Berberis vulgaris/Picrorhiza kurroa: Extending the Treatment Window for Reperfusion Injury

Abstract

Aims: The present study investigates the neuroprotective effects of Berberis vulgaris and Picrorhiza kurroa in a rodent model of cerebral ischemia – reperfusion.    Study Design: Rats were pretreated with Berberis vulgaris, Picrorhiza kurroa or vehicle 30 minutes prior to cerebral ischemia and reperfusion injury. Post-mortem infarct measurements of the cerebral cortex were used to assess neuroprotection for each treatment.  Place and Duration of Study: The study took place in the Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island between July 2014 and January 2015.  Methodology: The right middle cerebral artery (MCA) was occluded for 30 minutes followed by 5.5 hours of reperfusion in anaesthetized male Sprague-Dawley rats (250-350 g). Berberis vulgaris (0.001-0.1 mg/kg) and Picrorhiza kurroa (0.0001-1.0 mg/kg) were administered singly and in combination (0.001 mg/kg each) 30 minutes prior to MCA occlusion as well as at several intervals during the reperfusion period. Infarct volume in the affected hemisphere was measured to assess neuroprotection. Results: Occlusion of the right MCA for 30 minutes followed by 5.5 hours of reperfusion in anaesthetized male Sprague-Dawley rats produced a focal ischemic lesion localized to the prefrontal cortex. Intravenous administration of either Berberis vulgaris or Picrorhiza kurroa 30 minutes prior to MCA occlusion provided significant neuroprotection following ischemia-reperfusion.  Furthermore, Berberis vulgaris (0.1 mg/kg, i.v.) or Picrorhiza kurroa (1.0 mg/kg, i.v.) could be administered during the ischemic period itself, as well as up to 90 minutes into the reperfusion period to provide neuroprotection. A combined injection of Berberis vulgaris with Picrorhiza kurroa using subthreshold doses of each (0.001 mg/kg) reduced infarct volume in the ischemic cortex when injected 30 minutes before MCA occlusion, 15  minutes into the ischemic period or up to 150 minutes following reperfusion. While Berberis vulgaris and Picrorhiza kurroa co-administration significantly reduced both baseline mean arterial pressure and heart rate in non-ischemic animals, suggestive of a central effect on autonomic tone, no significant effect was observed on baroreflex sensitivity in rats undergoing ischemia-reperfusion Conclusion: Natural products such as Berberis vulgaris and Picrorhiza kurroa may hold the key to reducing morbidity and mortality associated with post-stroke complications due to reperfusion injury.