{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:27:27Z","timestamp":1791044847981,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31872539"],"award-info":[{"award-number":["31872539"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Dairy cows receiving a prolonged high-concentrate diet express an elevated concentration of lipopolysaccharides (LPSs) in the peripheral blood circulation, accompanied by a series of systemic inflammatory responses; however, the specific impacts of inflammation are yet to be determined. Cecropin-like antimicrobial peptides have become a research hotspot regarding antimicrobial peptides because of their excellent anti-inflammatory activities, and cecropin A is a major member of the cecropin family. To elucidate the mechanism of cecropin A as anti-inflammatory under the condition of sub-acute ruminal acidosis (SARA) in dairy cows, we induced inflammation in bEECs with LPS (10 \u00b5g\/mL) and then added cecropin A (25 \u00b5M). Afterwards, we detected three categories of indexes including oxidative stress indices, inflammation-related genes, and apoptosis-related genes in bovine endometrial epithelial cells (bEECs). The results indicated that cecropin A has the ability to reduce inflammatory factors TNF-\u03b1, IL-1\u03b2, and IL-8 and inhibit the MAPK pathway to alleviate inflammation. In addition, cecropin A is able to reduce reactive oxygen species (ROS) levels and alleviates LPS-induced oxidative stress and mitochondrial dysfunction by downregulating NADPH Oxidase (NOX), and upregulating catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Furthermore, cecropin A demonstrates the ability to inhibit apoptosis by suppressing the mitochondrial-dependent apoptotic pathway, specifically Fas\/FasL-caspase-8\/-3. The observed increase in the Bcl-2\/Bax ratio, a known apoptosis regulator, further supports this finding. In conclusion, our study presents novel solutions for addressing inflammatory responses associated with SARA.<\/jats:p>","DOI":"10.3390\/ani14050768","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T08:13:44Z","timestamp":1709194424000},"page":"768","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Cecropin A Alleviates LPS-Induced Oxidative Stress and Apoptosis of Bovine Endometrial Epithelial Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2844-993X","authenticated-orcid":false,"given":"Yu","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"},{"name":"Mianyang Habio Bioengineering Co., Ltd., Mianyang 621000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingkun","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiong","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory Institute of Animal Science, Ningxia Academy of Agricultural and Forestry Sciences, Yinchuan 750000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8525-7061","authenticated-orcid":false,"given":"Song","family":"Hua","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1080\/10495398.2020.1806073","article-title":"Long-term high-concentrate diet feeding induces apoptosis of rumen epithelial cells and inflammation of rumen epithelium in dairy cows","volume":"33","author":"Dai","year":"2022","journal-title":"Anim. Biotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5707","DOI":"10.2147\/JIR.S374318","article-title":"LPS-Induced Activation of the cGAS-STING Pathway is Regulated by Mitochondrial Dysfunction and Mitochondrial DNA Leakage in Endometritis","volume":"15","author":"Li","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Banskota, S., Wang, H., Kwon, Y.H., Gautam, J., Haq, S., Grondin, J., Steinberg, G.R., and Khan, W.I. (2023). Inhibition of NADPH Oxidase (NOX) 2 Mitigates Colitis in Mice with Impaired Macrophage AMPK Function. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051443"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.freeradbiomed.2023.01.004","article-title":"Bazedoxifene-induced ROS promote mitochondrial dysfunction and enhance osimertinib sensitivity by inhibiting the p-STAT3\/SOCS3 and KEAP1\/NRF2 pathways in non-small cell lung cancer","volume":"196","author":"Meng","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9056845","DOI":"10.1155\/2019\/9056845","article-title":"Salvianolic Acid C against Acetaminophen-Induced Acute Liver Injury by Attenuating Inflammation, Oxidative Stress, and Apoptosis through Inhibition of the Keap1\/Nrf2\/HO-1 Signaling","volume":"2019","author":"Wu","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lutz, A., Sanwald, J., Thomas, M., Feuer, R., Sawodny, O., Ederer, M., Borner, C., Humar, M., and Merfort, I. (2014). Interleukin-1\u03b2 enhances FasL-induced caspase-3\/-7 activity without increasing apoptosis in primary mouse hepatocytes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115603"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3389\/fphys.2019.00117","article-title":"IL-1\u03b2 and TNF\u03b1 differentially influence NF-\u03baB activity and FasL-induced apoptosis in primary murine hepatocytes during LPS-induced inflammation","volume":"10","author":"Rex","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_8","first-page":"951","article-title":"Caspase 3 expression and plasma level of Fas ligand as apoptosis biomarkers in inflammatory endotoxemic lung injury","volume":"57","author":"Fodor","year":"2016","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16058","DOI":"10.1038\/cddiscovery.2016.58","article-title":"Precambrian origins of the TNFR superfamily","volume":"2","author":"Quistad","year":"2016","journal-title":"Cell Death Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.4103\/1673-5374.135315","article-title":"Heavy ion and X-ray irradiation alter the cytoskeleton and cytomechanics of cortical neurons","volume":"9","author":"Du","year":"2014","journal-title":"Neural Regen. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S0968-0004(01)01844-8","article-title":"The mitochondrial apoptosome: A killer unleashed by the cytochrome seas","volume":"26","author":"Adrain","year":"2001","journal-title":"Trends Biochem. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.1093\/emboj\/cdg423","article-title":"Mitochondrial release of AIF and EndoG requires caspase activation downstream of Bax\/Bak-mediated permeabilization","volume":"22","author":"Arnoult","year":"2003","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39018","DOI":"10.1074\/jbc.M006495200","article-title":"The Fas-induced apoptosis analyzed by high throughput proteome analysis","volume":"275","author":"Gerner","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16391","DOI":"10.1074\/jbc.M010498200","article-title":"NADH Oxidase Activity of Mitochondrial Apoptosis-inducing Factor","volume":"276","author":"Miramar","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_15","first-page":"6635","article-title":"Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292: 246\u2013248. 1981","volume":"182","author":"Steiner","year":"2009","journal-title":"J. Immunol. (Baltimore Md. 1950)"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41296","DOI":"10.1074\/jbc.M111.269225","article-title":"Structure and function of papiliocin with antimicrobial and anti-inflammatory activities isolated from the swallowtail butterfly, Papilio xuthus","volume":"286","author":"Kim","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.4049\/jimmunol.167.6.3329","article-title":"Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-\u03b1 by blocking the binding of LPS to CD14+ cells","volume":"167","author":"Nagaoka","year":"2001","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/arch.21193","article-title":"Anti-inflammatory activities of cecropin a and its mechanism of action","volume":"88","author":"Lee","year":"2015","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"748447","DOI":"10.3389\/fimmu.2021.748447","article-title":"Interaction between chronic endometritis caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","unstructured":"Meng, M., Zhao, X., Huo, R., Li, X., Chang, G., and Shen, X. (2023). Disodium Fumarate Alleviates Endoplasmic Reticulum Stress, Mitochondrial Damage, and Oxidative Stress Induced by the High-Concentrate Diet in the Mammary Gland Tissue of Hu Sheep. Antioxidants, 12.","DOI":"10.3390\/antiox12020223"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.theriogenology.2023.05.013","article-title":"Proteomic analysis of uterine lavage fluid of dairy cows at different time after delivery by mass spectrometry","volume":"207","author":"Jiang","year":"2023","journal-title":"Theriogenology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mallona, I., Weiss, J., and Egea-Cortines, M. (2011). PcrEfficiency: A Web tool for PCR amplification efficiency prediction. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-404"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.theriogenology.2019.12.008","article-title":"The attenuation of the toxic effects of LPS on mouse pre-implantation development by alpha-lipoic acid","volume":"143","author":"Mokhtari","year":"2020","journal-title":"Theriogenology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zeng, J., Lv, J., Duan, H., Yang, S., Wu, J., Yan, Z., Zhang, R., Hu, J., and Zhang, Y. (2023). Subacute Ruminal Acidosis as a Potential Factor that Induces Endometrium Injury in Sheep. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021192"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Li, X., Zuo, S., Wang, B., Zhang, K., and Wang, Y. (2022). Antimicrobial mechanisms and clinical application prospects of antimicrobial peptides. Molecules, 27.","DOI":"10.3390\/molecules27092675"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Luo, Y., and Song, Y. (2021). Mechanism of antimicrobial peptides: Antimicrobial, anti-inflammatory and antibiofilm activities. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111401"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6211","DOI":"10.1074\/jbc.M110.181206","article-title":"Antimicrobial peptides increase tolerance to oxidant stress in Drosophila melanogaster","volume":"286","author":"Zhao","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1747-0285.2007.00540.x","article-title":"The Antimicrobial Peptide PR-39 has a Protective Effect Against HeLa Cell Apoptosis","volume":"70","author":"Ross","year":"2007","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1038\/jid.2011.112","article-title":"Antimicrobial and anti-inflammatory effects of cecropin A (1\u20138)\u2013Magainin2 (1\u201312) hybrid peptide analog P5 against Malassezia furfur infection in human keratinocytes","volume":"131","author":"Ryu","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Georgiou, C.D., and Margaritis, L.H. (2021). Oxidative stress and NADPH oxidase: Connecting electromagnetic fields, cation channels and biological effects. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810041"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sul, O.-J., and Ra, S.W. (2021). Quercetin prevents LPS-induced oxidative stress and inflammation by modulating NOX2\/ROS\/NF-kB in lung epithelial cells. Molecules, 26.","DOI":"10.3390\/molecules26226949"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ali, S.S., Ahsan, H., Zia, M.K., Siddiqui, T., and Khan, F.H. (2020). Understanding oxidants and antioxidants: Classical team with new players. J. Food Biochem., 44.","DOI":"10.1111\/jfbc.13145"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.freeradbiomed.2018.11.034","article-title":"LPS protects macrophages from AIF-independent parthanatos by downregulation of PARP1 expression, induction of SOD2 expression, and a metabolic shift to aerobic glycolysis","volume":"131","author":"Regdon","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-015-0332-6","article-title":"Systemic inflammation and microglial activation: Systematic review of animal experiments","volume":"12","author":"Hoogland","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109199","DOI":"10.1016\/j.intimp.2022.109199","article-title":"CircPalm2 knockdown alleviates LPS-evoked pulmonary microvascular endothelial cell apoptosis and inflammation via miR-450b-5p\/ROCK1 axis","volume":"113","author":"Mu","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/iep.12459","article-title":"KLF13 overexpression protects sepsis-induced myocardial injury and LPS-induced inflammation and apoptosis","volume":"104","author":"Zeng","year":"2023","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Song, P., Liu, C., Sun, M., Liu, J., Lin, P., Wang, A., and Jin, Y. (2022). Oxidative stress induces bovine endometrial epithelial cell damage through mitochondria-dependent pathways. Animals, 12.","DOI":"10.3390\/ani12182444"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.3389\/fimmu.2018.02363","article-title":"Potential role of cytochrome c and tryptase in psoriasis and psoriatic arthritis pathogenesis: Focus on resistance to apoptosis and oxidative stress","volume":"9","author":"Chimenti","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.biocel.2014.06.015","article-title":"LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection","volume":"54","author":"Sun","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"925824","DOI":"10.1155\/2012\/925824","article-title":"Phyllanthus urinaria induces apoptosis in human osteosarcoma 143B cells via activation of Fas\/FasL-and mitochondria-mediated pathways","volume":"2012","author":"Wu","year":"2012","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"C1235","DOI":"10.1152\/ajpcell.00228.2003","article-title":"PKC\u03f5 is involved in JNK activation that mediates LPS-induced TNF-\u03b1, which induces apoptosis in macrophages","volume":"285","author":"Comalada","year":"2003","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.4049\/jimmunol.171.4.1868","article-title":"Pathogen-associated molecular patterns sensitize macrophages to Fas ligand-induced apoptosis and IL-1\u03b2 release","volume":"171","author":"Fukui","year":"2003","journal-title":"J. Immunol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/14\/5\/768\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:07:15Z","timestamp":1760105235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/14\/5\/768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,29]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ani14050768"],"URL":"https:\/\/doi.org\/10.3390\/ani14050768","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,29]]}}}