nsc-4347 and Infarction--Middle-Cerebral-Artery

Piper nigrum L. and P. longum L. are widely used in various medicinal formulations. The dichloromethane fraction of Piper nigrum L. and P. longum L. (DF) can prevent cerebral ischemic injury although the underlying mechanisms are obscure. The aim of this study was to evaluate the potential neuroprotective effects of DF on a rat model of permanent middle cerebral artery occlusion (pMCAO) and assess the molecular mechanisms. Animals were administered with DF (50, 100, and 150 mg/kg) or nimodipine (12 mg/kg) 6 h after pMCAO for 14 consecutive days via intragastric gavage. In the vitro this study identified that DF reduced neurological severity scores and improved survival rate. Results showed that DF markedly inhibited the percentage of apoptotic cells as well as neuronal autophagy and mitigated the overall neuronal and vascular damage in the ischemic region. Western blot testing showed that at the molecular level, DF significantly suppressed ischemia-induced activated expression of LC3, Beclin1, Atg12, and Atg5. Overall, our study indicated that DF attenuated neuronal autophagy by suppressing the expression of autophagy-related proteins to generate neuroprotection effect for ischemic stroke.

Topics: Animals; Autophagy-Related Proteins; Brain Injuries; Brain Ischemia; Infarction, Middle Cerebral Artery; Ischemic Stroke; Methylene Chloride; Neuroprotective Agents; Piper; Piper nigrum; Rats; Stroke

Piper nigrum L. and Piper longum L. consist a classic formula in traditional Chinese Hui medicine and are widely used in treatment of stroke. To examine the therapeutic effect of neuron injury after apoplexy, we used a permanent middle cerebral artery occlusion model in rats to investigate the effects of dichloromethane fraction (DF) of Piper nigrum L. and Piper longum L.. DF alleviated neurological deficits and markedly prevented ischemia-induced cellular damage. Immunohistochemical micrographs revealed that PSD-95 and syn-I proteins increased, and α-syn presented reduced expression in brain samples from the sham group. Western blot analyses revealed that the model group exhibited a noticeable reduction in PSD-95, p-CaMK II, CaM, and NR2B. The DF-treated model group exhibited increased PSD-95, p-CaMK II, CaM, and NR2B. UPLC-Q-TOF/MS analysis revealed eight main components of DF, of which piperine accounted for the largest proportion.

Topics: alpha-Synuclein; Animals; Behavior, Animal; Brain; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calmodulin; Disease Models, Animal; Disks Large Homolog 4 Protein; Infarction, Middle Cerebral Artery; Male; Methylene Chloride; Motor Activity; Neurons; Neuroprotective Agents; Phosphorylation; Piper; Piper nigrum; Plant Extracts; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Solvents; Synapsins