nsc-4347 and Ischemic-Stroke

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

Dichloromethane fraction (DF) of Piper nigrum L. and P. longum L. (PnL and PlL), has been found to exert a protective effect against ischemic stroke in rats. However, the regulatory mechanism exerted by PnL and PIL have not been fully elucidated. In this study, we found that DF greatly ameliorated cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion (pMCAO). The neurological score, behavioral assessment, brain infarct volume, phosphorylation of AKT (p-AKT), phosphorylation mTOR (p-mTOR), and Atg7 protein levels were determined. Additionally, we discovered that DF pretreatment reduced infarct volume, neurological score, and brain damage. Furthermore, DF therapy caused the downregulation of Atg7 and p-AKT expression, as well as the upregulation of p-mTOR expression. In conclusion, our findings indicated that DF treatment can reduce brain damage and inhibit apoptosis and autophagy by activating the Akt-mTOR signaling pathway in ischemic stroke.

Topics: Animals; Autophagy; Cerebral Cortex; Ischemic Stroke; Male; Methylene Chloride; Motor Skills; Neuroprotective Agents; Piper; Piper nigrum; Plant Extracts; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; TOR Serine-Threonine Kinases