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Albiflorin ameliorates inflammation and oxidative stress by regulating the NF-κB/NLRP3 pathway in Methotrexate-induced enteritis

氧化应激 丙二醛 化学 髓过氧化物酶 超氧化物歧化酶 药理学 炎症 细胞凋亡 活性氧 谷胱甘肽 甲氨蝶呤 NF-κB 免疫学 医学 生物化学
作者
Haihua Zhang,Jing Wang,Wuying Lang,Hongli Liu,Zhiqiang Zhang,Tonglei Wu,Hongqiang Li,Liya Bai,Qiumei Shi
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:109: 108824-108824 被引量:34
标识
DOI:10.1016/j.intimp.2022.108824
摘要

Methotrexate (MTX) treats various diseases but also damages intestinal barrier and leads to enteritis. Albiflorin (ALB) has a variety of pharmacological effects, including antioxidant, anti-inflammation and anti-apoptosis. In the present study, we evaluated the therapeutic effect of ALB on MTX-induced enteritis and investigated the possible mechanisms involved. Male SD rats were intraperitoneally injected with 7 mg/kg MTX for three consecutive days to establish the enteritis model. ALB (20 or 40 mg/kg/day) was intragastrically administrated since two days prior MTX treatment and lasted for six days. We found that ALB treatment increased body weight and intestinal weight of rats with MTX injection. The disease activity index (DAI) score was also decreased after ALB administration. In histological examination, ALB treatment attenuated inflammatory cells infiltration and promoted survival of goblet cells. In detection of inflammatory-associated factors, ALB treatment decreased CD68+ cells infiltration, inhibited myeloperoxidase activity, and suppressed intercellular cell adhesion molecule-1 and cyclooxygenase-2 expression. Additionally, ALB reduced malondialdehyde, glutathione levels, inhibited superoxide dismutase activity and suppressed reactive oxygen species production. Moreover, ALB treatment effectively inhibited NLRP3, as well as caspase 1 p20 and interleukin (IL)-1β and 18 expression. Finally, nuclear factor-κB (NF-κB) p65 phosphorylation and nuclear translocation were also demonstrated to be blocked upon ALB treatment. In conclusion, our findings indicated that ALB alleviated MTX-induced enteritis via inhibiting the NF-κB/NLRP3 pathway.
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