathway at multiple stages.