{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:37:01Z","timestamp":1785548221494,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31972589"],"award-info":[{"award-number":["31972589"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["31972589"],"award-info":[{"award-number":["31972589"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Lipopolysaccharide (LPS) is an endotoxin that induces immune and inflammatory responses in the rumen epithelium of dairy cows. It is well-known that flavonoid phloretin (PT) exhibits anti-oxidative, anti-inflammatory and antibacterial activity. The aim of this research was to explore whether PT could decrease LPS-induced damage to bovine rumen epithelial cells (BRECs) and its molecular mechanisms of potential protective efficacy. BRECs were pretreated with PT for 2 h and then stimulated with LPS for the assessment of various response indicators. The results showed that 100 \u00b5M PT had no significant effect on the viability of 10 \u00b5g\/mL LPS-induced BRECs, and this dose was used in follow-up studies. The results showed that PT pre-relieved the decline in LPS-induced antioxidant indicators (T-AOC and GSH-PX). PT pretreatment resulted in decreased interleukin-1\u03b2 (IL-1\u03b2), IL-6, IL-8, tumor necrosis factor-\u03b1 (TNF-\u03b1) and chemokines (CCL2, CCL5, CCL20) expression. The underlying mechanisms explored reveal that PT may contribute to inflammatory responses by regulating Toll-like receptor 4 (TLR4), nuclear transcription factor-\u03baB p65 (NF-\u03baB p65), and ERK1\/2 (p42\/44) signaling pathways. Moreover, further studies found that LPS-induced BRECs showed decreased expression of claudin-related genes (ZO-1, Occludin); these were attenuated by pretreatment with PT. These results suggest that PT enhances the antioxidant properties of BRECs during inflammation, reduces gene expression of pro-inflammatory cytokines and chemokines, and enhances barrier function. Overall, the results suggest that PT (at least in vitro) offers some protective effect against LPS-induced ruminal epithelial inflammation. Further in vivo studies should be conducted to identify strategies for the prevention and amelioration of short acute rumen acidosis (SARA) in dairy cows using PT.<\/jats:p>","DOI":"10.3390\/toxins14050337","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T23:08:36Z","timestamp":1652396916000},"page":"337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Phloretin Protects Bovine Rumen Epithelial Cells from LPS-Induced Injury"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-7512","authenticated-orcid":false,"given":"Kexin","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Lei","sequence":"additional","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4533-101X","authenticated-orcid":false,"given":"Maocheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8078-4209","authenticated-orcid":false,"given":"Qianbo","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-0637","authenticated-orcid":false,"given":"Osmond","family":"Datsomor","sequence":"additional","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Zhan","sequence":"additional","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1017\/S1751731120000786","article-title":"Effects of the acid\u2013base treatment of corn on rumen fermentation and microbiota, inflammatory response and growth performance in beef cattle fed high-concentrate diet","volume":"14","author":"Liu","year":"2020","journal-title":"Animal"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114299","DOI":"10.1016\/j.anifeedsci.2019.114299","article-title":"Effects of dietary supplementation of inulin on rumen fermentation and bacterial microbiota, inflammatory response and growth performance in finishing beef steers fed high or low-concentrate diet","volume":"258","author":"Tian","year":"2019","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"856","DOI":"10.3168\/jds.S0022-0302(07)71569-2","article-title":"Ruminal lipopolysaccharide concentration and inflammatory response during grain-induced subacute ruminal acidosis in dairy cows","volume":"90","author":"Gozho","year":"2007","journal-title":"J. Dairy Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1751-0147-53-48","article-title":"Diet-induced bacterial immunogens in the gastrointestinal tract of dairy cows: Impacts on immunity and metabolism","volume":"53","author":"Dong","year":"2011","journal-title":"Acta Vet. Scand."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.biochem.71.110601.135414","article-title":"Lipopolysaccharide endotoxins","volume":"71","author":"Raetz","year":"2002","journal-title":"Annu. Rev. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bertani, B., and Ruiz, N. (2018). Function and biogenesis of lipopolysaccharides. EcoSal Plus, 8.","DOI":"10.1128\/ecosalplus.esp-0001-2018"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Aperce, C., Amachawadi, R., Van Bibber-Krueger, C., Nagaraja, T., Scott, H., Vinasco-Torre, J., and Drouillard, J. (2016). Effects of menthol supplementation in feedlot cattle diets on the fecal prevalence of antimicrobial-resistant Escherichia coli. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168983"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11233","DOI":"10.3168\/jds.2019-16549","article-title":"The effect of J5 bacterins on clinical, behavioral, and antibody response following an Escherichia coli intramammary challenge in dairy cows at peak lactation","volume":"102","author":"Steele","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.5487\/TR.2018.34.1.065","article-title":"Pretreatment of low-dose and super-low-dose LPS on the production of in vitro LPS-induced inflammatory mediators","volume":"34","author":"Chae","year":"2018","journal-title":"Toxicol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.2174\/1389557519666190311154425","article-title":"Pharmacological aspects and potential use of phloretin: A systemic review","volume":"19","author":"Mariadoss","year":"2019","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.molliq.2017.03.098","article-title":"Molecular model and in vitro antioxidant activity of a water-soluble and stable phloretin\/hydroxypropyl-\u03b2-cyclodextrin inclusion complex","volume":"236","author":"Wei","year":"2017","journal-title":"J. Mol. Liq."},{"key":"ref_12","first-page":"6551","article-title":"Anticancer activity of phloretin against human gastric cancer cell lines involves apoptosis, cell cycle arrest, and inhibition of cell invasion and JNK signalling pathway","volume":"24","author":"Xu","year":"2018","journal-title":"Med. Sci. Monit. Int. Med. J. Exp. Clin. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.intimp.2015.04.024","article-title":"Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-\u03baB pathway in the TNF-\u03b1-induced HaCaT human keratinocytes","volume":"27","author":"Huang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s11101-017-9500-x","article-title":"Health effects of phloretin: From chemistry to medicine","volume":"16","author":"Behzad","year":"2017","journal-title":"Phytochem. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"333","DOI":"10.4014\/jmb.1910.10063","article-title":"Phloretin Protects Macrophages from E. Coli-Induced Inflammation through the TLR4 Signaling Pathway","volume":"30","author":"Chauhan","year":"2020","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8601","DOI":"10.3168\/jds.2020-18417","article-title":"The effect of chronic, mild heat stress on metabolic changes of nutrition and adaptations in rumen papillae of lactating dairy cows","volume":"103","author":"Eslamizad","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1002\/mnfr.200800575","article-title":"Influence of apple polyphenols on inflammatory gene expression","volume":"53","author":"Jung","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104489","DOI":"10.1016\/j.phrs.2019.104489","article-title":"Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota","volume":"150","author":"Wu","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cell.2004.07.002","article-title":"Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis","volume":"118","author":"Paglino","year":"2004","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/j.1749-6632.2009.04692.x","article-title":"Phloretin Induces Apoptosis in H-Ras MCF10A Human Breast Tumor Cells through the Activation of p53 via JNK and p38 Mitogen-Activated Protein Kinase Signaling","volume":"1171","author":"Kim","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.tvjl.2007.12.016","article-title":"Subacute ruminal acidosis in dairy cows: The physiological causes, incidence and consequences","volume":"176","author":"Plaizier","year":"2008","journal-title":"Vet. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhao, C., Liu, G., Li, X., Guan, Y., Wang, Y., Yuan, X., Sun, G., Wang, Z., and Li, X. (2018). Inflammatory mechanism of Rumenitis in dairy cows with subacute ruminal acidosis. BMC Vet. Res., 14.","DOI":"10.1186\/s12917-018-1463-7"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/1462-2920.12724","article-title":"Microbiome\u2013metabolome analysis reveals unhealthy alterations in the composition and metabolism of ruminal microbiota with increasing dietary grain in a goat model","volume":"18","author":"Mao","year":"2016","journal-title":"Environ. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.3168\/jds.2018-15243","article-title":"Symposium review: The importance of the ruminal epithelial barrier for a healthy and productive cow","volume":"102","author":"Aschenbach","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.vetimm.2008.10.305","article-title":"Impact of oxidative stress on the health and immune function of dairy cattle","volume":"128","author":"Sordillo","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0074-7696(04)37002-6","article-title":"Free radicals in cell biology","volume":"237","author":"Djordjevic","year":"2004","journal-title":"Int. Rev. Cytol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"114398","DOI":"10.1016\/j.jep.2021.114398","article-title":"Antioxidant capacity of flavonoids from Folium Artemisiae Argyi and the molecular mechanism in Caenorhabditis elegans","volume":"279","author":"Hu","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105298","DOI":"10.1016\/j.micpath.2021.105298","article-title":"Phloretin is protective in a murine salmonella enterica serovar typhimurium infection model","volume":"161","author":"Zhang","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.2337\/diabetes.52.5.1256","article-title":"High glucose-induced expression of proinflammatory cytokine and chemokine genes in monocytic cells","volume":"52","author":"Shanmugam","year":"2003","journal-title":"Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.3389\/fpsyt.2020.561998","article-title":"Nrf2 activators as dietary phytochemicals against oxidative stress, inflammation, and mitochondrial dysfunction in autism spectrum disorders: A systematic review","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.4049\/jimmunol.180.2.1139","article-title":"Differential activation of human TLR4 by Escherichia coli and Shigella flexneri 2a lipopolysaccharide: Combined effects of lipid A acylation state and TLR4 polymorphisms on signaling","volume":"180","author":"Rallabhandi","year":"2008","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1038\/s41598-019-40577-8","article-title":"Development of a novel short 12-meric papiliocin-derived peptide that is effective against Gram-negative sepsis","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_33","first-page":"1","article-title":"The toll-like receptor-4 (TLR-4) pathway and its possible role in the pathogenesis of Escherichia coli mastitis in dairy cattle","volume":"39","author":"Bannerman","year":"2008","journal-title":"Vet. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1128\/CDLI.7.2.161-167.2000","article-title":"Differential induction of complement fragment C5a and inflammatory cytokines during intramammary infections with Escherichia coli and Staphylococcus aureus","volume":"7","author":"Riollet","year":"2000","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_36","first-page":"1","article-title":"Assessment of the immune capacity of mammary epithelial cells: Comparison with mammary tissue after challenge with Escherichia coli","volume":"40","author":"Koczan","year":"2009","journal-title":"Vet. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1136\/gutjnl-2019-319919","article-title":"Location-specific cell identity rather than exposure to GI microbiota defines many innate immune signalling cascades in the gut epithelium","volume":"70","author":"Kayisoglu","year":"2021","journal-title":"Gut"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40104-016-0100-1","article-title":"High-concentrate feeding upregulates the expression of inflammation-related genes in the ruminal epithelium of dairy cattle","volume":"7","author":"Zhang","year":"2016","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, R., Fang, H., Shen, J., Jin, Y., and Zhang, J. (2021). Curcumin Alleviates LPS-Induced Oxidative Stress, Inflammation and Apoptosis in Bovine Mammary Epithelial Cells via the NFE2L2 Signaling Pathway. Toxins, 13.","DOI":"10.3390\/toxins13030208"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.intimp.2016.08.035","article-title":"Phloretin attenuates LPS-induced acute lung injury in mice via modulation of the NF-\u03baB and MAPK pathways","volume":"40","author":"Huang","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1158\/2326-6066.CIR-17-0036","article-title":"Protumor steering of cancer inflammation by p50 NF-\u03baB enhances colorectal cancer progression","volume":"6","author":"Porta","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_42","first-page":"846","article-title":"Expressions and clinicopathologic significance of Id2 and NF-\u03baB\/P65 in gastric cancer","volume":"98","author":"Li","year":"2018","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3020675","DOI":"10.1155\/2018\/3020675","article-title":"Characterization of site-specific phosphorylation of NF-\u03baB p65 in retinal cells in response to high glucose and cytokine polarization","volume":"2018","author":"Shi","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2000658","DOI":"10.1002\/mnfr.202000658","article-title":"Phloretin, an Apple Polyphenol, Inhibits Pathogen-Induced Mucin Overproduction","volume":"65","author":"Birru","year":"2021","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1039\/C8FO01699B","article-title":"The protective role of phloretin against dextran sulfate sodium-induced ulcerative colitis in mice","volume":"10","author":"Zhang","year":"2019","journal-title":"Food Funct."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/35065000","article-title":"Mammalian MAP kinase signalling cascades","volume":"410","author":"Chang","year":"2001","journal-title":"Nature"},{"key":"ref_47","first-page":"308","article-title":"Phloretin flavonoid exhibits selective antiproliferative activity in doxorubicin-resistant gastric cancer cells by inducing autophagy, inhibiting cell migration and invasion, cell cycle arrest and targeting ERK1\/2 MAP pathway","volume":"25","author":"You","year":"2020","journal-title":"J. BUON"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.3389\/fphys.2019.01305","article-title":"The regulation of ruminal short-chain fatty acids on the functions of rumen barriers","volume":"10","author":"Shen","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1021\/acs.jafc.8b05480","article-title":"Thymol improves barrier function and attenuates inflammatory responses in porcine intestinal epithelial cells during lipopolysaccharide (LPS)-induced inflammation","volume":"67","author":"Omonijo","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/35067088","article-title":"Multifunctional strands in tight junctions","volume":"2","author":"Tsukita","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8453","DOI":"10.1096\/fj.201802456R","article-title":"Dynamic changes in rumen fermentation and bacterial community following rumen fluid transplantation in a sheep model of rumen acidosis: Implications for rumen health in ruminants","volume":"33","author":"Liu","year":"2019","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"R232","DOI":"10.1152\/ajpregu.00068.2013","article-title":"A high-grain diet causes massive disruption of ruminal epithelial tight junctions in goats","volume":"305","author":"Liu","year":"2013","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zhai, Z., Ni, X., Jin, C., Ren, W., Li, J., Deng, J., Deng, B., and Yin, Y. (2018). Cecropin A modulates tight junction-related protein expression and enhances the barrier function of porcine intestinal epithelial cells by suppressing the MEK\/ERK pathway. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19071941"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.3389\/fimmu.2019.02042","article-title":"Short-chain fatty acids regulate the immune responses via G protein-coupled receptor 41 in bovine rumen epithelial cells","volume":"10","author":"Zhan","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4013575","DOI":"10.1155\/2022\/4013575","article-title":"Protective Mechanism of Leucine and Isoleucine against H2O2-Induced Oxidative Damage in Bovine Mammary Epithelial Cells","volume":"2022","author":"Wu","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.3168\/jds.2017-14328","article-title":"The protective effect of chlorogenic acid on bovine mammary epithelial cells and neutrophil function","volume":"101","author":"Gong","year":"2018","journal-title":"J. Dairy Sci."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/5\/337\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:09:23Z","timestamp":1760137763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/5\/337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,11]]},"references-count":56,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["toxins14050337"],"URL":"https:\/\/doi.org\/10.3390\/toxins14050337","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,11]]}}}