Rutin protects against lipopolysaccharide-induced mastitis by inhibiting the activation of the NF-κB signaling pathway and attenuating endoplasmic reticulum stress
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Rutin, found widely in traditional Chinese medicine materials, is used to treat eye swelling and pain, hypertension, and hyperlipidemia. In the present study, a mouse mastitis model induced by lipopolysaccharide (LPS) was established to explore rutin’s inhibitory mechanism on mastitis via nuclear factor kappa B (NF-κB) inflammatory signaling and the relationship between NF-κB signaling and endoplasmic reticulum (ER) stress. Mice were divided into six groups: Control group, LPS model group, LPS + rutin (25, 50, and 100 mg/kg) and LPS + dexamethasone (DEX) group. DEX, rutin, and PBS (control and LPS groups) were administered 1 h before and 12 h after perfusion of LPS. After LPS stimulation for 24 h, to evaluate rutin’s therapeutic effect on mastitis, the mammary tissues of each group were collected to detect histopathological injury, tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 mRNA and protein levels; and glucose-regulated protein, 78 kDa (GRP78) protein levels. The protein and mRNA levels of TNF-α, IL-1β, and IL-6 in the LPS + rutin group were significantly lower than those in the LPS model group. Similarly, p50/p105, phosphorylated (p)-p65/p65 and p-inhibitor of nuclear factor kappa b kinase subunit beta (p-IKKβ)/IKKβ ratios in the LPS + rutin group (50 mg/kg) and LPS + rutin group (100 mg/kg) decreased significantly. GRP78 protein expression was significantly higher in LPS + rutin group (100 mg/kg). The structure of mammary tissue became gradually more intact and vacuolization of acini decreased as the rutin concentration increased. The nuclear quantity of p65 in the LPS + rutin group decreased significantly in a rutin dose-dependent manner. Rutin had an anti-inflammatory effect in the LPS-induced mouse mastitis model, manifested by inhibition of NF-κB pathway activation and attenuation of ER stress.
KeywordsRutin Mastitis Mice NF-κB signaling pathway ER stress
This work was supported by the Anhui Agricultural University College Students Innovation and Entrepreneurship Training Program Innovative Training Project Foundation (Grant Numbers 201710364061 and 201710364017).
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Conflict of interest
The authors declare that they have no conflict of interest.
- Chen H, Mo X, Yu J, Huang Z (2013) Alpinetin attenuates inflammatory responses by interfering toll-like receptor 4/nuclear factor kappa B signaling pathway in lipopolysaccharide-induced mastitis in mice. Int Immunopharmacol 17:26–32. https://doi.org/10.1016/j.intimp.2013.04.030 CrossRefPubMedGoogle Scholar
- Gautam R, Singh M, Gautam S, Rawat JK, Saraf SA, Kaithwas G (2016) Rutin attenuates intestinal toxicity induced by Methotrexate linked with anti-oxidative and anti-inflammatory effects. BMC Complement Altern Med 16:99. https://doi.org/10.1186/s12906-016-1069-1 CrossRefPubMedPubMedCentralGoogle Scholar
- Moutinho MSS, Aragao S, Carmo D, Casaca F, Silva S, Ribeiro J, Sousa H, Pires I, Queiroga F, Colaco B, Medeiros R, Oliveira PA, Lopes C, Bastos M, DA Costa RMG (2018) Curcumin and rutin down-regulate cyclooxygenase-2 and Reduce tumor-associated Inflammation in HPV16-transgenic mice. Anticancer Res 38:1461–1466. https://doi.org/10.21873/anticanres.12371 PubMedCrossRefGoogle Scholar
- Reshi AA, Husain I, Bhat SA, Rehman MU, Razak R, Bilal S, Mir MR (2015) Bovine mastitis as an evolving disease and its impact on the dairy industry. Solid State Phenom 7:194–2262375Google Scholar
- Taniguchi F, Uegaki T, Nakamura K, Mon KY, Harada T, Ohbayashi T, Harada T (2018) Inhibition of IAP (inhibitor of apoptosis) proteins represses inflammatory status via nuclear factor-kappa B pathway in murine endometriosis lesions. Am J Reprod Immunol 79:e12780. https://doi.org/10.1111/aji.12780 CrossRefGoogle Scholar