Role of TLR/NF-κB/MAPK signaling pathways in mastitis pathogenesis and their potential as therapeutic targets – a review
References
- Ali I., Li C., Kuang M., Shah A.U., Shafiq M., Ahmad M.A., Abdalmegeed D., Li L., Wang G. (2022). Nrf2 activation and NF-Kb & caspase/bax signaling inhibition by sodium butyrate alleviates LPS-induced cell injury in bovine mammary epithelial cells. Mol. Immunol., 148: 54–67.
- Arbab S., Ullah H., Bano I., Li K., Hassan I., Wang W., Qadeer A., Zhang J. (2022). Evaluation of in vitro antibacterial effect of essential oil and some herbal plant extract used against mastitis pathogens. Vet. Med. Sci., 8: 2655–2661.
- Arikan M.S., Mat B., Alkan H., Çevrimli M.B., Akin A.C., Başar E.K., Tekindal M.A. (2024). Determination of subclinical mastitis prevalence in dairy cows in Türkiye through meta-analysis and production loss calculation. Pak. Vet. J., 44: 391–399
- Arsaute S., Reinoso E.B., Cecchini M.E., Moliva M.V., Montironi I.D., Cariddi L.N., (2024). Minthostachys verticillata essential oil modulates cytokine synthesis and Staphylococcus aureus internalization in MAC-T cells at least through TLR4/MyD88/NFkB pathway. Vet. Res. Commun., 48: 3727–3742
- Ayemele A.G., Tilahun M., Lingling S., Elsaadawy S.A., Guo Z., Zhao G., Xu J., Bu D. (2021). Oxidative stress in dairy cows: Insights into the mechanistic mode of actions and mitigating strategies. Antioxidants, 10: 1918
- Bai X., Wang X., Lin T., Dong W., Gao Y., Ji P., Zhang Y., Zhao X., Zhang Q. (2022). Toll-like receptor 2 is associated with the immune response, apoptosis, and angiogenesis in the mammary glands of dairy cows with clinical mastitis. Int. J. Mol. Sci., 23: 10717.
- Bao L., Sun H., Zhao Y., Feng L., Wu K., Shang S., Xu J., Shan R., Duan S., Qiu M., Zhang N. (2023). Hexadecanamide alleviates Staphylococcus aureus-induced mastitis in mice by inhibiting inflammatory responses and restoring blood-milk barrier integrity. PLoS Pathog., 19: e1011764
- Bhat R.R., Bhat N.N., Shabir A., Mir M.U., Ahmad S.B., Hussain I., Hussain S.A., Ali A., Shamim K., Rehman M.U. (2024). SNP analysis of TLR4 promoter and its transcriptional factor binding profile in relevance to bovine subclinical mastitis. Biochem. Genet., 62: 3605–3623
- Bhattarai D., Worku T., Dad R., Rehman Z.U., Gong X., Zhang S. (2018). Mechanism of pattern recognition receptors (PRRs) and host pathogen interplay in bovine mastitis. Microb. Pathog., 120: 64–70.
- Biswas S., Mukherjee R., Chakravarti S., Bera A.K., Bandyopadhyay S., De U.K., Datta S. (2023). Influence of pathogens specific sub-clinical mastitis on oxidative status and mineral metabolism of yak. Emerg. Anim. Species, 8: 100028.
- Cai M., Fan W., Li X., Sun H., Dai L., Lei D., Dai Y., Liao Y. (2021). The regulation of Staphylococcus aureus-induced inflammatory responses in bovine mammary epithelial cells. Front. Vet. Sci., 8: 683886.
- Cai X., Zhou Z., Kan X., Xu P., Guo W., Fu S., Liu J., Jia Y. (2024). Daidzein relieves lipopolysaccharide-induced mastitis through inhibiting MAPKs and AKT/NF-κB P65 signaling pathways. Rev. Bras. Farmacogn., 34: 853–864..
- Cao G., Liu J., Liu H., Chen X., Yu N., Li X., Xu F. (2023). Integration of network pharmacology and molecular docking to analyse the mechanism of action of oregano essential oil in the treatment of bovine mastitis. Vet. Sci., 10: 350.
- Che H.Y., Zhou C.H., Lyu C.C., Meng Y., He Y.T., Wang H.Q., Wu H.Y., Zhang J.B., Yuan B. (2023). Allicin alleviated LPS-induced mastitis via the TLR4/NF-κB signaling pathway in bovine mammary epithelial cells. Int. J. Mol. Sci., 24: 3805.
- Chen H., Liu C., Xiang M., Yu J., Xia Y., Hu X., Wang D., Tao B., Zhang Y., Cheng L. (2022). Contribution of the mutation rs8193069 in TLR4 to mastitis resistance and performance in Holstein cows in southern China. Vet. Med. Sci., 8: 357–366.
- Chen Y., Yang J., Huang Z., Yin B., Umar T., Yang C., Zhang X., Jing H., Guo S., Guo M., Deng G. (2022). Vitexin mitigates Staphylococcus aureus-induced mastitis via regulation of ROS/ER stress/NF-κB/MAPK pathway. Oxid. Med. Cell. Longev., 2022: 7977433.
- Cobirka M., Tancin V., Slama P. (2020). Epidemiology and classification of mastitis. Animals, 10: 2212.
- Corrêa D.C., Nunes G.T., Barcelos R.A.D., Dos Santos J.R., Vogel F.S.F., Cargnelutti J.F. (2024). Economic losses caused by mastitis and the influence of climate variation on the occurrence of the disease in a dairy cattle farm in southern Brazil. Trop. Anim. Health Prod., 56: 1–9.
- De Vliegher S., Ohnstad I., Piepers S. (2018). Management and prevention of mastitis: A multifactorial approach with a focus on milking, bedding and data-management. J. Integr. Agric., 17: 1214–1233.
- Duan T., Du Y., Xing C., Wang, H.Y., Wang R.F. (2022). Toll-like receptor signaling and its role in cell-mediated immunity. Front. Immunol., 13: 812774.
- Edres H.A., Elmassry I.H., Lebda M.A., Othman S.I., El-Karim D.R., Rudayni H.A., Ebied S.K., Allam A.A., Hashem A.E. (2025). Berberine and Cyperus rotundus extract nanoformulations protect the rats against Staphylococcus-induced mastitis via antioxidant and anti-inflammatory activities: Role of MAPK signaling. Cell Biochem. Biophys., 83: 2167–2183.
- Fan X., Qadeer A., Asiri M., Alzahrani F.M., Alzahrani K., Alsharif K.F., Jiang X. (2025). Traditional Chinese medicine and plant-derived bioactive compounds as sustainable alternatives to antibiotics in bovine mastitis: a review. Front. Vet. Sci., 12: 1642647.
- Feng F., Li Y., Wang J., Dong Y., Li Y., Luoreng Z., Wang X. (2024). LncRNA CA12-AS1 targets miR-133a to promote LPS-induced inflammatory response in bovine mammary epithelial cells. Int. J. Biol. Macromol., 261: 129710.
- Gao Y., Li C., Zhang X., Yao D., Zhang Y. (2025). MiR-214 inhibits NF-κB pathway activation to alleviate lipopolysaccharide-induced mastitis by targeting TRAF1. Theriogenology, 237: 76–84.
- Ge B.J., Zhao P., Li H.T., Sang R., Wang M., Zhou H.Y, Zhang X.M. (2021). Taraxacum mongolicum protects against Staphylococcus aureus-infected mastitis by exerting anti-inflammatory role via TLR2-NF-κB/MAPKs pathways in mice. J. Ethnopharmacol., 268: 113595.
- Guo Y., Zhang J., Yuan T., Yang C., Zhou Q., Shaukat A., Deng G., Wang X. (2025). Luteolin alleviates inflammation induced by staphylococcus aureus in bovine mammary epithelial cells by attenuating NF-κB and MAPK activation. Vet. Sci., 12: 96.
- He X., Wang J., Sun L., Ma W., Li M., Yu S., Zhou Q., Jiang J. (2023). Wogonin attenuates inflammation and oxidative stress in lipopolysaccharide-induced mastitis by inhibiting Akt/NF-κB pathway and activating the Nrf2/HO-1 signaling. Cell Stress Chaperones, 28: 989–999.
- He Z., Su S., Zhang B., Chen D., Yuan S., Guan W., Zhang S. (2025). Selenium yeast attenuated lipopolysaccharide-induced inflammation in porcine mammary epithelial cells by modulating MAPK and NF-κB signaling pathways. Antioxidants, 14: 334.
- Hogeveen H., Steeneveld W., Wolf C.A. (2019). Production diseases reduce the efficiency of dairy production: A review of the results, methods, and approaches regarding the economics of mastitis. Annu. Rev. Resour. Econ., 11: 289–312.
- Hu X., Tang R., Zhao C., Mu R., Wang Y., Cao Y., Zhang N., Fu Y. (2023). The prevention effect of Bacillus subtilis on Escherichia coli-induced mastitis in mice by suppressing the NF-κB and MAPK signaling pathways. Probiotics Antimicrob. Proteins, 1: 1–8.
- Hu Y., Xie Y., Sun Y., Luo L., Wang H., Zhang R., Ge M. (2025). Anti-inflammatory effects of apigenin on LPS-induced mastitis in lactating SD rats through inhibiting TLR4/NF-κB signaling pathway. Cytokine, 191: 156944.
- Huang Q., Liu J., Peng C., Han X., Tan Z. (2024). Hesperidin ameliorates H2O2-induced bovine mammary epithelial cell oxidative stress via the Nrf2 signaling pathway. J. Anim. Sci. Biotechnol., 15: 57.
- Jiang A., Zhang Y., Zhang X., Wu D., Liu Z., Li S., Liu X., Han Z., Wang C., Wang J., Wei Z. (2020). Morin alleviates LPS-induced mastitis by inhibiting the PI3K/AKT, MAPK, NF-κB and NLRP3 signaling pathway and protecting the integrity of blood-milk barrier. Int. Immunopharmacol., 78: 105972.
- Jiang M., Lv Z., Huang Y., Cheng Z., Meng Z., Yang T., Yan Q., Lin M., Zhan K., Zhao G. (2022). Quercetin alleviates lipopolysaccharide-induced inflammatory response in bovine mammary epithelial cells by suppressing TLR4/NF-κB signaling pathway. Front. Vet. Sci., 9: 915726.
- Kan X., Liu J., Chen Y., Guo W., Xu D., Cheng J., Cao Y., Yang Z., Fu S. (2021). Protective effect of myricetin on LPS-induced mastitis in mice through ERK1/2 and p38 protein author. Naunyn-Schmiedeberg’s Arch. Pharmacol., 394: 1727–1735.
- Khan M.Z., Khan A., Xiao J., Ma J., Ma Y., Chen T., Shao D., Cao Z. (2020 a). Overview of research development on the role of NF-κB signaling in mastitis. Animals, 10: 1625.
- Khan M.Z., Khan A., Xiao J., Ma Y., Ma J., Gao J., Cao Z. (2020 b). Role of the JAK-STAT pathway in bovine mastitis and milk production. Animals, 10: 2107.
- Khan M.Z., Dari G., Khan A., Yu Y. (2022 a). Genetic polymorphisms of TRAPPC9 and CD4 genes and their association with milk production and mastitis resistance phenotypic traits in Chinese Holstein. Front. Vet. Sci., 9: 1008497.
- Khan M.Z., Belhan S., Cetin N., Ayan A., Khan A., Ahmad I., Ma Y., Xiao J., Khan J.M., Shah M.K., Ullah S., Cao Z. (2022 b). Mining for the association of bovine mastitis linked genes to pathological signatures and pathways. Ann. Anim. Sci., 22: 583–591.
https://doi.org/10.2478/aoas-2021-0049 - Khan M.Z., Ma Y., Xiao J., Chen T., Ma J., Liu S., Wang Y., Khan A., Alugongo G.M., Cao Z. (2022 c). Role of selenium and vitamins E and B9 in the alleviation of bovine mastitis during the periparturient period. Antioxidants, 11: 657.
- Khan M.Z., Wang J., Ma Y., Chen T., Ma M., Ullah Q., Khan I.M., Khan A., Cao Z., Liu S. (2023). Genetic polymorphisms in immune- and inflammation-associated genes and their association with bovine mastitis resistance/susceptibility. Front. Immunol., 14: 1082144.
- Khan M.Z., Huang B., Kou X., Chen Y., Liang H., Ullah Q., Khan I.M., Khan A., Chai W., Wang C. (2024 a). Enhancing bovine immune, antioxidant and anti-inflammatory responses with vitamins, rumen-protected amino acids, and trace minerals to prevent periparturient mastitis. Front. Immunol., 14: 1290044.
- Khan M.Z., Li L., Wang T., Liu X., Chen W., Ma Q., Zahoor M., Wang C. (2024 b). Bioactive compounds and probiotics mitigate mastitis by targeting NF-κB signaling pathway. Biomolecules, 14: 1011.
- Khan M.Z., Li L., Zhan Y., Binjiang H., Liu X., Kou X., Khan A., Qadeer A., Ullah Q., Alzahrani K.J., Wang T. (2025). Targeting Nrf2/KEAP1 signaling pathway using bioactive compounds to combat mastitis. Front. Immunol., 16: 1425901.
- Kour S., Sharma N., N B., Kumar P., Soodan J.S., Santos M.V., Son Y.O. (2023). Advances in diagnostic approaches and therapeutic management in bovine mastitis. Vet. Sci., 10: 449.
- Kwok C.T., Chow F.W., Cheung K.Y., Zhang X.Y., Mok D.K., Kwan Y.W., Chan G.H., Leung G.P., Cheung K.W., Lee S.M., Wang N. (2024). Medulla Tetrapanacis water extract alleviates inflammation and infection by regulating macrophage polarization through MAPK signaling pathway. Inflammopharmacology, 32: 393–404.
- Lebda M.A., Elmassry I.H., Taha N.M., Elfeky M.S. (2022). Nanocurcumin alleviates inflammation and oxidative stress in LPS-induced mastitis via activation of Nrf2 and suppressing TLR4-mediated NF-κB and HMGB1 signaling pathways in rats. Environ. Sci. Pollut. Res., 1: 1–2.
- Li B., Wan Z., Wang Z., Zuo J., Xu Y., Han X., Phouthapane V., Miao J. (2020). TLR2 signaling pathway combats Streptococcus uberis infection by inducing mitochondrial reactive oxygen species production. Cells, 9: 494.
- Li K., Ran X., Zeng Y., Li S., Hu G., Wang X., Li Y., Yang Z., Liu J., Fu S. (2023 a). Maslinic acid alleviates LPS-induced mice mastitis by inhibiting inflammatory response, maintaining the integrity of the blood-milk barrier and regulating intestinal flora. Int. Immunopharmacol., 122: 110551.
- Li K., Yang M., Jia L., Tian M., Du J., Wu Y., Yuan L., Li L., Ma Y. (2023 b). The prevention effect of Lactobacillus plantarum 17–5 on Escherichia coli-induced mastitis in mice. Probiotics Antimicrob. Proteins, 15: 1644–1652.
- Li K., Yang M., Tian M., Jia L., Du J., Wu Y., Li L., Yuan L., Ma Y. (2022). Lactobacillus plantarum 17–5 attenuates Escherichia coli-induced inflammatory responses via inhibiting the activation of the NF-κB and MAPK signalling pathways in bovine mammary epithelial cells. BMC Vet. Res., 18: 250.
- Li K., Yang M., Tian M., Jia L., Wu Y., Du J., Yuan L., Li L., Ma Y. (2024). The preventive effects of Lactobacillus casei 03 on Escherichia coli-induced mastitis in vitro and in vivo. J. Inflamm., 21: 5.
- Li M., Lu G., Ma X., Wang R., Chen X., Yu Y., Jiang C. (2022). Anti-inflammation of isoliquiritigenin via the inhibition of NF-κB and MAPK in LPS-stimulated MAC-T cells. BMC Vet. Res., 18: 320.
- Li M., Wang Z., Fu S., Sun N., Li W., Xu Y., Han X., Zhang J., Miao J. (2023). Taurine reduction of injury from neutrophil infiltration ameliorates Streptococcus uberis-induced mastitis. Int. Immunopharmacol., 124: 111028.
- Li S., Li X., Yang T., Pan L., Xu Y., Wang L., Jiang M., Zhou J., Sun C., Yao J., Zhang G. (2022). Jingfang granules alleviate LPS-induced mastitis by inhibiting inflammation, protecting the blood-milk barrier structure and regulating cell apoptosis. Pharmacol. Res. Mod. Chin. Med., 2: 100072.
- Li Y., Wang M., Liu W., Geng M., Asiri M., Alzahrani F.M., Alzahrani K.J., Ma Q., Wang C., Khan M.Z. (2025). Targeting the gut–mammary axis for understanding mastitis pathogenesis and therapeutic strategies. Vet. Sci., 12: 1049.
- Lin X., Zhao Z., Cai Y., He Y., Wang J., Liu N., Qin Y., Wu Y. (2024). MyD88 deficiency in mammary epithelial cells attenuates lipopolysaccharide (LPS)-induced mastitis in mice. Biochem. Biophys. Res. Commun., 739: 150569.
- Liu K., Qiu S., Fang L., Cui L., Dong J., Guo L., Meng X., Li J., Wang H. (2024). The effect of meloxicam on inflammatory response and oxidative stress induced by Klebsiella pneumoniae in bovine mammary epithelial cells. Vet. Sci., 11: 607.
- Liu R., Zhu H., Zhao J., Wu X., Lu X., Xu T., Yang Z. (2022). Lycium barbarum polysaccharide inhibits E. coli-induced inflammation and oxidative stress in mammary epithelial cells of dairy cows via SOCS3 activation and MAPK suppression. Agriculture, 12: 598.
- Luo H., Li Y., Xie J., Xu C., Zhang Z., Li M., Xia B., Shi Z., Lin L. (2024). Effect and mechanism of Prunella vulgaris L. extract on alleviating lipopolysaccharide-induced acute mastitis in protecting the blood-milk barrier and reducing inflammation. J. Ethnopharmacol., 328: 117998.
- Lv X., Xie Z., Wang H., Lu G., Li M., Chen D., Lin T., Jiang C. (2024). In vivo and in vitro anti-inflammation of Rhapontici Radix extract on mastitis via TMEM59 and GPR161. J. Ethnopharmacol., 333: 118462.
- Lv X., Long Q., Kang Y., Lin T., Jiang C. (2025). Combined effects of quinic acid and isochlorogenic acid B on LPS-induced inflammation and pyroptosis in MAC-T cells and mouse mammary glands. Front. Vet. Sci., 12: 1476302.
- Lyu C.C., Che H.Y., Meng Y., Meng Y., Wu H.Y., Zhang J.B., Zhang Y.H., Yuan B. (2024). CGA alleviates LPS-induced inflammation and milk fat reduction in BMECs through the NF-κB signaling pathway. Heliyon, 10: e25004.
- Ma F., Yang S., Zhou M., Lu Y., Deng B., Zhang J., Fan H., Wang G. (2022). NADPH oxidase-derived reactive oxygen species production activates the ERK1/2 pathway in neutrophil extracellular traps formation by Streptococcus agalactiae isolated from clinical mastitis bovine. Vet. Microbiol., 268: 109427.
- Ma H., Zhang Y., Wang J., Guo W., Hu G., Xie S., Yang Z., Liu J., Fu S. (2021). Palmatine attenuates LPS-induced inflammatory response in mouse mammary epithelial cells through inhibiting ERK1/2, P38 and Akt/NF-кB signalling pathways. J. Anim. Physiol. Anim. Nutr., 105: 183–190.
- Ma Q., Wei Y., Meng Z., Chen Y., Zhao G. (2022). Effects of water extract from Artemisia argyi leaves on LPS-induced mastitis in mice. Animals, 12: 907.
- Ma X., Li M., Lu G., Wang R., Wei Y., Guo Y., Yu Y. and Jiang C. (2021). Anti-inflammation of epicatechin mediated by TMEM35A and TMPO in bovine mammary epithelial cell line cells and mouse mammary gland. J. Dairy Sci., 104: 12925–12938.
- Ma X., Wang R., Yu S., Lu G., Yu Y., Jiang C. (2020). Anti-inflammatory activity of oligomeric proanthocyanidins via inhibition of NF-κB and MAPK in LPS-stimulated MAC-T cells. J. Microbiol. Biotechnol., 30: 1458.
- Malik M.U., Hashmi N., Khan M., Aabdin Z.U., Sami R., Aljahani A.H., Al-Eisa R.A., Moawadh M.S., Algehainy N.A. (2023). Nutraceutical effect of resveratrol on the mammary gland: Focusing on the NF-κB/Nrf2 signaling pathways. Animals, 13: 1266.
- Muhammad A., Aftab S., Arshad Z., Chen Y., Wang Y., Yang M., Umar T., Guo M., Deng G. (2020). Hederacoside-C inhibition of Staphylococcus aureus-induced mastitis via TLR2 & TLR4 and their downstream signaling NF-κB and MAPKs pathways in vivo and in vitro. Inflammation, 43: 579–594.
- Puerto M.A., Shepley E., Cue R.I., Warner D., Dubuc J., Vasseur E. (2021). The hidden cost of disease: I. Impact of the first incidence of mastitis on production and economic indicators of primiparous dairy cows. J. Dairy Sci., 104: 7932–7943.
- Qin J., Cai Y., Wang Y., Sun N., An N., Yang J., Li Y., Qin S., Du R. (2024). Mitigative effect and mechanism of caffeic acid combined with umbilical cord-mesenchymal stem cells on LPS-induced mastitis. J. Agric. Food Chem., 72: 23271–23285.
- Qiu M., Feng L., Yu Z., Zhao C., Gao S., Bao L., Zhang N., Fu Y., Hu X. (2022). Probiotic Enterococcus mundtii H81 inhibits the NF-κB signaling pathway to ameliorate Staphylococcus aureus-induced mastitis in mice. Microb. Pathog., 164: 105414.
- Qudratullah, Muhammad G., Jamil T., Rashid I., Ullah Q., Saqib M. (2022). Efficacy evaluation of a combined hemorrhagic septicemia–mastitis vaccine in dairy cows and buffaloes. Animals, 12: 706.
- Rainard P., Gilbert F.B., Germon P. (2022). Immune defenses of the mammary gland epithelium of dairy ruminants. Front. Immunol., 13: 1031785.
- Rakib M.R., Zhou M., Xu S., Liu Y., Khan M.A., Han B., Gao J. (2020). Effect of heat stress on udder health of dairy cows. J. Dairy Res., 87: 315–321.
- Rasmussen P., Barkema H.W., Osei P.P., Taylor J., Shaw A.P., Conrady B., Chaters G., Muñoz V., Hall D.C., Apenteng O.O., Rushton J. (2024). Global losses due to dairy cattle diseases: A comorbidity-adjusted economic analysis. J. Dairy Sci., 107: 6945–6970.
- Richardet M., Solari H.G., Cabrera V.E., Vissio C., Agüero D., Bartolomé J.A., Bó G.A., Bogni C.I., Larriestra A.J. (2023). The economic evaluation of mastitis control strategies in Holstein-Friesian dairy herds. Animals, 13: 1701.
- Rollin E., Dhuyvetter K.C., Overton M.W. (2015). The cost of clinical mastitis in the first 30 days of lactation: An economic modeling tool. Prev. Vet. Med., 122: 257–264.
- Sadam Jamal M., Rahman S.U., Khan M., Qadeer A., Mahmoud M.H. (2024) Genomic diversity and nutritional analysis of multi-drug resistant extended spectrum β-lactamase producing-Klebsiella pneumoniae genes isolated from mastitic cattle milk in district Peshawar, Pakistan. Heliyon, 10(15).
- Samaraweera A.M., van der Werf J.H., Boerner V., Hermesch S. (2022). Economic values for production, fertility and mastitis traits for temperate dairy cattle breeds in tropical Sri Lanka. J. Anim. Breed. Genet., 139: 330–341.
- Senthamilan S., Aggarwal A., Grewal S., Rani S., Vats P., Pal P., Jaswal S., Arya A., Alhussien M.N. (2023). Pre-treatment but not co-treatment with vitexin alleviates hyperthermia induced oxidative stress and inflammation in buffalo mammary epithelial cells. J. Reprod. Immunol., 158: 103979.
- Shen J., Yang F., Wang G., Mou X., Li J., Ding X., Wang X., Li H. (2023). Paeoniflorin alleviates inflammation in bovine mammary epithelial cells induced by Staphylococcus haemolyticus through TLR2/NF-κB signaling pathways. Res. Vet. Sci., 156: 95–103.
- Sindhu P., Magotra A., Dhundwal K., Chaudhary P., Garg A.R. (2025). Association of toll like receptor-4 immune gene polymorphism with production, clinical mastitis and fertility disorders in Hardhenu (Bos taurus × Bos indicus) cattle. Nucleus, DOI: 10.1007/s13237-025-00568-9
- Soni S., De U.K., Gandhar J.S., Sarkar V.K., Saminathan M., Agarwal R.K., Patra M.K., Singh B.R., Kumar A., Bandyopadhyay S. (2025). Diflunisal attenuates acute inflammatory responses through inhibition of NF-κB signaling pathway in Staphylococcus aureus-induced mastitis of lactating mouse model. Microb. Pathog., 199: 107260.
- Srithanasuwan A., Pangprasit N., Mektrirat R., Suriyasathaporn W., Chuammitri P. (2024). Divergent immune responses to minor bovine mastitis-causing pathogens. Vet. Sci., 11: 262.
- Sun W.J., Wu E.Y., Zhang G.Y., Xu B.C., Chen X.G., Hao K.Y., Wang Y., He L.Z., Lv Q.Z. (2022). Total flavonoids of Abrus cantoniensis inhibit CD14/TLR4/NF-κB/MAPK pathway expression and improve gut microbiota disorders to reduce lipopolysaccharide-induced mastitis in mice. Front. Microbiol., 13: 985529.
- Sun X., Luo S., Jiang C., Tang Y., Cao Z., Jia H., Xu Q., Zhao C., Loor J.J., Xu C. (2020). Sodium butyrate reduces bovine mammary epithelial cell inflammatory responses induced by exogenous lipopolysaccharide, by inactivating NF-κB signaling. J. Dairy Sci., 103: 8388–8397.
- Tang X., Liu C., Li T., Lin C., Hao Z., Zhang H., Zhao G., Chen Y., Guo A., Hu C. (2020). Gambogic acid alleviates inflammation and apoptosis and protects the blood-milk barrier in mastitis induced by LPS. Int. Immunopharmacol., 86: 106697.
- Tao L., Liu K., Li J., Zhang Y., Cui L., Dong J., Meng X., Zhu G., Wang H. (2022). Selenomethionine alleviates NF-κB-mediated inflammation in bovine mammary epithelial cells induced by Escherichia coli by enhancing autophagy. Int. Immunopharmacol., 110: 108989.
- Tommasoni C., Fiore E., Lisuzzo A., Gianesella M. (2023). Mastitis in dairy cattle: On-farm diagnostics and future perspectives. Animals, 13: 2538.
- Tong X., Barkema H.W., Nobrega D.B., Xu C., Han B., Zhang C., Yang J., Li X., Gao J. (2025). Virulence of bacteria causing mastitis in dairy cows: A literature review. Microorganisms, 13: 167.
- Wang M., Jin L. (2023). Quyu Xiaozhong recipe exerts anti-inflammatory effect in acute mastitis by inhibiting TLR4/NF-κB signal pathway. Trop. J. Pharm. Res., 22: 981–986.
- Wang J., Gao Y., Cheng C., Li Y., Zhang X., Yao D., Zhang Y. (2024). Dangguibuxue decoction protects against lipopolysaccharides-induced mastitis in bovine mammary epithelial cells in vitro. J. Anim. Sci. Technol., DOI: 10.5187/jast.2024.e63
- Wang J., Cheng C., Gao Y., Li Y., Zhang X., Yao D., Zhang Y. (2025 a). Danggui Buxue decoction alleviates inflammation and oxidative stress in mice with Escherichia coli-induced mastitis. Vet. Sci., 12: 227.
- Wang L., Yang F., Wei X.J., Luo Y.J., Guo W.Z., Zhou X.Z., Guo Z.T. (2019). Prevalence and risk factors of subclinical mastitis in lactating cows in Northwest China. Isr. J. Vet. Med., 74: 17–22.
- Wang X., Lai J., Xu F., Liu M. (2025 b). Network pharmacology and molecular docking: Exploring the mechanism of peppermint in mastitis prevention and treatment in dairy cows. Vet. Sci., 12: 129.
- Wu F., Du T., Jiang X., Liu S., Cheng Y., Zhang Z., Miao W., Wang T. (2024). Lactococcus garvieae exerts a critical role in inducing inflammation in dairy mastitis by triggering NLRP3 inflammasome-mediated pyroptosis in MAC-T cells. World J. Microbiol. Biotechnol., 40: 132.
- Xiao J., Khan M.Z., Ma Y., Alugongo G.M., Ma J., Chen T., Khan A., Cao Z. (2021). The antioxidant properties of selenium and vitamin E; their role in periparturient dairy cattle health regulation. Antioxidants, 10: 1555.
- Xie Y., Li X., Xu D., He D., Wang J., Bi J., Liu J., Fu S. (2024). Hordenine alleviates lipopolysaccharide-induced mastitis by suppressing inflammation and oxidative stress, modulating intestinal microbiota, and preserving the blood–milk barrier. J. Agric. Food Chem., 72: 21503–21519.
- Xu J., Jia Z., Chen A., Wang C. (2020). Curcumin ameliorates Staphylococcus aureus-induced mastitis injury through attenuating TLR2-mediated NF−κB activation. Microb. Pathog., 142: 104054.
- Xu P., Xu X., Fotina H., Fotina T. (2023). Anti-inflammatory effects of chlorogenic acid from Taraxacum officinale on LTA-stimulated bovine mammary epithelial cells via the TLR2/NF-κB pathway. PLoS ONE, 18: e0282343.
- Xu T., Liu R., Lu X., Wu X., Heneberg P., Mao Y., Jiang Q., Loor J., Yang Z. (2022). Lycium barbarum polysaccharides alleviate LPS-induced inflammatory responses through PPARγ/MAPK/NF-κB pathway in bovine mammary epithelial cells. J. Anim. Sci., 100: skab345.
- Yan H., Zhou T., Wang Y., Liu Z., Ali I., Sheng L., Jiang Q., Li T., Xiang M., Li P., Zhang W. (2023). CDK5RAP3, a key defender of udder, modulates NLRP3 inflammasome activation by regulating autophagolysosome degradation in S. agalactiae-infected mastitis. Int. J. Biol. Macromol., 234: 123714.
- Yan S., Ju X., Lao J., Wen Z., Yong Y., Li Y., Li Y. (2024). Overexpression of the Mas1 gene mitigated LPS-induced inflammatory injury in mammary epithelial cells by inhibiting the NF-κB/MAPKs signaling pathways. Front. Vet. Sci., 11: 1446366.
- Yang F., Yuan L., Xiang M., Jiang Q., Zhang M., Chen F., Tong J., Huang J., Cai Y. (2022). A novel TLR4-SYK interaction axis plays an essential role in the innate immunity response in bovine mammary epithelial cells. Biomedicines, 11: 97.
- Yang J., Liu Y., Lin C., Yan R., Li Z., Chen Q., Zhang H., Xu H., Chen X., Chen Y., Guo A. (2022). Regularity of toll-like receptors in bovine mammary epithelial cells induced by Mycoplasma bovis. Front. Vet. Sci., 9: 846700.
- Yang M., Han J., Yan Z., Li K. (2025). Paeonol attenuates LPS-induced inflammatory injury in mastitis by regulating the MAPK and Nrf2 signaling pathways. Res. Vet. Sci., 182: 105481.
- Yang X., Li X., Guo L., Gong P., Qian Y., Zhang S., Liu B., Guo W., Bao H., Mao W. (2025). Investigating the role of the mPGES-PGE2-EP4 pathway in E. coli-induced mastitis in dairy cows: Insights for non-antibiotic therapeutic strategies. Front. Vet. Sci., 12: 1628028.
- Yanthi N.D., Anggraeni A., Said S., Saputra S., Soejoedono R.D., Muladno M., Herlina N., Fauziah I., Nugroho H.A., Nasrulloh M.F., Tiffarent R. (2025). Differential expression of TLR and CXCR genes in mammary HC11 cells challenged with Bacillus cereus and Bacillus subtilis: Implications for mastitis resistance. Vet. World, 18: 1014.
- Yu C., Zhang C., Huai Y., Liu D., Zhang M., Wang H., Zhao X., Bo R., Li J., Liu M. (2024). The inhibition effect of caffeic acid on NOX/ROS-dependent macrophages M1-like polarization contributes to relieve the LPS-induced mice mastitis. Cytokine, 174: 156471.
- Zhang B., Chen N., Yu X., Li J., Dong W., Zhang Y., Zhao X., Zhang Q. (2025). Role of CORO1A in regulating immune homeostasis of mammary glands and its contribution to clinical mastitis development in dairy cows. Biomolecules, 15: 827.
- Zhang J., Xin L., Zhang A., Song J. (2025). NF-kappaB is involved exclusively under inflammatory conditions in the regulation of cathelicidin 3 expression in bovine mammary glands through phosphorylation of p65. J. Anim. Sci., 103: skaf112.
- Zhang K., Zhang M., Su H., Zhao F., Wang D., Zhang Y., Cao G., Zhang Y. (2024). Regulation of inflammatory responses of cow mammary epithelial cells through MAPK signaling pathways of IL-17A cytokines. Animals, 14: 1572.
- Zhang K., Zhang M., Su H., Zhao F., Wang D., Cao G., Zhang Y. (2025). Regulation of LPS-induced inflammatory responses in bovine mammary epithelial cells via TLR4-mediated NF-κB and MAPK signaling pathways by lactoferrin. Life, 15: 69.
- Zhang Y., Ding Y., Liang J., Zhang K., Su H., Wang D., Zhang M., Zhao F., Sun Z., Wu Z., Wang F. (2025). Impact of Escherichia coli and lipopolysaccharide on the MAPK signaling pathway, MMPs, TIMPs, and the uPA system in bovine mammary epithelial cells. Int. J. Mol. Sci., 26: 3893.
- Zhao J., Xu L., Lv L., Wang L., Wang X., Liang C., Wang C., Qiu Y., Pei X. (2023). Network pharmacology and in vivo and in vitro experiments to determine the mechanism behind the effects of Jiawei Yanghe decoction via TLR4/Myd88/NF-κB against mastitis. Heliyon, 9: e21177.
- Zhu H., Cao W., Huang Y., Karrow N.A., Yang Z. (2023). Involvement of pyocyanin in promoting LPS-induced apoptosis, inflammation, and oxidative stress in bovine mammary epithelium cells. Agriculture, 13: 2192.
DOI: https://doi.org/10.2478/aoas-2026-0004 | Journal eISSN: 2300-8733 (formerly 1642-3402) | Journal ISSN: 1642-3402
Language: English
Submitted on: Sep 11, 2025
Accepted on: Dec 5, 2025
Published on: Oct 5, 2026
Published by: National Research Institute of Animal Production
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
Related subjects:
© 2026 Xuewei Fan, Xin Jiang, Qudrat Ullah, Abdul Qadeer, Safia Obaidur Rab, Fuad M. Alzahrani, Khalid J. Alzahrani, Khalaf F. Alsharif, Muhammad Zahoor Khan, published by National Research Institute of Animal Production
This work is licensed under the Creative Commons Attribution 4.0 License.