She-Chuang-Si-Wu-Tang Alleviates Inflammation and Itching Symptoms in a Psoriasis Mouse Model by Regulating the Th17/IL-17 Axis via the STAT3/MAPK Pathways

Weixiong Chen,1,2,* Jianqiang Liang,3,* Shuang He,1,4,5 Qingsong Liang,1,4,5 Wenting Tian,6 Aobo Lu,1 Demin Li,1 Zhicheng Huang,1 Guanyi Wu1,4,5 1College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China; 2School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, People’s Republic of China; 3Department of Dermatology, the First People’s Hospital of Yulin, Yulin, Guangxi, 537000, People’s Republic of China; 4Key Laboratory for Complementary and Alternative Medicine Experimental Animal Models of Guangxi, Nanning, Guangxi, 530299, People’s Republic of China; 5Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Nanning, Guangxi, 530299, People’s Republic of China; 6College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guanyi Wu, College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530299, People’s Republic of China, Email [email protected]: Psoriasis is an immune-related disorder characterized by silver scales, epidermis thickness, and itching. She-Chuang-Si-Wu-Tang (SSWT), a traditional Chinese medicine decoction, has been used clinically for 400 years. Although it benefits psoriasis treatment, the mechanism of action is still unclear. This study explores SSWT’s molecular mechanism in treating psoriasis through network pharmacology analysis and experiments.Methods: We identified relevant SSWT and psoriasis targets using network pharmacology and conducted SSWT quality control with high-performance liquid chromatography (HPLC). A mouse model of psoriasis was established using imiquimod (IMQ), with the drug administered continuously for seven days, spanning an eight-day period. During the experiment, we observed spontaneous scratching behaviors and assessed the Psoriasis Area and Severity Index (PASI) scores. At the conclusion of the experiment, we examined skin tissue pathology under an optical microscope and measured epidermal thickness. Additionally, we used enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure interleukin (IL)-23, IL-17A, IL-17F, and interferon (IFN)-γ levels in the mice’s serum and their mRNA expression in the skin. Western blot analysis was conducted to assess protein levels related to signaling pathways.Results: Results indicate that SSWT may target IL-17 signaling pathways and T helper (Th) 17 cell differentiation, as predicted by network pharmacology. SSWT significantly improved the PASI and Baker scores, reduced epidermal thickness, and decreased spontaneous scratching in IMQ-induced mice. Additionally, SSWT treatment significantly lowered the concentrations of inflammatory factors in the serum and skin lesions, as well as mRNA expression levels, compared to the IMQ group. Furthermore, SSWT significantly inhibited the phosphorylation of both the signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) pathways.Conclusion: In summary, this study unveiled the potential anti-psoriatic mechanism of SSWT, offering new evidence for its clinical application. Keywords: She-Chuang-Si-Wu-Tang, psoriasis, inflammation, itch, STAT3, MAPK