Anti-inflammatory effects of higenamine (Hig) on LPS-activated mouse microglia (BV2) through NF-κB and Nrf2/HO-1 signaling pathways.

Abstract

Microglia are the most widely equipped protective cells in the brain and play a pivotal role in the development of neurological diseases. Inflammatory response and oxidative stress are critical risk factors in the activation of microglia which may cause various neurological diseases. Higenamine (Hig), a plant-based alkaloid and isolated from Aconite tuber, exhibits various properties and is mainly applied to treat heart failure. In addition, Hig expresses potential protective effects for neurodegenerative diseases. However, the effects and mechanisms of Hig on lipopolysaccharide (LPS) activated mouse microglia has not been fully explored. Therefore, we evaluated the anti-inflammatory effects of Hig on LPS-activated BV2 microglia and revealed the underlying mechanisms. Our data showed that Hig significantly inhibited the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS) as well as NO (mediated by iNOS) and PGE2 (mediated by COX2) in LPS-activated BV2 cells. Then we found that Hig suppressed NF-κB signaling pathway by inhibiting nuclear translocation of NF-κB/p65 subunit as well as degradation and phosphorylation of IκBα in cytoplasm, and the effect of Hig was intimately related to NF-κB inhibitor BAY-11-7082. Furthermore, we found that the anti-inflammatory effect of Hig were accompanied by the promotion of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor-2 (Nrf2) expression, which was partly reversed by protoporphyrin (SnPP) and Nrf2 siRNA, respectively. Taken together, our results demonstrated that Hig expressed significant anti -inflammatory and -oxidative effects by inhibiting NF-κB and activating Nrf2/HO-1 signaling pathways.

• Authors: Songwei Yang, Shifeng Chu, Qidi Ai, Zhao Zhang, Yan Gao, Meiyu Lin, Yingjiao Liu, Yaomei Hu, Xun Li, Ye Peng, Yawen Pan, Qinghui He, Naihong Chen
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 85 Pg. 106629 (Aug 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32535536 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Alkaloids
• Anti-Inflammatory Agents
• Lipopolysaccharides
• Membrane Proteins
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, mouse
• Reactive Oxygen Species
• Tetrahydroisoquinolines
• Nitric Oxide
• Heme Oxygenase-1
• Hmox1 protein, mouse
• higenamine

Topics

• Alkaloids (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Line
• Heme Oxygenase-1 (metabolism)
• Lipopolysaccharides
• Membrane Proteins (metabolism)
• Mice
• Microglia (drug effects, metabolism)
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Tetrahydroisoquinolines (pharmacology)