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Currently, about 10% of adults worldwide are affected by this disease. In recent years, significant progress has been made in the field of renal fibrosis treatment, with both traditional drugs and innovative therapies showing new hope. In this study, we propose a novel therapeutic strategy for renal fibrosis based on the traditional Chinese medicine concept of \u201cmedicinal and edible homology\u201d. This involves the use of a compound formulation comprising red ginseng, dandelion, and oyster shell, and evaluating its therapeutic effect on renal fibrosis through the colon administration route. Through integrated network pharmacology and molecular docking analyses, we identified AKT1, JUN, TNF, HSP90AA1, and IL\u20106 as core targets, with the PI3K\/AKT signaling pathway playing a key role. Colon administration of the formulation significantly restored intestinal barrier function by upregulating tight junction proteins ZO\u20101 and occludin, thereby reducing circulating endotoxin (LPS) and systemic inflammatory markers (IL\u20106, IL\u20101\u03b2). Concurrently, the treatment intervened in the renal PI3K\/AKT pathway, upregulated expressions of PI3KR1, PKCa, and AKT1\/2\/3, improved renal function (reduced creatinine and urea nitrogen), and ameliorated fibrosis markers (reduced fibronectin and \u03b1\u2010SMA, increased E\u2010cadherin). These findings demonstrate that the medicinal\u2010edible homologous formulation alleviates renal fibrosis via modulation of the gut\u2013kidney axis, combining intestinal barrier repair with suppression of pro\u2010fibrotic signaling. This study supports the use of colon\u2010delivered traditional Chinese medicine as a promising therapeutic strategy for renal fibrosis.<\/jats:p>","DOI":"10.1002\/fsn3.71186","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:42:27Z","timestamp":1763120547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A New Strategy for Treating Renal Fibrosis Based on a Drug\u2010Food Homogeneous Formula of Traditional Chinese Medicine"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1283-3322","authenticated-orcid":false,"given":"Gao","family":"Zitian","sequence":"first","affiliation":[{"name":"Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemical and Molecular Engineering East China University of 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