Psoriasis is a recurrent inflammatory skin disease characterized by redness and scaly skin lesions with itchy or painful sensations. Forsythoside A, one of the main active compounds isolated from the fruit of Forsythia suspensa, has been widely applied to treat inflammatory diseases in the clinical use of traditional oriental medicine. However, the effect of forsythoside A on psoriasis remains unclear. This study aimed to explore the therapeutic effects and immune regulation of forsythoside A on psoriasis. C57BL/6 mice were divided into six groups and treated with imiquimod cream on their shaved back skin to induce psoriasis-like dermatitis. Different doses of forsythoside A (5 mg/kg, 10 mg/kg, or 20 mg/kg) were administered to the respective treatment groups. Skin redness, scaling, and ear thickness were measured; keratinocyte proliferation and inflammatory cytokine expression were detected by hematoxylin–eosin and immunohistochemical staining. Th17 cells in the inguinal lymph nodes were detected by flow cytometric analysis. IL-17A levels were measured using ELISA. The results showed that forsythoside A relieved psoriatic skin symptoms such as skin redness, thickness, scaling, and reduced epidermal thickening. The expression of IL-6, IL-17, and Ki-67 was downregulated in the forsythoside-A-treated groups. Th17 cell expression in inguinal lymph nodes and IL-17A secretion was suppressed by forsythoside A. In conclusion, forsythoside A was found to alleviate imiquimod-induced psoriasis-like dermatitis in mice by suppressing Th17 development and IL-17A secretion. These findings demonstrate the feasibility of forsythoside A in treating human psoriasis.

Psoriasis is a chronic autoimmune skin disease with a significant impact on quality of life and potential for severe comorbidities. Inflammation in the skin is induced by immune cells that overexpress pro-inflammatory cytokines, with the Th17 cell playing a crucial role. NLRP3 inflammasome activation is associated with inflammatory diseases and abnormal T cell differentiation. 3H-1,2-dithiole-3-thione (D3T), isolated from cruciferous vegetables, has anti-inflammatory effects and inhibits Th17 differentiation. This study aimed to investigate how D3T reduces skin inflammation and modulates Th17 cell differentiation by inhibiting NLRP3 inflammasome activation. In an imiquimod-induced psoriasis mouse model, D3T treatment demonstrated significant reductions in ear thickness, skin redness, and scaling compared to a control group. Our study also observed decreased expression of ki-67, NLRP3 inflammasome, and cleaved caspase-1 in skin samples, reduced levels of IL-6 and IL-17A in serum samples, and inhibition of Th17 differentiation after D3T application. D3T could also inhibit the expression of NLRP3, caspase-1, and IL-1β in TNF-α stimulated HaCaT cells. The mechanical study also revealed that D3T could inhibit NLRP3 inflammasome activation by inhibiting the JNK pathway in HaCaT cells. These results indicate that targeting NLRP3 inflammasome activation is a promising strategy in the treatment of psoriasis.

Psoriasis is a predominantly Th17 cell-driven chronic autoinflammatory skin disorder. Brevilin A, a natural sesquiterpene lactone extracted from Centipeda minima, has been used as a traditional oriental medicine for allergic diseases for centuries. However, the effects of brevilin A on psoriasis have yet to be established. In this study, we investigated brevilin A to elucidate its potential effects on T cell activities in psoriasis, in animal models and patients. An imiquimod (IMQ)-induced psoriasis-like dermatitis murine model was utilized. Experimental mice were administered different doses of brevilin A (5, 10, 20 mg/kg respectively) for a duration of 5 days. Cutaneous manifestations were measured daily. Under hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC), acanthosis and proinflammatory cytokine expression in the dorsal skin of mice were detected. Enzyme-linked immunosorbent assay (ELISA) was used for the measurement of IL-17A levels in serum samples. Naïve CD4+ T cells, isolated from mice spleen and lymph nodes and from peripheral blood mononuclear cells (PBMCs) of psoriatic patients, were used to evaluate the effects of brevilin A on Th17 differentiation. In brevilin A-treated mice, brevilin A significantly reduced skin redness and scaling; acanthosis as well as IL-6, IL-17A, and ki-67 expressions were downregulated in the dorsal skin, and serum levels of IL-17A were lowered. Brevilin A also inhibited Th17 differentiation. In conclusion, brevilin A demonstrated significant capability in ameliorating skin inflammation in IMQ-induced psoriasis-like dermatitis and could modulate Th17 differentiation. Therefore, brevilin A is potentially pharmacologically effective in the treatment of psoriasis.

The journal retracts the article “Brevilin A Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis and Reduces Th17 Differentiation in Psoriasis Patients”

ObjectivesEvidence guiding treatment sequencing following Janus kinase inhibitor (JAKi) treatment failure in rheumatoid arthritis (RA) remains limited. This study aimed to compare treatment persistence and clinical effectiveness between JAKi cycling and biologic switching after discontinuation of an initial JAKi due to inadequate response.MethodsIn this multicenter retrospective cohort study, only patients who discontinued their first JAKi due to inadequate response were included. The primary outcome was 12-month drug retention. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. The secondary outcomes included reasons for discontinuation within 12 months and clinical effectiveness at 6 months, assessed using the European Alliance of Associations for Rheumatology (EULAR) response criteria.ResultsAmong the 186 patients, 44 (23.7%) cycled to another JAKi and 142 (76.3%) switched to biologic therapy. Cycling was associated with significantly higher 12-month drug retention than switching (IPTW-adjusted hazard ratio, 0.21; 95% CI, 0.08–0.59; P = 0.003). This difference was mainly driven by fewer discontinuations owing to insufficient efficacy. Concomitant glucocorticoid use independently predicted improved retention (adjusted hazard ratio, 0.44; 95% CI, 0.25–0.80; P = 0.007). At 6 months, EULAR good/moderate response rates were not significantly different between groups (78.6% vs. 62.0%), although adjusted analyses suggested a trend favoring cycling (odds ratio, 3.38; 95% CI, 1.02–11.24; P = 0.047).ConclusionsAmong patients with RA who had an inadequate response to their first JAKi, cycling to another JAKi was associated with superior 12-month drug retention with comparable short-term clinical effectiveness.