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Dauricine negatively regulates lipopolysaccharide- or cecal ligation and puncture-induced inflammatory response via NF-κB inactivation

Qiao, Baoru, Wang, Hao, Wang, Cheng, Liang, Minglu, Huang, Kai, Li, Yiqing
Archives of biochemistry and biophysics 2019 v.666 pp. 99-106
Menispermum dauricum, Oriental traditional medicine, bioactive properties, blood serum, herbs, in vitro studies, in vivo studies, inducible nitric oxide synthase, inflammation, interleukin-1beta, interleukin-6, lipopolysaccharides, lungs, macrophages, mice, necrosis, neoplasms, nitric oxide, phosphorylation, prostaglandin synthase, respiratory tract diseases, survival rate, therapeutics, transcription (genetics), transcription factor NF-kappa B, tumor necrosis factor-alpha
Acute lung injury (ALI) is a challenging clinical problem worldwide characterized by severe pulmonary inflammation. Dauricine, extracted from the root of traditional Chinese medicine Menispermum dauricum DC, is employed as anti-inflammatory herbs. In this study, we explored the inhibitory effects of dauricine on lipopolysaccharide (LPS)-induced inflammation in macrophages and LPS- or cecal ligation and puncture (CLP)-induced ALI in C57BL/6 mice. Our in vitro study identified that pretreatment of dauricine dose-dependently inhibited pro-inflammatory cytokines including nitric oxide (NO), interleukin-1β (IL1β), IL6, tumor necrosis factor-α (TNFα), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) in LPS-stimulated macrophages. Moreover, dauricine could suppress LPS-mediated nuclear translocation and transcriptional activity of nuclear factor-kappaB (NF-κB) by suppressing the phosphorylation of NF-κB inhibitors (IκB). In vivo studies, administration of dauricine, especially high-dose dauricine, potently improved the survival rate, reduced the production of pro-inflammatory cytokines in serum, and ameliorated ALI induced by LPS or CLP via blockage of NF-κB activation. Collectively, the present study discovers a new biological effect of dauricine in prevention of inflammation, indicating that dauricine can be served as a potential therapeutic agent to treat inflammatory diseases.