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Recently, mesenchymal stem cells (MSCs) have emerged as a promising candidate for IBD treatment, with energy metabolism playing a critical role. Berberine (BBR), a natural extract from Berberidaceae plants, has been shown to modulate various cell functions by reprogramming metabolism in immune\u2010related diseases. This study aims to investigate the influence of BBR on the therapeutic effectiveness of MSCs in colitis. Using the colitis mice model, we compared the therapeutic effects of BBR treated MSCs (MSC\n                    <jats:sub>BBR<\/jats:sub>\n                    ) and untreated MSCs by evaluating colon length, Disease Activity Index, and histopathological change. Various methods were employed to detect the differences of MSC\n                    <jats:sub>BBR<\/jats:sub>\n                    and MSCs, including seahorse analysis for energy metabolism, RNA\u2010seq and qPCR for gene transcription, western blotting for protein expression, flow cytometry for phenotypic analysis, and cytokine production. Our results revealed that BBR treatment activated the AMPK signaling pathway, upregulated the expression of glucose transporter 1 (GLUT1), and promoted aerobic glycolysis in MSCs. Comparing to MSCs, MSC\n                    <jats:sub>BBR<\/jats:sub>\n                    exhibited the increased expression of tumor necrosis factor\u2010stimulated gene\u20106 (TSG\u20106), enhanced immunomodulatory function and superior therapeutic efficacy. Inhibition of either glycolysis or TSG\u20106 expression impaired the therapeutic effect of MSC\n                    <jats:sub>BBR<\/jats:sub>\n                    , while overexpression of GLUT1 or TSG\u20106 obviously improved the therapeutic efficacy of MSCs. BBR treatment improved the therapeutic effect of MSCs in colitis by promoting aerobic glycolysis, providing a safe new approach for optimizing MSCs\u2010based therapy in IBD through reprogramming energy metabolism.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70372","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:45:45Z","timestamp":1779673545000},"page":"5193-5207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Berberine Improved the Therapeutic Efficacy of\n                    <scp>UC<\/scp>\n                    \u2010\n                    <scp>MSCs<\/scp>\n                    for\n                    <scp>DSS<\/scp>\n                    \u2010Induced Colitis via Aerobic Glycolysis"],"prefix":"10.1002","volume":"40","author":[{"given":"Mengye","family":"Wu","sequence":"first","affiliation":[{"name":"The Biotherapy Center, The Third Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiping","family":"Li","sequence":"additional","affiliation":[{"name":"The Biotherapy Center, The Third Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqi","family":"Feng","sequence":"additional","affiliation":[{"name":"Center for Stem Cells Translational Medicine Shenzhen Qianhai Shekou Free Trade Zone Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Stem Cells Translational Medicine Shenzhen Qianhai Shekou Free Trade Zone Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Fang","sequence":"additional","affiliation":[{"name":"Center for Stem Cells Translational Medicine Shenzhen Qianhai Shekou Free Trade Zone Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghai","family":"Lian","sequence":"additional","affiliation":[{"name":"Cell\u2010Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Stem Cells Translational Medicine Shenzhen Qianhai Shekou Free Trade Zone Hospital  Shenzhen Guangdong 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