Activation of Nrf2 signaling by Icariin protects against 6-OHDA-induced neurotoxicity.

Abstract

Nerve damage is the main pathogenesis of neurodegenerative diseases. Recently, in search for a promising therapeutic target that could stop neurodegenerative diseases progression, the antioxidant signaling pathway regulated by transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has attracted new hopes. Icariin (ICA) exhibited a battery of pharmacological properties, including antioxidation, anti-aging, and anti-inflammation activities. Recent studies indicate ICA conferred neuroprotection against brain ischemic injury and neurodegenerative diseases. However, the mechanisms underlying ICA-mediated neuroprotection remain unelucidated. This study aimed at analyzing whether ICA evoked neuroprotection against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and the mechanisms of action. ICA protected against 6-OHDA-induced neuronal damage, accompanied by the inhibition of cell apoptosis through the marked decreases in the Bax/Bcl-2 ratio, cytochrome c release, and caspase-3 cleavage. In addition, the activation of Nrf2 signaling pathway was responsible for ICA-mediated neuroprotection. First, ICA relieved reactive oxygen species accumulation and increased superoxide dismutase generation via the activation of Nrf2 signaling. Second, Nrf2 knockdown by siRNA reversed ICA-mediated neuroprotection. Together, these results suggested ICA-mediated neuroprotection might be attributable to the activation of Nrf2 pathway via antioxidative signaling pathways.

• Authors: Li Zhu, DaiDi Li, Ce Chen, GuoQing Wang, JingShan Shi, Feng Zhang
• Journal: Biotechnology and applied biochemistry (Biotechnol Appl Biochem) Vol. 66 Issue 3 Pg. 465-471 (May 2019) ISSN: 1470-8744 [Electronic] United States
• PMID: 30892727 (Publication Type: Journal Article)
• Copyright: © 2019 International Union of Biochemistry and Molecular Biology, Inc.

Chemical References

• Drugs, Chinese Herbal
• Flavonoids
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, rat
• RNA, Small Interfering
• Oxidopamine
• icariin

Topics

• Animals
• Apoptosis (drug effects)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (administration & dosage, pharmacology)
• Flavonoids (administration & dosage, pharmacology)
• NF-E2-Related Factor 2 (agonists, metabolism)
• Neuroprotective Agents (administration & dosage, pharmacology)
• Oxidopamine (toxicity)
• PC12 Cells
• RNA, Small Interfering (antagonists & inhibitors, metabolism)
• Rats
• Signal Transduction (drug effects)
• Structure-Activity Relationship