Paeoniflorin-6'-O-benzenesulfonate inhibits dendritic cell metabolism to alleviate autoimmune hepatitis via PI3K-AKT-FoxO1 pathway

Paeoniflorin-6'-O-benzenesulfonate inhibits dendritic cell metabolism to alleviate autoimmune hepatitis via PI3K-AKT-FoxO1 pathway | 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 Search Search ADVANCED SEARCH SCROLL British Journal of Pharmacology This is a preprint and has not been peer reviewed. Data may be preliminary. 12 May 2026 V1 Latest version Share on Paeoniflorin-6'-O-benzenesulfonate inhibits dendritic cell metabolism to alleviate autoimmune hepatitis via PI3K-AKT-FoxO1 pathway Authors : Mengxue Hu [email protected] , Hongwei Zhang [email protected] , Yan Zhang [email protected] , Xiao Jiang [email protected] , Li Cao [email protected] , Xiaoqian Wu [email protected] , Xiaohua Wang [email protected] , Yukun Ma [email protected] , chun wang [email protected] , Jingyu Chen [email protected] , Wei Wei 0000-0002-3117-9598 [email protected] , and Tingting Liu [email protected] Authors Info & Affiliations https://doi.org/10.22541/authorea.15003100/v1 20 views 8 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Aims: To investigate the therapeutic effects and molecular mechanism of paeoniflorin-6'-O-benzenesulfonate (CP-25) in autoimmune hepatitis (AIH). Methods: A murine model of AIH was established by dendritic cells (DCs) loaded with hepatocellular carcinoma cells (Hepa1-6). The specific regulation of CP-25 to DCs was tested by incubating DCs with CP-25 in vitro before loading with Hepa1-6 to vaccinate mice. Results: CP-25 alleviated liver injury and inhibited inflammatory infiltration in AIH mice. CP-25 decreased the levels of the proinflammatory cytokines, while promoting the secretion of the anti-inflammatory cytokines. CP-25 downregulated MHC-II, CD86, and CCR7 in bone marrow (BM) DCs and hepatic DCs. In addition, CP-25 upregulated PD-L1 in BMDCs, which increased the regulatory T cells (T regs) and decreased the differentiation of CD8 +T cells in AIH. Pre-treatment DCs with CP-25 also markedly reduced hepatic injury, DC mature and T cell responses. In terms of mechanism, CP-25 suppressed non-esterified fatty acids secretion (NEFA) secretion, glucose uptake, and reduced mitochondrial membrane potential (MMP) and reactive oxygen (ROS) levels in BMDCs, which indicating that CP-25 regulated DC metabolism and function. CP-25 reduced the total protein and phosphorylation levels of the metabolism-related PI3K-AKT pathway significantly. Subsequently, the intracellular total level of forkhead box protein O1 (FoxO1) in BMDCs from AIH mice was elevated. CP-25 reduced the cytoplasmic level of FoxO1 in BMDCs, and promoted its nuclear translocation, thereby maintaining BMDCs in an immature state. Conclusion: CP-25 treatment elicits immunosuppression against AIH by targeting DCs and inhibiting metabolism-related PI3K-AKT-FoxO1 pathway, and thereby disrupts DC-induced cross-priming of T cell responses. Information & Authors Information Version history V1 Version 1 12 May 2026 Collection British Journal of Pharmacology Authors Affiliations Mengxue Hu [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Hongwei Zhang [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Yan Zhang [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Xiao Jiang [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Li Cao [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Xiaoqian Wu [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Xiaohua Wang [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Yukun Ma [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author chun wang [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Jingyu Chen [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Wei Wei 0000-0002-3117-9598 [email protected] The First Affiliated Hospital of Anhui Medical University, Hefei, China, 230022 View all articles by this author Tingting Liu [email protected] View all articles by this author Metrics & Citations Metrics Article Usage 20 views 8 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Mengxue Hu, Hongwei Zhang, Yan Zhang, et al. Paeoniflorin-6'-O-benzenesulfonate inhibits dendritic cell metabolism to alleviate autoimmune hepatitis via PI3K-AKT-FoxO1 pathway. Authorea . 12 May 2026. DOI: https://doi.org/10.22541/authorea.15003100/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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