Pharmacodynamic evaluation of phenanthridine derivatives in c57bl/6 mice
According to the aforementioned in vitro assays, HCJA121 and HCJA404 effectively stimulated melanin production through a new mode of action that involved targeting of the axin protein. Subsequently, in vivo pharmacodynamic assays were conducted to evaluate the therapeutic effects of HCJA121 and HCJA404 on vitiligo. We used a total of 108 C57BL/6 mice (half male and half female), weighing between 18 and 22 g. We coated 99 mice with 5% HQ for 50 consecutive days to establish a mouse model of vitiligo. The mice were randomly divided into 8 groups: a negative control group, a positive control group (8-MOP), and six groups that were treated with low (0.0425 mg/kg), medium (0.425 mg/kg), or high (4. 25 mg/kg) doses of the compounds. The remaining eight mice were not treated with 5% HQ, and they served as a blank control group. Phenanthridine was administered once daily for 30 days. During the modelling process, the skin of each group of mice was pale, and hair growth was slow. With prolonged modelling, white spots appeared, and the new hair turned white. As shown in Fig. 4a and Table S1, the skin and colour of the newly generated hair in the test area of the vitiligo mice exhibited varying degrees of restoration to black in the groups treated with 8-MOP and the phenanthridine derivatives. Particularly, the skin and hair of vitiligo mice recovered very well after the administration of HCJA121 and HCJA404, even at a low dose, indicating that the clinical symptoms of vitiligo mice were significantly improved, implying that 1 and 2 produce strong curative effects for vitiligo.