Neuroprotective effects of Danggui-Jakyak-San on rat stroke model through antioxidant/antiapoptotic pathway

Ethnopharmacological relevanceDangui-Jakyak-San (DJ) is a traditional Korean medicinal polyherb, prescribed typically in patients with insufficient blood supply in Eastern Asia. The DJ also has been reported to have neuroprotective effects in vitro and in vivo studies.Aim of studyThe therapeutic potential of DJ was examined in stroke rat model, in comparison with donepezil, a reversible acetylcholinesterase inhibitor.Materials and methodsIschemic stroke rat model was induced by surgery of permanent occlusion of middle cerebral artery (pMCAO). The model was orally administered with distilled water (pMCAO control), donepezil at 10 mg/kg (Donepezil) and DJ at 200, 100 and 50 mg/kg (DJ 200, DJ 100 and DJ 50, respectively). Sham had the same surgery excepting for the pMCAO, and it was administered with distilled water (sham control).ResultsAfter the administration for 28 days, the groups of DJ exhibited dose-dependent reduction in infarct/defect volumes with improvement in sensorimotor and cognitive motor function, comparing to pMCAO control. The DJ treatments seemed to enhance antiapoptotic and antioxidant effects; increases in antiapoptotic expressions (STAT3 and Pim-1) and decreases in lipid peroxidation (MDA) together with increases in contents of endogenous antioxidant (GSH) and activities of antioxidant enzymes (catalase and SOD). The histopathological analyses revealed significant reduction in neuronal apoptosis (caspase-3 and PARP) and neuronal degradation with atrophy and degeneration, in the DJ treatments. Furthermore, the oxidative stresses (nitrotyrosine as an iNOS factor and 4-HNE as a marker of lipid peroxidation) were observed mild. Although the similar neuroprotective effects were observed, the body weight loss was scarcely alleviated in Donepezil comparing to pMCAO control.ConclusionThese suggest that DJ ameliorate the neurological dysfunction of cerebral ischemia through augmentation of antioxidant defense system and up-regulation of STAT3 and Pim-1.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (351 K)Download as PowerPoint slide