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

Abstract

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.

• Authors: Baoru Qiao, Hao Wang, Cheng Wang, Minglu Liang, Kai Huang, Yiqing Li
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 666 Pg. 99-106 (05 15 2019) ISSN: 1096-0384 [Electronic] United States
• PMID: 30946805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Benzylisoquinolines
• Cytokines
• Inflammation Mediators
• Lipopolysaccharides
• NF-kappa B
• Tetrahydroisoquinolines
• dauricine

Topics

• Acute Lung Injury (drug therapy, etiology, pathology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Benzylisoquinolines (pharmacology)
• Cytokines (antagonists & inhibitors, metabolism)
• Humans
• Inflammation (drug therapy, etiology, metabolism)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Lipopolysaccharides (toxicity)
• Macrophages, Peritoneal (drug effects, metabolism, pathology)
• Medicine, Chinese Traditional
• Mice
• Mice, Inbred C57BL
• NF-kappa B (antagonists & inhibitors)
• Phytotherapy
• RAW 264.7 Cells
• Tetrahydroisoquinolines (pharmacology)