Umbelliferone ameliorates cerebral ischemia-reperfusion injury via upregulating the PPAR gamma expression and suppressing TXNIP/NLRP3 inflammasome.

Abstract

Umbelliferone (UMB), a natural antioxidant belonging to coumarin derivatives, is able to cross the blood-brain barrier and protect neuronal cells from death. Here we aimed to investigate the effects of UMB in a rat model of focal cerebral ischemia induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Pretreatment with UMB (15 and 30 mg/kg) for 7 consecutive days ameliorated the neurological outcomes, infarct volume and brain edema in brains of MCAO rats. Our results provided evidence that UMB significantly protected neuronal cells against cerebral ischemia reperfusion-induced injury. Furthermore, UMB treatment could inhibited the level of oxidative stress and the production of inflammatory cytokines in brain tissues of MCAO rats. In addition, UMB significantly upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), which exhibited neuroprotective effects in neurodegenerative disease. UMB treatment also suppressed NLRP3 inflammasome activation via reducing expression of Thiredoxin-interactive protein (TXNIP). These results suggest that UMB may have beneficial effects for neuroprotection against focal cerebral ischemic partly through the inhibition of TXNIP/NLRP3 inflammasome and activation of PPAR-γ.

• Authors: Xiangxiang Wang, Ruipeng Li, Xuan Wang, Qiang Fu, Shiping Ma
• Journal: Neuroscience letters (Neurosci Lett) Vol. 600 Pg. 182-7 (Jul 23 2015) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 26071904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antioxidants
• Carrier Proteins
• Cell Cycle Proteins
• Inflammasomes
• Interleukin-18
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuroprotective Agents
• Nlrp3 protein, rat
• PPAR gamma
• TXNIP protein, rat
• Umbelliferones
• Malondialdehyde
• 7-hydroxycoumarin
• Superoxide Dismutase

Topics

• Animals
• Antioxidants (pharmacology, therapeutic use)
• Brain Edema (drug therapy)
• Brain Infarction (drug therapy, pathology)
• Brain Ischemia (drug therapy, metabolism, pathology)
• Carrier Proteins (biosynthesis, metabolism)
• Cell Cycle Proteins
• Gene Expression Regulation
• Inflammasomes (metabolism)
• Interleukin-18 (metabolism)
• Interleukin-1beta (metabolism)
• Male
• Malondialdehyde (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuroprotective Agents (pharmacology, therapeutic use)
• PPAR gamma (metabolism)
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, metabolism, pathology)
• Superoxide Dismutase (metabolism)
• Umbelliferones (pharmacology, therapeutic use)