Neohesperidin attenuates cerebral ischemia-reperfusion injury via inhibiting the apoptotic pathway and activating the Akt/Nrf2/HO-1 pathway.

Abstract

Oxidative stress is well known to play a pivotal role in cerebral ischemia-reperfusion injury. On the basis of this fact, antioxidative agents have been demonstrated to be neuroprotective. Neohesperidin (NH) is abundant in citrus flavonoids and possesses reactive oxygen species scavenging activity and neuroprotective effects in vitro. However, little is known about its effects on cerebral ischemia-reperfusion injury and the underlying mechanisms. In this study, we use a rat model of middle cerebral artery occlusion (MCAO) to investigate the neuroprotective effects of NH. NH significantly improved neurological functions and attenuated MCAO-induced infarct volume, pathological changes, and neuronal loss. Moreover, it enhanced antioxidant capacity and suppressed oxidative stress in the brain. NH inhibited the MCAO-induced upregulation of Bax, cytochrome c, and cleaved caspase-9 and -3, as well as the downregulation of Bcl-2. Interestingly, NH treatment upregulated heme oxygenase-1 (HO-1) in a concentration-dependent manner, which was due to the NH-mediated activation of the protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. NH also abolished the MCAO-induced inhibition of the Akt/Nrf2 pathway. In conclusion, NH attenuates cerebral ischemia-reperfusion injury via the inhibition of neuronal apoptosis and oxidative stress through the regulation of the apoptotic pathway and the Akt/Nrf2/HO-1 pathway. NH might be a promising preventive agent for ischemic stroke.

• Authors: Ji-Jun Wang, Ping Cui
• Journal: Journal of Asian natural products research (J Asian Nat Prod Res) Vol. 15 Issue 9 Pg. 1023-37 (Sep 2013) ISSN: 1477-2213 [Electronic] England
• PMID: 23952707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, rat
• Reactive Oxygen Species
• bcl-2-Associated X Protein
• Hesperidin
• Heme Oxygenase-1
• Proto-Oncogene Proteins c-akt
• Caspase 9
• neohesperidin

Topics

• Animals
• Antioxidants (metabolism, pharmacology)
• Apoptosis (drug effects, genetics)
• Brain Ischemia (metabolism, pathology, prevention & control)
• Caspase 9 (genetics, metabolism)
• Heme Oxygenase-1 (drug effects)
• Hesperidin (analogs & derivatives, chemistry, pharmacology)
• Infarction, Middle Cerebral Artery (genetics, pathology)
• Male
• Molecular Structure
• NF-E2-Related Factor 2 (drug effects)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects, genetics)
• Proto-Oncogene Proteins c-akt (drug effects, genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism, pharmacology)
• Reperfusion Injury (prevention & control)
• Up-Regulation (drug effects)
• bcl-2-Associated X Protein (genetics, metabolism, pharmacology)