{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:02:09Z","timestamp":1789794129979,"version":"4.0.1"},"reference-count":59,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32460851"],"award-info":[{"award-number":["32460851"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32460851"],"award-info":[{"award-number":["32460851"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Postdoctoral Fund of the Gansu Provincial Department of Human Resources and Social Security","award":["03824006"],"award-info":[{"award-number":["03824006"]}]},{"name":"Nanchang Normal University Science and Technology Innovation Team","award":["NCNUCXTD001"],"award-info":[{"award-number":["NCNUCXTD001"]}],"id":[{"id":"https:\/\/ror.org\/01sbpdt14","id-type":"ROR","asserted-by":"crossref"}]},{"award":["NCNUCXTD001"],"award-info":[{"award-number":["NCNUCXTD001"]}],"id":[{"id":"https:\/\/ror.org\/01sbpdt14","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Mastitis severely hinders dairy farming, with Streptococcus agalactiae (S. agalactiae) serving as a major causative pathogen. Prolonged antibiotic administration promotes the emergence of multidrug-resistant strains, thereby compromising mastitis control. Consequently, novel natural antibacterial agents are urgently needed. In this study, bacteriostatic assays identified the MIC of rosmarinic acid (RA) against S. agalactiae as 8 mg\/mL. At the MIC, RA reduced the adhesion capacity of S. agalactiae by 16.6% and inhibited biofilm formation by 25.09%. RA also disrupted bacterial membrane architecture and markedly downregulated the expression of virulence factors. A mouse model of mastitis treated with varying doses of RA (25, 50, and 100 mg\/kg) indicated that RA attenuated pathological damage to the mammary duct architecture and ameliorated inflammatory responses in S. agalactiae-infected mice. ELISA revealed that RA significantly reduced pro-inflammatory mediators, including IL-1\u03b1, IL-1\u03b2, IL-6, and TNF-\u03b1. RT-qPCR results indicated that mRNA expression levels of TLR2, NF-\u03baB, AKT, and PI3K were substantially reduced following RA treatment, whereas apoptosis-related genes p53, RUNX1, and Bim exhibited distinct expression patterns. Western blotting analysis further indicated that RA modulated the phosphorylation of Bim, RUNX1, and p53 in mastitis tissues, suppressed the TLR2\/NF-\u03baB inflammatory signaling pathway, and regulated the PI3K\/AKT cascade. By targeting multiple pathways, RA suppressed S. agalactiae proliferation and attenuated mammary gland inflammation, highlighting its potential as a green therapeutic agent for sustainable animal husbandry.<\/jats:p>","DOI":"10.3390\/ani16182917","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:50:27Z","timestamp":1789566627000},"page":"2917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibacterial Activity of Rosmarinic Acid Against Streptococcus agalactiae and Its Anti-Inflammatory Effects in Mouse Mastitis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0835-1177","authenticated-orcid":false,"given":"Jishang","family":"Gong","sequence":"first","affiliation":[{"name":"Institute of Biological Technology, Nanchang Normal University, Nanchang 330032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewen","family":"Chai","sequence":"additional","affiliation":[{"name":"Institute of Biological Technology, Nanchang Normal University, Nanchang 330032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbei","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biological Technology, Nanchang Normal University, Nanchang 330032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Biological Technology, Nanchang Normal University, Nanchang 330032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biological Technology, Nanchang Normal University, Nanchang 330032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiguo","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biological Technology, Nanchang Normal University, Nanchang 330032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institute of Biological Technology, Nanchang Normal University, Nanchang 330032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6712-3473","authenticated-orcid":false,"given":"Yuanfei","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Biological Technology, Nanchang Normal University, Nanchang 330032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6483","DOI":"10.3168\/jds.2012-5594","article-title":"Examining the effect of intramammary infections with minor mastitis pathogens on the acquisition of new intramammary infections with major mastitis pathogens\u2014A systematic review and meta-analysis","volume":"95","author":"Reyher","year":"2012","journal-title":"J. Dairy Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.3168\/jds.2013-7266","article-title":"Pathogen-specific effects on milk yield in repeated clinical mastitis episodes in Holstein dairy cows","volume":"97","author":"Hertl","year":"2014","journal-title":"J. Dairy Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Antanaitis, R., Juozaitien\u0117, V., Jonike, V., Baumgartner, W., and Paulauskas, A. (2022). Subclinical Mastitis Detected during the Last Gestation Period Can Increase the Risk of Stillbirth in Dairy Calves. Animals, 12.","DOI":"10.3390\/ani12111394"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4978","DOI":"10.3168\/jds.2022-22803","article-title":"Early detection of subclinical mastitis in lactating dairy cows using cow-level features","volume":"106","author":"Pakrashi","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/01652176.2021.1882713","article-title":"Advances in therapeutic and managemental approaches of bovine mastitis: A comprehensive review","volume":"41","author":"Sharun","year":"2021","journal-title":"Vet. Q."},{"key":"ref_6","first-page":"429","article-title":"Streptococcus agalactiae mastitis: A review","volume":"38","author":"Keefe","year":"1997","journal-title":"Can. Vet. J. LA Rev. Vet. Can."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rosini, R., and Margarit, I. (2015). Biofilm formation by Streptococcus agalactiae: Influence of environmental conditions and implicated virulence factors. Front. Cell. Infect. Microbiol., 5.","DOI":"10.3389\/fcimb.2015.00006"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21003","DOI":"10.1074\/jbc.M114.553073","article-title":"FbsC, a novel fibrinogen-binding protein, promotes Streptococcus agalactiae-host cell interactions","volume":"289","author":"Buscetta","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1128\/CMR.18.1.102-127.2005","article-title":"Surface proteins of Streptococcus agalactiae and related proteins in other bacterial pathogens","volume":"18","author":"Lindahl","year":"2005","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pietrocola, G., Arciola, C.R., Rindi, S., Montanaro, L., and Speziale, P. (2018). Streptococcus agalactiae Non-Pilus, Cell Wall-Anchored Proteins: Involvement in Colonization and Pathogenesis and Potential as Vaccine Candidates. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00602"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liu, Y., and Liu, J. (2022). Group B Streptococcus: Virulence Factors and Pathogenic Mechanism. Microorganisms, 10.","DOI":"10.3390\/microorganisms10122483"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.GPP3-0007-2018","article-title":"Group B Streptococcus (Streptococcus agalactiae)","volume":"7","author":"Raabe","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gong, J., Li, T., Li, Y., Xiong, X., Xu, J., Chai, X., and Ma, Y. (2024). UID-Dual Transcriptome Sequencing Analysis of the Molecular Interactions between Streptococcus agalactiae ATCC 27956 and Mammary Epithelial Cells. Animals, 14.","DOI":"10.3390\/ani14172587"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Huang, L., Ahmed, S., Gu, Y., Huang, J., An, B., Wu, C., Zhou, Y., and Cheng, G. (2021). The Effects of Natural Products and Environmental Conditions on Antimicrobial Resistance. Molecules, 26.","DOI":"10.3390\/molecules26144277"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s12272-022-01378-2","article-title":"Biomedical features and therapeutic potential of rosmarinic acid","volume":"45","author":"Noor","year":"2022","journal-title":"Arch. Pharmacal Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kernou, O.N., Azzouz, Z., Madani, K., and Rijo, P. (2023). Application of Rosmarinic Acid with Its Derivatives in the Treatment of Microbial Pathogens. Molecules, 28.","DOI":"10.3390\/molecules28104243"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5190808","DOI":"10.1155\/2021\/5190808","article-title":"Network Pharmacology and Molecular Docking Suggest the Mechanism for Biological Activity of Rosmarinic Acid","volume":"2021","author":"Guan","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med. eCAM"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1002\/bab.2248","article-title":"The antibacterial mechanism of perilla rosmarinic acid","volume":"69","author":"Zhang","year":"2022","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107318","DOI":"10.1016\/j.bioorg.2024.107318","article-title":"Discovery of a novel class of rosmarinic acid derivatives as antibacterial agents: Synthesis, structure-activity relationship and mechanism of action","volume":"146","author":"Wang","year":"2024","journal-title":"Bioorg. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ijfoodmicro.2016.08.042","article-title":"Effect of sodium alginate coating incorporated with nisin, Cinnamomum zeylanicum, and rosemary essential oils on microbial quality of chicken meat and fate of Listeria monocytogenes during refrigeration","volume":"238","author":"Raeisi","year":"2016","journal-title":"Int. J. Food Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tsukamoto, Y., Ikeda, S., Uwai, K., Taguchi, R., Chayama, K., Sakaguchi, T., Narita, R., Yao, W.L., Takeuchi, F., and Otakaki, Y. (2018). Rosmarinic acid is a novel inhibitor for Hepatitis B virus replication targeting viral epsilon RNA-polymerase interaction. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197664"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10753-017-0700-8","article-title":"Anti-inflammatory Effects of Rosmarinic Acid in Lipopolysaccharide-Induced Mastitis in Mice","volume":"41","author":"Jiang","year":"2018","journal-title":"Inflammation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"358","DOI":"10.5455\/jice.20160906035020","article-title":"Antibacterial synergy between rosmarinic acid and antibiotics against methicillin-resistant Staphylococcus aureus","volume":"5","author":"Ekambaram","year":"2016","journal-title":"J. Intercult. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4939-6817-6_10","article-title":"Inhibition of Bacterial Growth by Peptide-Conjugated Morpholino Oligomers","volume":"1565","author":"Daly","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chen, S., Zhang, H., Zhai, J., Wang, H., Chen, X., and Qi, Y. (2023). Prevalence of clinical mastitis and its associated risk factors among dairy cattle in mainland China during 1982\u20132022: A systematic review and meta-analysis. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1185995"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.5713\/ab.24.0590","article-title":"Nanoparticles as an alternative treatment for bovine mastitis: State-of-the-art review","volume":"38","year":"2025","journal-title":"Anim. Biosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4797","DOI":"10.3168\/jds.2016-12334","article-title":"Incidence of clinical mastitis and distribution of pathogens on large Chinese dairy farms","volume":"100","author":"Gao","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_28","first-page":"153626","article-title":"Antibacterial plant compounds, extracts and essential oils: An updated review on their effects and putative mechanisms of action","volume":"90","author":"Micol","year":"2021","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.4062\/biomolther.2016.035","article-title":"Rosmarinic acid potentiates pentobarbital-induced sleep behaviors and non-rapid eye movement (NREM) sleep through the activation of GABA(A)-ergic systems","volume":"25","author":"Kwon","year":"2017","journal-title":"Biomol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jphs.2016.09.003","article-title":"Rosmarinic acid inhibits inflammation and angiogenesis of hepatocellular carcinoma by suppression of NF-\u03baB signaling in H22 tumor-bearing mice","volume":"132","author":"Cao","year":"2016","journal-title":"J. Pharmacol. Sci."},{"key":"ref_31","first-page":"1292","article-title":"Studies on antibacterial constituents of Perilla frutescens","volume":"27","year":"2006","journal-title":"Chem. J. Chin. Univ.-Chin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1128\/AAC.00041-07","article-title":"Antiviral and anti-inflammatory effects of rosmarinic acid in an experimental murine model of Japanese encephalitis","volume":"51","author":"Swarup","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shing, S.R., Ramos, A.R., Patras, K.A., Riestra, A.M., McCabe, S., Nizet, V., and Coady, A. (2019). The Fungal Pathogen Candida albicans Promotes Bladder Colonization of Group B Streptococcus. Front. Cell. Infect. Microbiol., 9.","DOI":"10.3389\/fcimb.2019.00437"},{"key":"ref_34","first-page":"1747","article-title":"Rosmarinic acid interaction with planktonic and biofilm Staphylococcus aureus","volume":"8","author":"Grancai","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.rvsc.2020.05.016","article-title":"Relative expression of genes associated with adhesion to bovine mammary epithelial cells by Streptococcus uberis","volume":"132","author":"Fessia","year":"2020","journal-title":"Res. Vet. Sci."},{"key":"ref_36","first-page":"2954","article-title":"Advances on virulence factors of Streptococcus agalactiae of dairy cows mastitis","volume":"51","author":"Wu","year":"2020","journal-title":"Acta Vet. Zootech. Sin."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/infdis\/jiy341","article-title":"Group B Streptococcus Biofilm Regulatory Protein A Contributes to Bacterial Physiology and Innate Immune Resistance","volume":"218","author":"Patras","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7465","DOI":"10.1073\/pnas.1815572116","article-title":"Dual actions of group B Streptococcus capsular sialic acid provide resistance to platelet-mediated antimicrobial killing","volume":"116","author":"Uchiyama","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Shang, F., Wang, H., and Xue, T. (2020). Anti-Biofilm Effect of Tea Saponin on a Streptococcus agalactiae Strain Isolated from Bovine Mastitis. Animals, 10.","DOI":"10.3390\/ani10091713"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/vms3.509","article-title":"Infective mastitis due to bovine-associated Streptococcus dysgalactiae contributes to clinical persistent presentation in a murine mastitis model","volume":"7","author":"An","year":"2021","journal-title":"Vet. Med. Sci."},{"key":"ref_41","first-page":"117","article-title":"Isolation of Streptococcus agalactiae from dairy cattle and construction of its induced mastitis mouse model","volume":"53","author":"Liu","year":"2021","journal-title":"Anim. Husb. Vet. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Garlanda, C., and Mantovani, A. (2013). Ligands and receptors of the interleukin-1 family in immunity and disease. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00396"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/infdis\/149.3.339","article-title":"Fever: The old and the new","volume":"149","author":"Atkins","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Fukuyama, K., Islam, M.A., Takagi, M., Ikeda-Ohtsubo, W., Kurata, S., Aso, H., Vignolo, G., Villena, J., and Kitazawa, H. (2020). Evaluation of the Immunomodulatory Ability of Lactic Acid Bacteria Isolated from Feedlot Cattle Against Mastitis Using a Bovine Mammary Epithelial Cells In Vitro Assay. Pathogens, 9, Erratum in Pathogens\u00a02020, 9, 574. https:\/\/doi.org\/10.3390\/pathogens9070574.","DOI":"10.3390\/pathogens9070574"},{"key":"ref_46","first-page":"659801","article-title":"The Immunology of Mammary Gland of Dairy Ruminants between Healthy and Inflammatory Conditions","volume":"2014","year":"2014","journal-title":"J. Vet. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","article-title":"Regulation and functions of the IL-10 family of cytokines in inflammation and disease","volume":"29","author":"Ouyang","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"106675","DOI":"10.1016\/j.micpath.2024.106675","article-title":"Comparative analysis of Streptococcus agalactiae serotypes Ia and II isolates from China and Pakistan in a murine model: A focus on pathogenesis and immune response","volume":"191","author":"Leghari","year":"2024","journal-title":"Microb. Pathog."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"202","DOI":"10.32725\/jab.2021.024","article-title":"Rosmarinic acid suppresses inflammation, angiogenesis, and improves paclitaxel induced apoptosis in a breast cancer model via NF3 \u03baB-p53-caspase-3 pathways modulation","volume":"19","author":"Mahmoud","year":"2021","journal-title":"J. Appl. Biomed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.vetmic.2019.02.016","article-title":"Adherent\/invasive capacities of bovine-associated Aerococcus viridans contribute to pathogenesis of acute mastitis in a murine model","volume":"230","author":"Liu","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_51","first-page":"463","article-title":"Escherichia coli and Staphylococcus aureus elicit differential innate immune responses following intramammary infection","volume":"11","author":"Bannerman","year":"2004","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0204923","DOI":"10.1128\/mbio.02049-23","article-title":"GBS hyaluronidase mediates immune suppression in a TLR2\/4- and IL-10-dependent manner during pregnancy-associated infection","volume":"14","author":"Coleman","year":"2023","journal-title":"mBio"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"109206","DOI":"10.1016\/j.intimp.2022.109206","article-title":"Matrine attenuates bovine mammary epithelial cells inflammatory responses induced by Streptococcus agalactiae through inhibiting NF-\u03baB and MAPK signaling pathways","volume":"112","author":"Li","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6401","DOI":"10.2147\/IJN.S101285","article-title":"Upregulation of Akt\/NF-\u03baB-regulated inflammation and Akt\/Bad-related apoptosis signaling pathway involved in hepatic carcinoma process: Suppression by carnosic acid nanoparticle","volume":"11","author":"Tang","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1002\/ijc.24748","article-title":"Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt","volume":"125","author":"Bai","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e6145","DOI":"10.1590\/1414-431x20176145","article-title":"Effect of a rosmarinic acid supplemented hemodialysis fluid on inflammation of human vascular endothelial cells","volume":"50","author":"Wang","year":"2017","journal-title":"Braz. J. Med. Biol. Res. Rev. Bras. Pesqui. Medicas Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"63","DOI":"10.12659\/MSMBR.913331","article-title":"Rosmarinic Acid Analogue-11 Induces Apoptosis of Human Gastric Cancer SGC-7901 Cells via the Epidermal Growth Factor Receptor (EGFR)\/Akt\/Nuclear Factor kappa B (NF-\u03baB) Pathway","volume":"25","author":"Li","year":"2019","journal-title":"Med. Sci. Monit. Basic Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/cdd.2015.61","article-title":"The BH3-only protein BIM contributes to late-stage involution in the mouse mammary gland","volume":"23","author":"Schuler","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/sj.onc.1206261","article-title":"Activation of ERK1\/2 by deltaRaf-1:ER* represses Bim expression independently of the JNK or PI3K pathways","volume":"22","author":"Weston","year":"2003","journal-title":"Oncogene"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/18\/2917\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:19:39Z","timestamp":1789791579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/18\/2917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":59,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ani16182917"],"URL":"https:\/\/doi.org\/10.3390\/ani16182917","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}