Abstract:

Zeng Yi *, Shi Mengqi, Yang Huan, He Ping, Wang Youwei, Du Junrong. *Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China Corresponding authors: Wang Youwei, Email: wangyouwei2000@163.com; Du Junrong, Email: dujr_1@163.com 【Abstract】 Objective To explore the anti-inflammatory and antipruritic effects of Chushizhiyang ointment in a mouse model. Methods A total of 40 male 8-week-old BALB/c mice were included in this study, and randomly and equally divided into 4 groups. A mouse model of atopic dermatitis （AD） was established in three groups of mice by repeated application of 2,4-dinitroflurobenzene （DNFB） to shaved abdominal skin for sensitization and to shaved dorsal skin for stimulation. After establishment of the AD model, the three groups were topically treated with sodium chloride physiological solution （model group）, hydrocortisone cream （hydrocortisone group） and Chushizhiyang ointment （Chushizhiyang group） respectively for 14 consecutive days. The remaining group receiving no sensitization or treatment served as the normal control group. All the mice were sacrificed 12 hours after the final treatment, and the dorsal skin of mice was resected followed by the determination of skin thickness and weight as well as hematoxylin-eosin （HE） staining and toluidine blue staining for the counting of leukocytes and mast cells respectively. Moreover, enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of interferon-gamma （IFN-γ）, tumor necrosis factor alpha （TNF-α）, interleukin 4 （IL-4） and IL-5 in dorsal skin lesions. In addition, a local skin itching model was induced by histamine phosphate in Hartley guinea pigs, which was used to explore the effect of Chushizhiyang ointment on itch thresholds. Results Compared with the model group, both the Chushizhiyang group and hydrocortisone group showed reduced thickness and weight of dorsal skin in mice （all P < 0.01）, numbers of infiltrating lymphocytes and mast cells （all P < 0.01） and levels of IFN-γ, TNF-α, IL-4 and IL-5 in skin lesions （P < 0.05 or 0.01） on day 15 after the start of treatment. The thickness and weight of dorsal skin in mice were significantly decreased in the hydrocortisone group （P < 0.01）, but experienced no significant changes in the Chushizhiyang group compared with the normal control group. Additionally, Chushizhiyang ointment could significantly increase itch thresholds in guinea pigs induced by histamine phosphate （P < 0.01）. Conclusions Chushizhiyang ointment can significantly inhibit DNFB-induced AD in mice, likely by restoring the balance between Th1 and Th2 type cytokines. Moreover, Chushizhiyang ointment could markedly relieve itching induced by histamine phosphate in guinea pigs.