Abstract

An active component has been isolated by reverse-phase high performance liquid chromatography (HPLC) from Achyranthes bidentata Blume polypeptides that are extracted from Achyranthes bidentata Blume, a Chinese medicinal herb. The active component is called ABPPk based on the order of HPLC elution. In this study, we used in vitro and in vivo experimental models of cerebral ischemia to investigate the possible neuroprotective effect of ABPPk. ABPPk treatment promoted neuronal survival and inhibited neuronal apoptosis in primary cortical neurons exposed to oxygen and glucose deprivation and in rats subjected to transient middle cerebral artery occlusion. The role of ABPPk in protection against ischemia-induced neuronal damage might be mediated by mitochondrial-dependent pathways, including modulation of apoptosis-related gene expression, regulation of mitochondrial dysfunction through restoring mitochondrial membrane potential, reducing release of mitochondrial apoptogenic factors, and inhibiting intracellular ROS production. The neuroprotective effect of ABPPk may suggest the possible use of this agent in the treatment and prevention of cerebral ischemic stroke.

Highlights

  • Cerebral ischemic stroke is a major cause of death and disability worldwide

  • We found that ABPPk inhibited neuronal insult in primary cortical neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to middle cerebral artery occlusion (MCAO)-induced brain ischemia

  • ABPPk itself caused no deleterious effects on primary cortical neurons, which may be taken as a prerequisite for examining the protective effect of ABPPk

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Summary

Introduction

Cerebral ischemic stroke is a major cause of death and disability worldwide This neurological disease is caused by an obstruction of blood flow to the brain, which triggers the onset of ischemic cascades, including energy failure, excitotoxicity, oxidative stress, inflammation, and apoptosis. The aqueous extract of Achyranthes bidentata Blume has been shown to promote peripheral nerve regeneration in rabbits with crush injury to the common peroneal nerve [2]. From the aqueous extract of Achyranthes bidentata Blume, we isolated Achyranthes bidentata polypeptides (ABPP), which attenuated the glutamate-induced apoptosis in primary hippocampal neurons, supported recovery from experimental cerebral ischemia in vivo [3,4,5], and promoted peripheral nerve regeneration in rodents with sciatic nerve crush through stimulating release of growth factors [6,7]. We used reverse phase HPLC to separate several active components from ABPP, and one of these components, called ABPPk according to the elution order on C18 reverse phase column, showed the best neuroactivity among all components

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