Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on ischemic and hypoxic neuronal injury

Abstract

BackgroundStroke is one of the leading causes of neuronal death. Sesamin is known for neuroprotection by its antioxidant and anti-inflammatory properties but it lacks blood–brain barrier (BBB) activity. A panel of sesamin derivatives was screened and 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) was selected for high BBB activity and tested for its neuroprotective effect.MethodsThe focal cerebral ischemia of Sprague–Dawley rats and hypoxia models of murine BV-2 microglia or PC12 cells under oxygen/glucose deprivation were used for in vivo and in vitro test, respectively. Lipid peroxidation and superoxide dismutase (SOD) activity from the ischemic brain were tested and reactive oxygen species (ROS), cytokine production, prostaglandin (PGE2) and related signaling pathways from hypoxic cells were examined by ELISA or Western blot assay, respectively.ResultsBBD showed a protective effect when given 90 min after the focal cerebral ischemia. It also reduced lipid peroxidation and preserved SOD activity from the ischemic brain. The mechanism of BBD was further confirmed by attenuating ROS, cytokine production, and PGE2 release from hypoxic BV-2 or PC12 cells. BBD significantly reduced hypoxia-induced c-Jun N-terminal kinases (JNK) and modulated AKT-1 and caspase-3 (survival and apoptotic pathways) in BV-2 cells, and inhibited hypoxia-induced JNK and cyclooxygenase-2 activation in PC12 cells.ConclusionsThe neuroprotective effect of BBD on ischemia/hypoxia models was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of ischemia/hypoxia injury.

Protective effect of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride on hypoxia-induced toxicity by suppressing microglial activation in BV-2 cells

“…BV-2 cells were pretreated with KHG26792 for 30 min followed by hypoxia for 24 h. The results of this assay demonstrated a 49% reduction in cell viability 24 h after hypoxia ( Fig. 1A ), which is in agreement with previous observations ( 2 , 10 ). However, 50 μM KHG26792 rescued cells from hypoxia-induced toxicity to near normal viability levels ( Fig.…”

“…Previous studies have reported that hypoxia–ischemia-induced apoptosis in the brain is evident by the activation of caspase-3 ( 10 ). We further examined the effects of KHG26792 on the levels of caspase-3 as hypoxia is known to promote cell death through a caspase-3 dependent pathway ( 11 ).…”

In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists

“…It is well known that a good neurotherapeutic drug should be able to pass the blood-brain barrier (BBB) to reach the brain target site [45]. Many studies have showed that lignans containing typical aromatic rings can cross the BBB [46].…”

“…Combining the results of bioinformatics analysis and in vivo studies, we assumed that lignans in KL played roles as the main ligands of the 5-HT1AR. It is well known that a good neurotherapeutic drug should be able to pass the blood-brain barrier (BBB) to reach the brain target site [ 45 ]. Many studies have showed that lignans containing typical aromatic rings can cross the BBB [ 46 ].…”

Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy

“…Although many adverse outcomes occur once the BBB is permeable, there are experimental studies that show that stabilizing the BBB and reducing inflammatory markers after hypoxic ischemic events as well as HIE may be beneficial [ 36 , 37 , 38 , 39 , 40 ]. For example, a study exploring the mechanisms of granulocyte-colony stimulating factor (G-CSF) as a treatment after a neonatal rat model of HIE, demonstrated that G-CSF elicited BBB stabilization by G-CSF receptor stimulation and activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway.…”