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Emerging research has underscored the potential of plant\u2010derived exosomes for UC treatment. In this study, it is found that Centella Asiatica\u2010derived exosomes (CAEs) have anti\u2010colitis effects. CAEs selectively accumulate in inflamed colons, enabling targeted delivery of RNA cargos. MicroRNA (miRNA)\u2010enriched CAEs not only mitigate inflammation but also facilitate the reconstitution of a balanced gut microbiota, characterized by a deceased abundance of pathogenic bacteria (e.g.,\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    ), as well as regulating 880 serum metabolites. Furthermore, the results indicate the remarkable impact of specific miRNAs from CAEs, such as\n                    <jats:italic>aof\u2010miR396b<\/jats:italic>\n                    and\n                    <jats:italic>fve\u2010miR396c\u20103p<\/jats:italic>\n                    , on\n                    <jats:italic>Peak1<\/jats:italic>\n                    target. CAEs attenuate inflammatory responses and enhance the functions of immune cells in the intestinal milieu. Importantly, the safety profile of CAEs is exemplary, with no discernible adverse effects observed in both in vitro and in vivo assays. This study posits plant\u2010derived exosomes as a potent, targeted, and safe therapeutic modality for UC, representing an alternative to conventional treatments by leveraging the inherent bioactive properties of botanically derived nanovesicles and the cross\u2010kingdom regulatory potential of plant\u2010derived miRNAs on mammalian genes.\n                  <\/jats:p>","DOI":"10.1002\/advs.202505921","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T06:47:10Z","timestamp":1758782830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["MicroRNA\u2010Enriched Plant\u2010Derived Exosomes Alleviate Colitis by Modulating Systemic Immunity, Metabolic Homeostasis, and Gut Microbiota"],"prefix":"10.1002","volume":"12","author":[{"given":"Ruipeng","family":"Shi","sequence":"first","affiliation":[{"name":"Macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Pharmacy Lanzhou University  Lanzhou 730000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haochun","family":"Jin","sequence":"additional","affiliation":[{"name":"Macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sio I","family":"Chan","sequence":"additional","affiliation":[{"name":"Macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Modern Research Center for Traditional Chinese Medicine Beijing Research Institute of Chinese Medicine Beijing University of Chinese Medicine  Beijing 102401 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si San","family":"Lei","sequence":"additional","affiliation":[{"name":"Macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhen","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Zhuhai Campus of Zunyi Medical University  Zhuhai 519041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitao","family":"Wang","sequence":"additional","affiliation":[{"name":"Macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8649-5531","authenticated-orcid":false,"given":"Dong\u2010Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"New York College of Traditional Chinese Medicine  Mineola New York 11501 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangfeng","family":"Zhong","sequence":"additional","affiliation":[{"name":"Macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1132"},{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.08.003"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.208"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0268-7"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202409138"},{"key":"e_1_2_10_3_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48128-0"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abf0677"},{"key":"e_1_2_10_4_2","first-page":"472","volume":"10","author":"Vila A. 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