9-Methylfascaplysin exerts anti-ischemic stroke neuroprotective effects via the inhibition of neuroinflammation and oxidative stress in rats.

Abstract

OBJECTIVES:

This study was aimed to investigate the neuroprotective effects of 9-methylfascaplysin, a novel marine derivative derived from sponge, against middle cerebral artery occlusion/reperfusion (MCAO)-induced motor impairments, neuroinflammation and oxidative stress in rats.

METHODS:

Neurological and behavioral tests were used to evaluate behavioral changes. The 2, 3, 5-triphenyltetrazolium chloride staining was used to determine infarct size and edema extent. Activated microglia/macrophage was analyzed by immunohistochemical staining of Iba-1. RT-PCR and ELISA were used to measure the expression of inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, CD16 and CD206. Western blotting analysis was performed to explore the activation of nuclear factor-κB (NF-κB) and NLRP3. The levels of oxidative stress were studied by evaluating the activities of superoxide dismutase, catalase and glutathione peroxidase.

RESULTS:

Post-occlusion intracerebroventricular injection of 9-methylfascaplysin significantly attenuated motor impairments and infarct size in MCAO rats. Moreover, 9-methylfascaplysin reduced the activation of microglia/macrophage in ischemic penumbra as evidenced by the decreased Iba-1-positive area and the reduced expression of pro-inflammatory factors. Furthermore, 9-methylfascaplysin inhibited MCAO-induced oxidative stress and activation of NF-κB and NLRP3 inflammasome.

CONCLUSION:

All the results suggested that 9-methylfascaplysin might produce neuroprotective effects against MCAO via the reduction of oxidative stress and neuroinflammation, simultaneously, possibly via the inhibition of NF-κB and NLRP3 inflammasome.

• Authors: Difan Zhang, Yi Feng, Hanbo Pan, Zhenquan Xuan, Sicheng Yan, Yuechun Mao, Xiao Xiao, Xinghan Huang, Hui Zhang, Fei Zhou, Bojun Chen, Xiaowei Chen, Hao Liu, Xiaojun Yan, Hongze Liang, Wei Cui
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 97 Pg. 107656 (Aug 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 33895476 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• 9-methylfascaplysin
• Indoles
• Inflammasomes
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neuroprotective Agents
• Nlrp3 protein, rat

Topics

• Animals
• Disease Models, Animal
• Humans
• Indoles (pharmacology, therapeutic use)
• Infarction, Middle Cerebral Artery (drug therapy, immunology, pathology)
• Inflammasomes (antagonists & inhibitors, metabolism)
• Male
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors, metabolism)
• Neuroinflammatory Diseases (drug therapy, immunology, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress (drug effects, immunology)
• Rats
• Signal Transduction (drug effects, immunology)