Effect of magnolol on cerebral injury and blood brain barrier dysfunction induced by ischemia-reperfusion in vivo and in vitro

Abstract

Magnolol, a neolignan compound isolated from traditional Chinese medicine Magnolia officinalis, has a potentially therapeutic influence on ischemic stroke. Previous studies have demonstrated that cerebral ischemia-reperfusion (I-R) and blood-brain barrier (BBB) are involved in the pathogeneses of stroke. Therefore, in vivo and in vitro studies were designed to investigate the effects of magnolol on I-R-induced neural injury and BBB dysfunction. In cerebral I-R model of mice, cerebral infarct volumes, brain water content, and the exudation of Evans blue were significantly reduced by intravenous injection with magnolol at the doses of 1.4, 7.0, and 35.0 μg/kg. When primary cultured microglial cells were treated with 1 μg/ml lipopolysaccharide (LPS) plus increasing concentrations of magnolol, ranging from 0.01 to 10 μmol/L, magnolol could statistically inhibit LPS-induced NO release, TNF-α secretion, and expression of p65 subunit of NF-κB in the nucleus of microglial cells. In the media of brain microvascular endothelial cells (BMECs), oxygen and glucose deprivation-reperfusion (OGD-R) could remarkably lead to the elevation of TNF-α and IL-1β levels, while magnolol evidently reversed these effects. In BBB model in vitro, magnolol dose- and time-dependently declined BBB hyperpermeability induced by oxygen and glucose deprivation (OGD), OGD-R, and ephrin-A1 treatment. More importantly, magnolol could obviously inhibit phosphorylation of EphA2 (p-EphA2) not only in ephrin-A1-treated BMECs but also in cerebral I-R model of mice. In contrast to p-EphA2, magnolol significantly increased ZO-1 and occludin levels in BMECs subjected to OGD. Taken together, magnolol can protect neural damage from cerebral ischemia- and OGD-reperfusion, which may be associated with suppressing cerebral inflammation and improving BBB function.

LPS Pretreatment Attenuates Cerebral Ischaemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis

“…In cerebral IRI, many studies support the view that LPS aggravates cerebral IRI [38-42]. There are also reports of the neuroprotective effects of LPS pretreatment on cerebral IRI.…”

CYP3A Excipient-Based Microemulsion Prolongs the Effect of Magnolol on Ischemia Stroke Rats

“…Magnolol exhibited strong radical scavenging, antioxidant, and anti-inflammatory activity that could significantly reduce the accumulation of superoxide anions, oxidative damage, apoptosis, and autophagy in the ischemic brain [38][39][40]. In this study, we developed a CYP3A-excipient ME, which was designed to be administrated intraperitoneally to increase the solubility and bioavailability of magnolol and increase its neuroprotective effect against ischemic brain injury.…”

“…This may be attributed to the primary MCAO damage that led to the death of dopaminergic neurons in substantia nigra [41,42]. Magnolol played a role in the antioxidant and anti-inflammation effects, for example, during the second reperfusion damage period [38,39]. There were no shreds of evidence that magnolol can enhance the regeneration of dopaminergic neurons in the brain motor area.…”

Magnolol Ameliorates Behavioral Impairments and Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

“…Moreover, MN has been demonstrated to ameliorate learning and memory impairments by preserving cholinergic function in the forebrain of the SAMP8 mice [17]. Importantly, MN could cross the blood-brain barrier (BBB) and remain relatively stable in the brain after oral administration [21]. Moreover, no troublesome side effects have been reported so far in humans after ingestion of MN [13].…”