Tabersonine attenuates lipopolysaccharide-induced acute lung injury via suppressing TRAF6 ubiquitination.

Abstract

Sepsis caused by Gram-negative bacteria is one of major causes for the progression of acute lung injury (ALI) with limited treatment and effective medicines. Tabersonine is an indole alkaloid mainly isolated from Catharanthus roseus, and a potential drug candidate for treatment of cancer and Alzheimer's disease (AD), however, its anti-inflammatory effect has not been revealed. In this study, we reported that tabersonine ameliorated lipopolysaccharides (LPS)-induced ALI in vivo and inhibited LPS-mediated macrophage activation in vitro. By using murine ALI model, we found that tabersonine significantly attenuated LPS-induced pathological injury in the lung. Tabersonine also inhibited LPS-mediated neutrophil infiltration, elevation of MPO activity and the production of TNF-α, IL-6 and IL-1β. Furthermore, tabersonine inhibited LPS-induced the production of pro-inflammatory mediators such as iNOS, NO and cytokines by suppressing NF-κB and p38 MAPK/MK2 signaling cascades. Tabersonine reduced the K63-linked polyubiquitination of TRAF6. Taken together, these results suggested that tabersonine has anti-inflammatory activities in vitro and in vivo, and is a potential therapeutic candidate for the treatment of ALI/ARDS.

• Authors: Depeng Zhang, Xiaozong Li, Yudong Hu, Hongchao Jiang, Yaxian Wu, Yunhe Ding, Kaikai Yu, Huiqiong He, Jingsong Xu, Lei Sun, Feng Qian
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 154 Pg. 183-192 (08 2018) ISSN: 1873-2968 [Electronic] England
• PMID: 29746822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Indole Alkaloids
• Inflammation Mediators
• Lipopolysaccharides
• Quinolines
• TNF Receptor-Associated Factor 6
• tabersonine

Topics

• Acute Lung Injury (chemically induced, metabolism, prevention & control)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Indole Alkaloids (pharmacology, therapeutic use)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Lipopolysaccharides (toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Quinolines (pharmacology, therapeutic use)
• Random Allocation
• TNF Receptor-Associated Factor 6 (antagonists & inhibitors, metabolism)
• Ubiquitination (drug effects, physiology)