CDK8/19-IN-4

BALB/c (male, 6-8 weeks old, about 20 g)^[1]

5 mg/kg; 10 mg/kg; 20 mg/kg

for 7 days

Markedly alleviated IMQ-induced pathological skin features in a dose-dependent manner.
Significantly reduced erythema, scaling, and thickness scores and substantially decreased cumulative PASI scores; LW-1 exhibited improved efficacy relative to C46 under the tested conditions.
No significant changes in body weight were observed.
Attenuated IMQ-induced splenomegaly, as indicated by a reduced spleen index.
H&E staining showed that LW-1 alleviated epidermal hyperplasia, inflammatory cell infiltration, and skin thickening.
Immunohistochemical analysis of Ki-67 showed a pronounced reduction in keratinocyte proliferation after LW-1 administration.
In flow cytometry analysis, CD4+Foxp3+ Treg cells among CD4+ T cells were: IMQ 7.58%; LW-1 5 mg/kg 9.01%; LW-1 10 mg/kg 10.8%; LW-1 20 mg/kg 12.0%; control 13.1%.
Restored Treg populations in a dose-dependent manner, and at the high dose LW-1 showed superior effects relative to C46.
IMQ stimulation upregulated IL-6, TNF-α, CXCL1, and CXCL2 mRNA expression, while LW-1 markedly suppressed their expression in a dose-dependent manner.
ELISA showed that LW-1 significantly reduced serum protein levels of IL-6, TNF-α, CXCL1, and CXCL2.