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Sophora flavescens Alt. (S. flavescens) has been widely acknowledged in the prevention and treatment of psoriasis. Kushenol F (KSCF) is a natural isopentenyl flavonoid extracted from the root of S. flavescens. We aimed to investigate the effect and mechanism of KSCF on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. A mouse model of psoriasis was induced with 5% IMQ for 5 days, and the mice were given KSCF dermally for 5 days. Changes in skin morphology, the psoriasis area, the severity index (PASI), and inflammatory factors of psoriasis-like skin lesions were evaluated. Metabolites in the psoriasis-like skin lesions were analyzed with ultra-high-performance liquid chromatography\/mass spectrometry followed by a multivariate statistical analysis to identify the differential metabolites and metabolic pathway. The results of the present study confirmed that KSCF significantly reduced PASI scores, epidermal thickening, and epidermal cell proliferation and differentiation. KSCF also reduced the levels of interleukin (IL)-1\u03b2, IL-6, IL-8, IL-17A, IL-22, IL-23, and tumor necrosis factor (TNF)-\u03b1 in the injured skin tissues while increasing IL-10 content. KSCF significantly regulated metabolites in the skin samples, and a total of 161 significant metabolites were identified. These differential metabolites involved sphingolipid and linoleic acid metabolism and steroid hormone biosynthesis. Collectively, KSCF inhibited the inflammatory response to prevent IMQ-induced psoriasis-like skin lesions in mice by call-backing the levels of 161 endogenous metabolites and affecting their related metabolic pathways. KSCF has the potential to be developed as a topical drug for treating psoriasis symptoms.<\/jats:p>","DOI":"10.3390\/molecules29112410","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T05:40:47Z","timestamp":1716270047000},"page":"2410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolic Profiling for Unveiling Mechanisms of Kushenol F against Imiquimod-Induced Psoriasis with UHPLC\/MS Analysis"],"prefix":"10.3390","volume":"29","author":[{"given":"Xingxin","family":"Yang","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoli","family":"Cheng","sequence":"additional","affiliation":[{"name":"Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunqing","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Ao","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"He","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqin","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311403, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/jdv.18044","article-title":"Psoriasis and metabolic syndrome: Implications for the management and treatment of psoriasis","volume":"36","author":"Wu","year":"2022","journal-title":"J. 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