Capillarisin augments anti-oxidative and anti-inflammatory responses by activating Nrf2/HO-1 signaling.

Abstract

Capillarisin is a naturally isolated chromone, which is one of the major bioactive constituents of Artemisia capillaries. Capillarisin has antioxidant, anti-inflammatory, and anti-tumor potential, but the underlying molecular mechanisms remain largely unclear. In the present study, we demonstrate that the transcription factor nuclear factor E2-related factor-2 (Nrf2) is activated by capillarisin in neuroblastoma SH-SY5Y cells and microglial BV2 cells. Capillarisin leads to Nrf2 phosphorylation, subsequent activation of antioxidant response element (ARE)-mediated transcription, and up-regulation of downstream molecules, such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1. Capillarisin protects SH-SY5Y cells from 6-hydroxydopamine-induced oxidative stress and attenuates inflammatory responses in lipopolysaccharide-treated BV2 cells. The cytoprotective and anti-inflammatory effects of capillarisin are significantly abolished in cells transfected with specific Nrf2 or HO-1 siRNA, suggesting that these pharmacological properties of capillarisin are primarily due to increased HO-1 activity. Capillarisin induces the activation of c-Jun N-terminal kinase in SH-SY5Y and BV2 cells, which is responsible for Nrf2 phosphorylation and HO-1 upregulation. Together, this study demonstrates that capillarisin is a potential activator of the Nrf2/ARE-dependent pathway and could be an attractive candidate for the regulation of oxidative stress and inflammatory responses in the brain.

• Authors: Jinhee Kim, Juhee Lim, Bok Yun Kang, Kiwon Jung, Hyun Jin Choi
• Journal: Neurochemistry international (Neurochem Int) Vol. 105 Pg. 11-20 (May 2017) ISSN: 1872-9754 [Electronic] England
• PMID: 28161468 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Chromones
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• capillarisin
• HMOX1 protein, human
• Heme Oxygenase-1

Topics

• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Heme Oxygenase-1 (metabolism)
• Humans
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects, physiology)
• Signal Transduction (drug effects, physiology)