Geraniin Protects against Cerebral Ischemia/Reperfusion Injury by Suppressing Oxidative Stress and Neuronal Apoptosis via Regulation of the Nrf2/HO-1 Pathway.

Abstract

Geraniin, a polyphenol isolated from Phyllanthus amarus, possesses extensive biological and pharmaceutical activities. In this study, we investigated the protective effect against cerebral ischemia/reperfusion (I/R) injury of geraniin and explored its potential mechanism. Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to simulate cerebral I/R injury in vivo, and oxygen-glucose deprivation/reoxygenation (OGD/R) was applied to establish an in vitro model of cerebral I/R injury. In this study, we performed TTC and HE staining and adopted a neurological score method to evaluate the neuroprotective effect of geraniin in vivo and used the CCK-8 assay to assess this effect in vitro. Indices of reactive oxidation capacity were measured in vivo and in vitro to verify the antioxidant capacity of geraniin. TUNEL staining and flow cytometry were applied to measure the apoptosis rate, and Western blotting was performed to assess the expression of apoptosis-related proteins. Finally, the expression of Nrf2 and HO-1 was evaluated in vivo and in vitro by Western blotting. Geraniin significantly reduced the infarct volume, decreased neurological deficit scores, alleviated pathological changes in neurons, and increased the cell survival rate. Geraniin increased the activity of superoxide dismutase (SOD) and decreased the activity of lactate dehydrogenase (LDH) and the contents of malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) in vivo and in vitro. In addition, geraniin significantly reduced the apoptosis. Furthermore, geraniin also evidently increased Nrf2 (total and nuclear) and HO-1 protein expression in vivo and in vitro. Collectively, these results imply that geraniin may exert a protective effect against cerebral I/R injury by suppressing oxidative stress and neuronal apoptosis. The mechanism underlying the protective effect of geraniin is associated with activation of the Nrf2/HO-1 pathway. Our results indicate that geraniin may be a potential drug candidate for the treatment of ischemic stroke.

• Authors: Yuan Yang, Bo He, Xiaochao Zhang, Renhua Yang, Xin Xia, Lu Chen, Rui Li, Zhiqiang Shen, Peng Chen
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 2152746 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35222793 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Yuan Yang et al.

Chemical References

• Antioxidants
• Glucosides
• Hydrolyzable Tannins
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, rat
• Geraniin
• Nitric Oxide Synthase Type I
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat

Topics

• Animals
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Brain Ischemia (drug therapy)
• Cell Survival (drug effects)
• Glucosides (pharmacology, therapeutic use)
• Heme Oxygenase (Decyclizing) (metabolism)
• Hydrolyzable Tannins (pharmacology, therapeutic use)
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Nitric Oxide Synthase Type I (metabolism)
• Oxidative Stress (drug effects)
• PC12 Cells
• Rats
• Reperfusion Injury (drug therapy)
• Signal Transduction (drug effects)