Phenolic alkaloids from Menispermum dauricum reduce inflammatory reaction and ischemic brain damage in cerebral ischemia rats

Abstract

Stroke is a debilitating disease for which limited therapeutic approaches are available currently. Thus, there is an urgent need for developing novel therapies for stroke. Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Phenolic alkaloids from Menispermum dauricum (PAMD) have gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigated the potential neuroprotective role of PAMD and the underlying mechanisms. Cerebral ischemia in male Sprague–Dawley rats was induced by middle cerebral artery occlusion (MCAO) and PAMD was pre-administered intragastrically once daily for five consecutive days before surgery. The effect of the PAMD on the ethology and pathomorphology of the rats with MCAO were observed before and after treatment. Neurological deficit scores and morphological characteristic were measured after cerebral ischemia. The expression of intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2) in ischemic rat brain was determined by immunohistochemistry at 24, 48, and 72 h after cerebral ischemia. Compared with MCAO groups, PAMD noticeably improved neurological deficit at 24, 48, and 72 h after ischemic insult. Consistent with these results, our data also indicated that PAMD significantly downregulated the expression of ICAM-1 and COX-2 (P < 0.05). The results provided a neuroprotective effect of PAMD in cerebral ischemia and this effect was exerted by downregulating the expression of ICAM-1and COX-2. Our results demonstrated that PAMD reduced inflammatory reaction and brain damage in cerebral ischemia in rats. PAMD exerts neuroprotection against ischemic brain damage, which might be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory genes.