Levo-tetrahydropalmatine Attenuates Neuron Apoptosis Induced by Cerebral Ischemia-Reperfusion Injury: Involvement of c-Abl Activation.

Abstract

Ischemic stroke is one of the most dangerous acute diseases which causes death or deformity. Apoptosis has been shown to play an important role in the development and pathogenesis of cerebral ischemia-reperfusion injury (I/R injury), but the related mechanism is unclear. Levo-tetrahydropalmatine (L-THP), a bioactive ingredient extracted from the Chinese herb Corydalis, can penetrate the blood-brain barrier and exert various pharmacological effects on neural tissues. The present study examined the neuroprotective effect of L-THP on neuronal apoptosis induced by cerebral I/R injury. Results showed that pretreatment with L-THP (12.5, 25, and 50 mg/kg) improved neurological outcomes and reduced infarct volume and cerebral edema in comparison with the brains of the middle cerebral artery occlusion (MCAO) group. These findings provided evidence for the neuroprotective effects of L-THP against cerebral I/R injury. Furthermore, administration of L-THP enhanced the expression of Bcl-2 and attenuated the content of Bax, cleaved caspase-3, and PARP. L-THP could improve the reduction of NeuN-positive cells induced by I/R injury. These results suggested that L-THP could inhibit neuroapoptosis in cerebral ischemic rats. c-Abl was discovered as the critical protein responsible for neurocyte apoptosis; however, few data have been published on the relation between ischemic stroke and the expression of c-Abl. We found that both c-Abl expression and neuronal apoptosis were significantly increased in the MCAO group, while pretreatment with L-THP could ameliorate this effect. Therefore, we deduced that reduced c-Abl overexpression may play a role in the anti-apoptosis effect of L-THP after cerebral I/R injury. Thus, L-THP may provide a potential therapeutic approach for the treatment of ischemic stroke. Graphical Abstract ᅟ.

• Authors: Ruoxi Sun, Yichen Song, Shanshan Li, Zhanqiang Ma, Xueyang Deng, Qiang Fu, Rong Qu, Shiping Ma
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 65 Issue 3 Pg. 391-399 (Jul 2018) ISSN: 1559-1166 [Electronic] United States
• PMID: 29974381 (Publication Type: Journal Article)

Chemical References

• Berberine Alkaloids
• Neuroprotective Agents
• tetrahydropalmatine
• Proto-Oncogene Proteins c-abl

Topics

• Animals
• Apoptosis
• Berberine Alkaloids (therapeutic use)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism)
• Male
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (therapeutic use)
• Proto-Oncogene Proteins c-abl (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley