Rutin protects against lipopolysaccharide-induced mastitis by inhibiting the activation of the NF-κB signaling pathway and attenuating endoplasmic reticulum stress

• DOI: 10.1007/s10787-018-0521-x
• Publication Date: 2018-08-11T07:54:30Z
• Authors: Siyi Su; Xiaoyu Li; Siting Li; Pengfei Ming; Yingying Huang; Yanli Dong; Hongyan Ding; Shibin Feng; Jinchun Li; Xichun Wang; Yu Li; Jinjie Wu
• Keywords: Lipopolysaccharides; 0301 basic medicine; Interleukin-6; MAP Kinase Signaling System; Tumor Necrosis Factor-alpha; Rutin; Interleukin-1beta; Anti-Inflammatory Agents; NF-kappa B; Mastitis; Endoplasmic Reticulum Stress; Protective Agents; 3. Good health; Mice; 03 medical and health sciences; Mammary Glands, Animal; Animals; Female; Endoplasmic Reticulum Chaperone BiP; Signal Transduction

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.