Lysionotin enhances circadian rhythm and accelerates the recovery of DSS-induced colitis in mice by targeting the circadian clock component RORα

Lysionotin enhances circadian rhythm and accelerates the recovery of DSS-induced colitis in mice by targeting the circadian clock component RORα | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 21 October 2025 V1 Latest version Share on Lysionotin enhances circadian rhythm and accelerates the recovery of DSS-induced colitis in mice by targeting the circadian clock component RORα Authors : Caimei Wu , Jiahao Xu , Dihao Xie , Meixue Luo , Simin Zhong , Mengting Zhang , Jianning Liang , Ruoyan Zheng , Shuai Wang , Baojian Wu 0000-0003-4629-5142 , and Danyi Lu 0000-0002-3346-2362 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176106970.02853906/v1 155 views 84 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose : Circadian clock disruptions are implicated in various pathological processes, including inflammatory diseases such as ulcerative colitis (UC). Restoring or enhancing the molecular circadian clock represents a promising therapeutic strategy. Lysionotin (LYS), a natural polymethoxyflavone, was investigated for its potential role in modulating circadian rhythms and mitigating colitis. Experimental Approach : LYS was screened for circadian-amplifying effects using human U2OS cells stably expressing Per2-dLuc or Bmal1-dLuc reporters. Its interaction with RORα was assessed through luciferase reporter assays, cellular thermal shift assays (CETSA), and molecular docking. In vivo efficacy was evaluated in a DSS-induced colitis mouse model, with assessments of disease activity index (DAI), histopathology, cytokine levels, and clock gene expression. In vitro studies using LPS-stimulated DLD-1 cells further examined anti-inflammatory mechanisms and RORα dependency. Key Results : LYS significantly enhanced circadian amplitude in U2OS cells without altering periodicity. It directly bound to RORα, increased its thermostability, and activated BMAL1 transcription in a RORα-dependent manner. In DSS-induced colitis mice, LYS treatment accelerated recovery, reduced DAI scores, improved histopathology, lowered proinflammatory cytokines, and restored expression of circadian clock proteins (e.g., BMAL1, PER2, REV-ERBα). In vitro , LYS suppressed LPS-induced NF-κB activation and cytokine production via RORα. Conclusion and Implications : LYS functions as a novel RORα agonist and circadian enhancer that ameliorates experimental colitis by reinforcing circadian rhythms and suppressing NF-κB-mediated inflammation. These findings support the further development of RORα-targeting polymethoxyflavones as chronotherapeutic agents for inflammatory bowel diseases. Supplementary Material File (lysionotin and colitis-20251010.docx) Download 79.36 KB File (lysionotin and colitis-figures.pdf) Download 1.69 MB Information & Authors Information Version history V1 Version 1 21 October 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Caimei Wu Guangzhou University of Chinese Medicine View all articles by this author Jiahao Xu Guangzhou University of Chinese Medicine View all articles by this author Dihao Xie Guangzhou University of Chinese Medicine View all articles by this author Meixue Luo Guangzhou University of Chinese Medicine View all articles by this author Simin Zhong Guangzhou University of Chinese Medicine View all articles by this author Mengting Zhang Guangzhou University of Chinese Medicine View all articles by this author Jianning Liang Guangzhou University of Chinese Medicine View all articles by this author Ruoyan Zheng Guangzhou University of Chinese Medicine View all articles by this author Shuai Wang Guangzhou University of Chinese Medicine View all articles by this author Baojian Wu 0000-0003-4629-5142 Guangzhou University of Chinese Medicine View all articles by this author Danyi Lu 0000-0002-3346-2362 [email protected] Guangzhou University of Chinese Medicine View all articles by this author Metrics & Citations Metrics Article Usage 155 views 84 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Caimei Wu, Jiahao Xu, Dihao Xie, et al. Lysionotin enhances circadian rhythm and accelerates the recovery of DSS-induced colitis in mice by targeting the circadian clock component RORα. Authorea . 21 October 2025. DOI: https://doi.org/10.22541/au.176106970.02853906/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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