Garcinol protects against cerebral ischemia-reperfusion injury in vivo and in vitro by inhibiting inflammation and oxidative stress.

Abstract

Garcinol, a polyisoprenylated benzophenone derivative, is isolated from fruit rind of Garcinia indica. It is known to exert potent anti-inflammatory and anti-oxidative properties. In the present study, we tried to investigate the neuroprotective effects of garcinol on a rat model with middle cerebral artery occlusion/reperfusion (MCAO/R) and a cell model subjected to oxygen glucose deprivation and reperfusion (OGD/R). In vivo, we found that the rats with garcinol treatment showed a lower neurological deficit score and a smaller infarct size compared with the rats with ischemia-reperfusion (I/R) injury alone. We further found that garcinol treatment decreased cerebral I/R-induced inflammatory cytokines and oxidative stress, including inhibiting the production of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), decreasing the levels of malonaldehyde (MDA) and nitric oxide (NO), and suppressing the decreased superoxide dismutase (SOD) activity. Moreover, the suppression of toll-like receptor (TLR) 4 and nuclear NF-κB (p65) expression by garcinol was found both in vivo and in vitro. In addition, NF-κB activator or TLR4 overexpression was employed to investigate its involvement in the effects of garcinol. The results showed that NF-κB activator or TLR4 overexpression at least in part reversed the anti-inflammatory and anti-oxidative properties of garcinol in vitro. Taken together, the data suggest that garcinol could protect against cerebral I/R injury through attenuating inflammation and oxidative stress, and improving neurological function. The molecular mechanism might be related to its suppression of TLR4/NF-ĸB signal pathway.

• Authors: Yingchao Kang, Yaping Sun, Tiantian Li, Zelin Ren
• Journal: Molecular and cellular probes (Mol Cell Probes) Vol. 54 Pg. 101672 (12 2020) ISSN: 1096-1194 [Electronic] England
• PMID: 33186709 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Cytokines
• Inflammation Mediators
• NF-kappa B
• Neuroprotective Agents
• Terpenes
• Glucose
• Oxygen
• garcinol

Topics

• Animals
• Cytokines (metabolism)
• Glucose (deficiency)
• Inflammation (complications, pathology)
• Inflammation Mediators (metabolism)
• Male
• NF-kappa B (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Oxygen
• PC12 Cells
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (complications, drug therapy, physiopathology)
• Signal Transduction (drug effects)
• Terpenes (pharmacology, therapeutic use)