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《中国药理学报：英文版》
>Xyloketal B alleviates cerebral infarction and neurologic deficits in a mouse stroke model by suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway
Xyloketal B alleviates cerebral infarction and neurologic deficits in a mouse stroke model by suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway
Xyloketal B (Xyl-B) is a novel marine compound isolated from mangrove fungus Xylaria sp.We previously demonstrated that pretreatment with Xyl-B exerted neuroprotective effects and attenuated hypoxic-ischemic brain injury in neonatal mice.In the present study we investigated the neuroprotective effects of pre-and post-treatment with Xyl-B in adult mice using a transient middle cerebral artery occlusion (tMCAO) model,and explored the underlying mechanisms.Adult male C57 mice were subjected to tMCAO surgery.For the pre-treatment,Xyl-B was given via multiple injections (12.5,25,and 50 mg·kg-1·d-1,ip) 48 h,24 h and 30 min before ischemia.For the post-treatment,a single dose of Xyl-B (50 mg/kg,ip) was injected at 0,1 or 2 h after the onset of ischemia.The regional cerebral perfusion was monitored using a laser-Doppler flowmeter.TYC staining was performed to determine the brain infarction volume.We found that both pre-treatment with Xyl-B (50 mg/kg) and post-treatment with Xyl-B (50 mg/kg) significantly reduced the infarct volume,but had no significant hemodynamic effects.Treatment with Xyl-B also significantly alleviated the neurological deficits in tMCAO mice.Furthermore,treatment with Xyl-B significantly attenuated ROS overproduction in brain tissues;increased the MnSOD protein levels,suppressed TLR4,NF-κB and iNOS protein levels;and downregulated the mRNA levels of proinflammatory cytokines,including IL-1β,TNF-α,IL-6 and IFN-y.Moreover,Xyl-B also protected blood-brain barrier integrity in tMCAO mice.In conclusion,Xyl-B administered within 2 h after the onset of stroke effectively protects against focal cerebral ischemia;the underlying mechanism may be related to suppressing the ROS/TLR4/NF-κB inflammatory signaling pathway.
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