Abstract
Lanatoside C (LanaC), a cardiac glycoside, has been reported to possess therapeutic potential in acute intestinal inflammation; however, its in vivo effects on ulcerative colitis (UC) remain incompletely understood. In this study, we demonstrated that LanaC effectively attenuates DSS-induced colitis in mice by reducing inflammation, mitigating epithelial damage, and preserving barrier integrity. Mechanistically, LanaC treatment was associated with reduced macrophage infiltration in the colon and spleen, suppression of pro-inflammatory M1 macrophage markers, and enhancement of M2-associated markers. In vitro, LanaC inhibited LPS-induced M1 polarization and pro-inflammatory cytokine production in BMDMs, while promoting IL-4-driven M2 polarization and anti-inflammatory cytokine expression. These effects were accompanied by attenuation of STAT1/STAT3 signaling and enhancement of STAT6 activation, suggesting a selective reprogramming of macrophage responses. Collectively, these findings reveal that LanaC alleviates DSS-induced colitis, at least in part, through regulating macrophage infiltration and repolarization supporting its potential as a macrophage-targeted therapeutic candidate in UC.
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No datasets were generated or analysed during the current study. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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Funding
This study was supported by the National Natural Science Foundation of China (T2341019), NSFC Guangdong Joint Fund (U1132001), General Program of the National Natural Science Foundation of China (82174243 and 82204948), Natural Science Foundation of Guangdong Province, China (2023A1515110757), Guangzhou Science and Technology Plan Project (2024B03J1343), Major Sci-entific and Technological Project of Guangzhou Municipal Health Commission (20252D003), Re-search Project of Traditional Chinese Medicine Bureau of Guangdong Province (20241208), Gen-eral project of Beijing Natural Science Foundation (7242227), Fundamental Research Funds for the Central Universities (BZY-JMZY-2022-001 and 2023-JYB-JBZD-009), High-level Key Discipline of the National Administration of Traditional Chinese Medicine-Traditional Chinese Constitutional Medicine (zyyzdxk-2023251), Major Science and Technology Special Projects in Hubei Province (2023BCA005), and the Chief Scientist Research Project of Hubei Shizhen Laboratory (HSL2024SX0002).
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All authors contributed to the conception and design of the study. LY and HZ conceived and designed the research. LY, HZ, and JL performed all experiments. LY and JL analyzed the data and prepared the figures. LY, HZ, and JW interpreted the experimental results and drafted the manuscript. XZ and JW were responsible for project administration and funding acquisition. All authors reviewed the manuscript.
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Yu, L., Liu, J., Zhao, X. et al. Lanatoside C ameliorates DSS-induced colitis with improved intestinal barrier integrity and reduced M1 macrophage polarization. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37484-0
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DOI: https://doi.org/10.1038/s41598-026-37484-0


