{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:38:22Z","timestamp":1790786302403,"version":"4.1.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Psoriasis is a common autoimmune and chronic inflammatory dermatological disease that is mainly associated with aberrant immune response and oxidative stress (OS). OS, a crucial pathogenic factor in psoriasis, contributes to psoriasis-like inflammation mediated by the IL-23\/IL-17 inflammatory axis. Sleep disturbances (SDs), highly prevalent in patients with psoriasis, exacerbate the condition by disrupting circadian rhythms and reducing melatonin levels, thus promoting OS and inflammation. Xiaoyin-Anshen formula (XYAS), a traditional Chinese medicine (TCM) formula, is composed of the Liangxue-Jiedu (LXJD) and Qingxin-Anshen (QXAS) TCM compounds and has been demonstrated to be effective in treating psoriasis complicated by SDs. However, its exact pharmacological mechanism remains uncertain. Thus, this study used animal experiments to verify whether XYAS can exert therapeutic effects on the disease by regulating melatonin (MLT) levels, protecting against OS, and inhibiting psoriasis-like skin inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A mouse model for psoriasis combined with SDs was established by smearing 62.5\u00a0mg of 5% imiquimod (IMQ) cream for seven consecutive days, along with a daily injection of p-chlorophenyl alanine (PCPA) solution at a dosage of 300\u00a0mg\/kg at days 6\u20137. The IMQ cream was continued to be used for maintaining the model at days 8\u201314. Mice were randomly divided into groups: control, model, MLT, XYAS, LXJD, QXAS. Each group was treated according to its designation at days 8\u201314, receiving either an oral gavage of XYAS\/LXJD\/QXAS solution at a dosage of 2\u00a0mL\/100\u00a0g per day, or a daily injection of MLT solution at a concentration of 0.25\u00a0mg\/mL, with a dosage of 5\u00a0mg\/kg. Immunohistological analysis, pentobarbital-induced sleep test, Western blotting, and enzyme-linked immunosorbent assay (ELISA) were performed to assess and compare pathological features, sleep conditions, localization and\/or levels of manganese-dependent superoxide dismutase (mnSOD), mitochondrial cytochrome c (Cyt-C), MLT, retinoid-related orphan nuclear receptor-\u03b1 (ROR\u03b1), and pro-inflammatory cytokines interleukin (IL)-6, IL-17A, and tumor necrosis factor-alpha (TNF-\u03b1) among groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MLT, XYAS, LXJD, and QXAS exhibited varying therapeutic effects on ROR\u03b1 regulation, OS inhibition, mitochondrial protection, and anti-inflammation. Compared to the model, the lesion severity\/thickness and serum IL-6, IL-17A, and TNF-\u03b1 levels were gradually reduced in the MLT, QXAS, LXJD, and XYAS. However, no statistical difference in TNF-\u03b1 levels was identified between the MLT and the model groups. Additionally, skin MLT levels gradually increased in the MLT, QXAS, and XYAS groups, while ROR\u03b1 levels gradually increased in the MLT, QXAS, LXJD, and XYAS groups. All treatments increased mnSOD levels and reduced Cyt-C levels in skin lesions, with XYAS showing the most significant changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>XYAS may treat psoriasis complicated by SDs through two main mechanisms: (1) Improving melatonin-ROR\u03b1 axis in the skin can lead to an increase in mnSOD and a reduction in Cyt-C levels, which provide protection against oxidative stress, mitochondrial damage, and psoriatic inflammation. (2) Reducing IL-6, IL-17A, and TNF-\u03b1 production to suppress IL-23\/Th17 pro-inflammatory signaling axis and epidermal hyperplasia in psoriasis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2024.1427985","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T04:40:39Z","timestamp":1727757639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Xiaoyin-anshen formula alleviates psoriasis complicated by sleep disturbances by regulating melatonin, antioxidant enzymes, and pro-inflammatory cytokines in mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Zebing","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwu","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"359","DOI":"10.3390\/antiox11020359","article-title":"Interactive effects of melatonin and nitrogen improve drought tolerance of maize seedlings by regulating growth and physiochemical attributes","volume":"11","author":"Ahmad","year":"2022","journal-title":"Antioxidants Basel, Switz."},{"key":"B2","doi-asserted-by":"publisher","first-page":"82","DOI":"10.2174\/1574886315666200128095958","article-title":"Treatment of psoriasis: a comprehensive review of entire therapies","volume":"15","author":"Bakshi","year":"2020","journal-title":"Curr. drug Saf."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3618","DOI":"10.2174\/1381612829666221201161636","article-title":"Role of oxidative stress and inflammation in insomnia sleep disorder and cardiovascular diseases: herbal antioxidants and anti-inflammatory coupled with insomnia detection using machine learning","volume":"28","author":"Bin Heyat","year":"2022","journal-title":"Curr. 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