title: Polydatin ameliorates Staphylococcus aureus-induced mastitis in mice via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB pathway.
abstract: Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureus-induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation. Furthermore, PD treatment dose-dependently decreased the levels of TNF-α, IL-1β, IL-6 and IL-8 in the mammary gland tissues. PD treatment also dose-dependently decreased the expression of TLR2, MyD88, IRAK1, IRAK4 and TRAF6 as well as the phosphorylation of TAK1, MKK3/6, p38 MAPK, IκB-α and NF-κB in the mammary gland tissues. In mouse mammary epithelial cells (mMECs) infected by S aureus in vitro, pretreatment with PD dose-dependently suppressed the upregulated pro-inflammatory cytokines and signaling proteins, and the nuclear translocation of NF-κB p65 and AP-1. A TLR2-neutralizing antibody mimicked PD in its suppression on S aureus-induced upregulation of MyD88, p-p38 and p-p65 levels in mMECs. PD (50, 100 μg/mL) affected neither the growth of S aureus in vitro, nor the viability of mMECs. In conclusion, PD does not exhibit antibacterial activity against S aureus, its therapeutic effects in mouse S aureus-induced mastitis depend on its ability to down-regulate pro-inflammatory cytokine levels via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB signaling pathway.
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Kang-Feng
authors.initials: KF
authors.lastname: Jiang
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Gan-Zhen
authors.initials: GZ
authors.lastname: Deng
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Hai-Chong
authors.initials: HC
authors.lastname: Wu
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Yin
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Chang-Wei
authors.initials: CW
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Peng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008413:Mastitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology; D013267:Stilbenes / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005960:Glucosides; D018836:Inflammation Mediators; D016328:NF-kappa B; D013267:Stilbenes; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D003907:Dexamethasone; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases; C058229:polydatin