Academic Journal
Metabolic-circadian reprogramming mediates epithelial barrier destabilization during Euphorbia fischeriana toxicity and its mitigation by traditional milk processing.
| Τίτλος: | Metabolic-circadian reprogramming mediates epithelial barrier destabilization during Euphorbia fischeriana toxicity and its mitigation by traditional milk processing. |
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| Συγγραφείς: | Yu R; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: yurl0024@163.com., Zhang S; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: zsr642202893@163.com., Jiang E; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: jiangenci@163.com., Wang E; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: wangerrui2000@163.com., Cheng Z; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: czc0221@163.com., Yu H; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; National Base of State Ministry of Education for Inheritance of Chinese Medicine Processing Technology, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Key Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: yhl@njucm.edu.cn., Cao J; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: 20223109@njucm.edu.cn., Liu B; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; National Base of State Ministry of Education for Inheritance of Chinese Medicine Processing Technology, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Key Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: bbliu@njucm.edu.cn., Lai Y; The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: laiyy@njucm.edu.cn., Wang X; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: xinzhiwang@njucm.edu.cn., Wu H; College of Pharmacy, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; National Base of State Ministry of Education for Inheritance of Chinese Medicine Processing Technology, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Key Laboratory of State Administration of TCM for Standardization of Chinese Medicine Processing, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China; Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Qixia District, Xianlin Road No. 138, Nanjing, 210023, China. Electronic address: whao5795@njucm.edu.cn. |
| Πηγή: | Journal of ethnopharmacology [J Ethnopharmacol] 2026 Oct 28; Vol. 369, pp. 121861. Date of Electronic Publication: 2026 May 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Sequoia Country of Publication: Ireland NLM ID: 7903310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7573 (Electronic) Linking ISSN: 03788741 NLM ISO Abbreviation: J Ethnopharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier Sequoia Original Publication: Lausanne, Elsevier Sequoia. |
| Ιατρικοί όροι (MeSH): | Euphorbia*/chemistry , Euphorbia*/toxicity , Plant Extracts*/toxicity , Circadian Rhythm*/drug effects , Intestinal Mucosa*/drug effects , Intestinal Mucosa*/metabolism, Tight Junctions/drug effects ; Tight Junctions/metabolism ; Animals ; Zebrafish ; Intestinal Barrier Function ; Humans ; Mice ; Milk ; Food, Processed ; Plant Roots |
| Περίληψη: | Ethnopharmacological Relevance: EUPHORBIAE EBRACTEOLATAE RADIX (Langdu), the dried root of Euphorbia fischeriana Steud. (E. fischeriana), has been widely used in Mongolian and traditional Chinese medicine for the treatment of inflammatory disorders and malignancies. However, its clinical application is limited by its gastrointestinal toxicity. Milk processing is traditionally used to reduce toxicity, but the underlying mechanisms remain unclear. Aim of the Study: To investigate the mechanisms underlying E. fischeriana-induced intestinal toxicity and to evaluate the effects of traditional milk processing. Materials and Methods: Zebrafish and mouse models were used to assess intestinal alterations induced by E. fischeriana extract. Transcriptomic and metabolomic analyses were performed to characterize molecular changes. Barrier integrity was evaluated by tight junction gene expression and organoid permeability assays. Circadian rhythmicity was analyzed in HT-29 cells synchronized with dexamethasone. Results: Exposure to the extract of raw E. fischeriana (EEF) accelerated gastrointestinal transit in zebrafish and induced villus shortening and epithelial disorganization. Multi-omics analysis revealed profound metabolic reprogramming, including suppression of mitochondrial energy and lipid metabolism, together with perturbation of nitrogen-related pathways, accompanied by circadian disruption and epithelial remodeling. Functionally, EEF reduced Per3 oscillatory amplitude and downregulated tight junction genes (Cldn3, Cldn4, and Cldn15), leading to increased epithelial permeability. Conversely, the extract of milk-processed E. fischeriana (EPEF) partially alleviated intestinal structural damage and restored metabolic pathways, but circadian rhythmicity remained incompletely recovered. Conclusions: E. fischeriana disrupts intestinal metabolic and circadian coordination, leading to epithelial barrier dysfunction. Milk processing partially mitigates intestinal metabolic disturbance and structural injury, but fails to fully restore circadian regulation. These findings provide mechanistic insight into the intestinal toxicity of E. fischeriana and the detoxification mechanism of traditional milk processing. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Circadian rhythm; Epithelial barrier; Euphorbia fischeriana; Gastrointestinal toxicity; Milk processing |
| Substance Nomenclature: | 0 (Plant Extracts) |
| Entry Date(s): | Date Created: 20260516 Date Completed: 20260613 Latest Revision: 20260613 |
| Update Code: | 20260615 |
| DOI: | 10.1016/j.jep.2026.121861 |
| PMID: | 42142552 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-7573 |
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| DOI: | 10.1016/j.jep.2026.121861 |