Aqueous extract of Terminalia arjuna bark attenuates blood brain barrier disruption in rat model of transient focal cerebral ischemia

Terminalia arjuna (TA) is a widely used medicinal plant in Indian traditional medicinal system. In the Ayurvedic system of medicine it is used as a cardiotonic and also well documented in experimental studies for its efficacy in various cardiac ailments. Few recent studies have reported its neuroprotective effects in rat model of cerebral ischemia. However, the effect of TA on cerebral ischemia induced Blood brain barrier (BBB) damage is still unclear. The present study is aimed to evaluate the ameliorative effect of aqueous extract of Terminalia arjuna (aeTA) against transient focal cerebral ischemia induced BBB damage. Adult male Sprague-dawley rats (270–300g) were randomly divided into three groups: Sham, Lesion (Middle cerebral artery occlusion for 2 hours) and aeTA pre-treatment at a dose of 500 mg /kg body weight/day orally for 15 days prior to MCAo. After 24 h of ischemic-reperfusion injury, the rats were assessed for behavioral deficits by Modified neurological severity scoring (mNSS), infarct measurement by Triphenyl tetrazolium chloride (TTC) staining, BBB integrity by Evans blue (EB) staining, protein and mRNA expressions of TJ proteins (Claudin5 & Occludin), MMPs (MMP2 & MMP9) and TIMPs (TIMP1 & TIMP2) through western blot analysis and real time PCR. The pre-treatment with aeTA for 15 days exhibited significant improvement in neurological outcome and reduced infarct volume compared with the MCAo rats. The aeTA treatment also reduced the BBB damage which was confirmed through decreased EB extravasations, significant reduction in protein levels of MMPs (MMP2 &MMP9) and maintaining the protein levels of tight junction proteins. We also found that aeTA treatment downregulated the mRNA levels of MMPs and upregulated mRNA expression levels of TIMPs and tight junction proteins (Claudin5 & Occludin). These results demonstrate the neuroprotective property of aeTA treatment by reducing the MMPs mediated BBB damage after focal cerebral ischemia.