Root of Angelica gigas Nakai ameliorates ischemic stroke-induced brain injury in mice through the activation of the PI3K/AKT/mTOR and MAPK pathways
Abstract Background: Ischemic stroke results in disability and increased risk of morbidity, resulting in a massive burden on patients and caregivers. Recombinant tissue plasminogen activator (r-tPA) has a limited window of opportunity for efficacy and causes side effects including hemorrhage; therefore, safer and more effective therapeutic strategies are required. In this study, the neuroprotective effects of a methanolic extract of AGR (AGmex) in ischemia/reperfusion-induced brain injury in mice were investigated. Methods: Ischemic brain injury was induced in the mice by transient occlusion of the middle cerebral artery (tMCAO) for 120 min, and the effect of AGmex on the amount of infarction was measured. Cresyl violet and hematoxylin and eosin stains were used to identify changes in the neurons, nuclei, and cytoplasm. Western blotting, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining were used to elucidate the neuroprotective mechanism of AGmex. Results: AGmex effectively reduced the infarction volume when the mice were pre-treated at 1,000 mg/kg bw/day for two consecutive days (AGmex 1000 group). Neurons, nuclei, and cytoplasmic staining were the lowest in the MCAO group, but recovered in the AGmex 1000 group. In addition, proteins related to cell growth, differentiation, and death were up-regulated in the AGmex 1000 group. Conclusion: The major recovery mechanisms appeared to be attenuation of the mitochondrial function of Bcl-2/Bax, and activation of the PI3K/AKT/mTOR and MAPK signaling pathways in ischemic neurons.