{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:37:08Z","timestamp":1789105028812,"version":"build-2803163510"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Oxidative stress is a key pathological cause of intestinal epithelial injury and related intestinal diseases. Chlorogenic acid (CGA), a natural polyphenol, has notable antioxidant activity. This study explored the multi-target protective effects of CGA on intestinal epithelial cells and mouse intestinal tissue against oxidative injury, as well as its underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Network pharmacology was applied to screen core targets and enriched pathways of CGA against oxidative stress. H\u2082O\u2082-induced MODE-K cell oxidative damage model and LPS-induced mouse intestinal injury model were constructed. CCK-8, biochemical detection, qPCR, molecular docking, Western blotting and histopathological assay were performed to verify the protective effects and related signaling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Network pharmacology predicted PI3K\/Akt and Nrf2\/HO-1 pathways as crucial targets.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , CGA elevated cell viability, reduced oxidative injury markers, upregulated antioxidant factors, and regulated apoptosis-related proteins. CGA blocked Keap1-Nrf2 binding, activated Nrf2\/HO-1 and promoted Akt phosphorylation.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , CGA alleviated LPS-induced intestinal pathological injury, while PI3K inhibitor LY294002 reversed its protective effects, confirming the critical role of PI3K\/Akt-Nrf2\/HO-1 axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CGA exerts multi-target antioxidant and intestinal protective effects by inhibiting Keap1-Nrf2 interaction and activating PI3K\/Akt-Nrf2\/HO-1 signaling axis, mitigating intestinal oxidative injury. Our findings provide a mechanistic basis for the application of CGA as a functional food ingredient or dietary intervention to alleviate intestinal oxidative stress in livestock.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1870702","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:25:42Z","timestamp":1783657542000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Protective effects of chlorogenic acid against LPS-induced intestinal oxidative injury in mice via activation of the PI3K\/Akt-Nrf2\/HO-1 signaling axis"],"prefix":"10.3389","volume":"13","author":[{"given":"Ying","family":"He","sequence":"first","affiliation":[{"name":"Department of Biological and Food Engineering, Lyuliang University","place":["Lvliang, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biological and Food Engineering, Lyuliang University","place":["Lvliang, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biological and Food Engineering, Lyuliang University","place":["Lvliang, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological and Food Engineering, Lyuliang University","place":["Lvliang, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiping","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biological and Food Engineering, Lyuliang University","place":["Lvliang, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"5938","DOI":"10.3390\/ijms23115938","article-title":"An overview of oxidative stress, Neuroinflammation, and neurodegenerative diseases","volume":"23","author":"Teleanu","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.3390\/antiox12081543","article-title":"From challenge to opportunity: addressing oxidative stress in animal husbandry","volume":"12","author":"Zhang","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3390\/nu15010198","article-title":"Glutathione protects against paraquat-induced oxidative stress by regulating intestinal barrier, antioxidant capacity, and CAR signaling pathway in weaned piglets","volume":"15","author":"Xiang","year":"2022","journal-title":"Nutrients"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/6175804","article-title":"ROS generation and antioxidant defense Systems in Normal and Malignant Cells","volume":"2019","author":"Snezhkina","year":"2019","journal-title":"Oxidative Med Cell Longev"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"924","DOI":"10.3390\/nu16070924","article-title":"Chlorogenic acid: a systematic review on the biological functions, mechanistic actions, and therapeutic potentials","volume":"16","author":"Nguyen","year":"2024","journal-title":"Nutrients"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"101960","DOI":"10.1016\/j.tice.2022.101960","article-title":"Efficacy of chlorogenic acid against ethylene glycol-induced renal stone model: the role of NFKB-RUNX2-AP1-OSTERIX signaling pathway","volume":"79","author":"Hoseinynejad","year":"2022","journal-title":"Tissue Cell"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"103586","DOI":"10.1016\/j.psj.2024.103586","article-title":"Chlorogenic acid ameliorates intestinal inflammation by inhibiting NF-\u03baB and endoplasmic reticulum stress in lipopolysaccharide-challenged broilers","volume":"103","author":"Liu","year":"2024","journal-title":"Poult Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"BSR20221375","DOI":"10.1042\/BSR20221375","article-title":"Exploring the mechanism of Cassiae semen in regulating lipid metabolism through network pharmacology and experimental validation","volume":"43","author":"Huang","year":"2023","journal-title":"Biosci Rep"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12906-022-03822-8","article-title":"Anti-colorectal cancer of Ardisia gigantifolia Stapf. 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