Astilbin protects against cerebral ischaemia/reperfusion injury by inhibiting cellular apoptosis and ROS-NLRP3 inflammasome axis activation.

Abstract

BACKGROUND:

Ischaemic stroke is a lethal cerebrovascular disease that occurs worldwide. Astilbin is a natural flavonoid compound with various physiological activities. The purpose of this study was to investigate the neuroprotective effects of Astilbin after cerebral ischaemia reperfusion (I/R) injury.

METHODS:

The oxygen and glucose deprivation (OGD) model was used to simulate cerebral I/R injury in vitro. Cell viability was measured via CCK-8 and LDH release assays. Cell apoptosis was measured via Hoechst 33258 staining and flow cytometry assays. ROS was detected via flow cytometry assay. The protein expression levels were determined by western blotting. The middle cerebral artery occlusion (MCAO) model was used to simulate cerebral I/R injury in vivo. Cerebral ischaemic volume was measured by TTC staining. The Zea-Longa score, rota-rod test, and foot-fault test were used to evaluate behavioural changes and neurological deficits in rats.

RESULTS:

Astilbin significantly enhanced cell viability and decreased LDH release after OGD treatment in vitro. Astilbin effectively curbed cell apoptosis induced by OGD via inhibiting the activation of caspase-3, decreasing the ratio of Bax/Bcl-2 and decreasing FADD. Astilbin also inhibited OGD-induced inflammation by suppressing ROS-NLRP3 inflammasome axis activation. Further results revealed that Astilbin could suppress the MAPK pathway and activate the PI3K/AKT pathway. Finally, Astilbin significantly reduced the cerebral infarction volume and relieved neurological deficits in rats in vivo.

CONCLUSION:

Astilbin could defend against cerebral I/R injury by inhibiting apoptosis and inflammation via suppressing the MAPK pathway and activating the AKT pathway.

• Authors: Yu Li, Rong Wang, Lian Xue, Yilin Yang, Feng Zhi
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 84 Pg. 106571 (Jul 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32413740 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Flavonols
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuroprotective Agents
• Nlrp3 protein, rat
• Reactive Oxygen Species
• astilbin
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Flavonols (pharmacology, therapeutic use)
• Infarction, Middle Cerebral Artery (drug therapy, immunology, metabolism)
• Inflammasomes (metabolism)
• Male
• Mitogen-Activated Protein Kinases (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• PC12 Cells
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (drug therapy, immunology, metabolism)