To investigate the biological effects of 25-hydroxycholesterol (25-HC) on psoriasis-like mice.

Male BALB/c mice (6-8 weeks old) were randomly divided into four groups (n=6): blank control, model, experimental, and control groups. After dorsal hair removal, all mice were topically treated with 62.5 mg/day of 5% imiquimod cream for 7 consecutive days. The experimental group received 25-HC via gavage, while the control group was administered compound indirubin capsules. The blank and model groups were given an equal volume of saline. On day 8, the Psoriasis Area and Severity Index (PASI) was evaluated, and skin tissue and blood samples were collected.Skin histopathology was evaluated using the Baker scoring system. Oxidative stress markers in blood samples, including SOD, MDA, and GSH, were measured with commercial assay kits. Serum IL-1β levels were detected by ELISA, and mitochondrial damage in epidermal cells was observed via transmission electron microscopy (TEM).

The model group exhibited significantly higher PASI and Baker scores compared to the blank and control groups (P < 0.01 or P < 0.05). Relative to the model group, the experimental group showed further elevated scores (P < 0.05). Oxidative stress markers were significantly altered: MDA levels increased while SOD and GSH activities decreased in both model and experimental groups versus controls (all P < 0.05 or lower). IL-1β levels were highest in the experimental group and lowest in the control group (P < 0.01). TEM observation confirmed that 25-HC aggravated mitochondrial damage, showing swollen morphology, disorganized cristae, and reduced matrix electron density.

25-HC exacerbates the pathological progression of psoriasis by inducing severe oxidative stress and mitochondrial damage, suggesting that targeting 25-HC may represent a novel therapeutic strategy.