Huaiqihuang Alleviates Imiquimod-Induced Psoriasis-Like Skin Lesions and Depressive-Like Behaviors in Mice.

OBJECTIVE: Depression is a significant comorbidity of psoriasis, prompting an exploration of the potential use of traditional Chinese medicine for the concurrent treatment of both conditions. This study aimed to investigate the effects of Huaiqihuang (HQH) on psoriasis and its comorbid depressive-like behavior in a murine model. METHODS: We utilized an imiquimod (IMQ)-induced psoriasis-like model to mimic psoriasis and concurrent depression. The mice received oral HQH extract, and subsequent assessments were performed to monitor changes in skin lesions, inflammatory cells, and depressive behaviors. A network pharmacology approach was used to identify target genes for protein‒protein interaction analysis, and potential signaling pathways were suggested. Based on the above prediction results, we investigated the effects of HQH on Th17 cell levels in the brains, skin-draining lymph nodes, and spleens of model mice to elucidate the underlying mechanisms. RESULTS: Our results revealed a significant reduction in the mouse skin PASI score and pathological score following HQH treatment. Furthermore, HQH had inhibitory effects on CD3+ T-cell infiltration and epidermal proliferation, as supported by Ki67 staining in skin lesions. Additionally, HQH ameliorated weight loss in mice following IMQ-induced modeling and improved depressive-like behavior, as assessed by open field and swimming experiments. The network pharmacology approach predicted the importance of the TNF and IL-17 signaling pathways in the intervention of psoriasis comorbid with depression by HQH. Subsequent experimental validation demonstrated that HQH reduced the proportion of Th17 cells in the spleen, draining lymph nodes, and brain tissues of the mice. CONCLUSIONS: HQH reduced psoriasis skin lesions, relieved depressive-like behaviors and decreased the abundance of Th17 cells in the spleen, lymph nodes, and brain, suggesting the promise of traditional Chinese medicine for managing psoriasis and its comorbidities by targeting Th17 cells.