The Synergistic Neuroprotective Effects of Combined Rosuvastatin and Resveratrol Pretreatment against Cerebral Ischemia/Reperfusion Injury.

Abstract

BACKGROUND:

It is well accepted that both rosuvastatin and resveratrol exert neuroprotective effects on cerebral ischemia/reperfusion injury through some common pathways. Resveratrol has also been demonstrated to protect against cerebral ischemia/reperfusion injury through enhancing autophagy. Thus, we hypothesized that combined rosuvastatin and resveratrol pretreatment had synergistic effects on cerebral ischemia/reperfusion injury.

MATERIALS AND METHODS:

Adult male Sprague Dawley rats receiving middle cerebral artery occlusion surgery as animal model of cerebral ischemia/reperfusion injury were randomly assigned to 4 groups: control, resveratrol alone pretreatment, rosuvastatin alone pretreatment, and combined rosuvastatin and resveratrol pretreatment. Rosuvastatin (10 mg/kg) or resveratrol (50 mg/kg) was administrated once a day for 7 days before cerebral ischemia onset.

RESULTS:

We found that combined rosuvastatin and resveratrol pretreatment not only significantly decreased the neurologic defective score, cerebral infarct volume, the levels of caspase-3, and Interleukin-1β (IL-1β) but also significantly increased the ratios of Bcl-2/Bax and LC3II/LC3I, as well as the level of Becline-1, compared with resveratrol alone or rosuvastatin alone pretreatment group. Rosuvastatin alone pretreatment significantly increased the ratio of LC3II/LC3I and the level of Beclin-1. However, there were no significant differences in the neurologic defective score, cerebral infarct volume, the levels of caspase-3, IL-1β, and Beclin-1, and the ratios of Bcl-2/Bax and LC3II/LC3I between resveratrol pretreatment group and rosuvastatin pretreatment group.

CONCLUSIONS:

Synergistically enhanced antiapoptosis, anti-inflammation, and autophagy activation might be responsible for the synergistic neuroprotective effects of combining rosuvastatin with resveratrol on cerebral ischemia/reperfusion injury.

• Authors: Ying Liu, HongNa Yang, GuoYong Jia, Lan Li, Hui Chen, JianZhong Bi, CuiLan Wang
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 27 Issue 6 Pg. 1697-1704 (Jun 2018) ISSN: 1532-8511 [Electronic] United States
• PMID: 29525080 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Apoptosis Regulatory Proteins
• Autophagy-Related Proteins
• Inflammation Mediators
• Neuroprotective Agents
• Stilbenes
• Rosuvastatin Calcium
• Resveratrol

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Autophagy (drug effects)
• Autophagy-Related Proteins (metabolism)
• Brain (drug effects, metabolism, pathology)
• Cytoprotection
• Disease Models, Animal
• Drug Synergism
• Drug Therapy, Combination
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, pathology)
• Inflammation Mediators (metabolism)
• Male
• Neuroprotective Agents (pharmacology)
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology, prevention & control)
• Resveratrol
• Rosuvastatin Calcium (pharmacology)
• Signal Transduction (drug effects)
• Stilbenes (pharmacology)