Ligustrazine suppresses neuron apoptosis via the Bax/Bcl‐2 and caspase‐3 pathway in PC12 cells and in rats with vascular dementia

Abstract

The aim of this study was to examine the comprehensive neuroprotective mechanism of ligustrazine, which is extracted from Ligusticum Chuanxiong Hort., against vascular dementia (VD) in rats and apoptosis in oxygen and glucose deprivation (OGD) PC12 cells. Rats were subjected to bilateral common carotid artery occlusion (BCCAO) surgery and administered ligustrazine intragastrically for 6 weeks. At the end of the experiments, the hippocampal biomarkers brain-derived neurotrophic factor (BDNF), monocyte chemotactic protein 1 (MCP-1), and homocysteine (Hcy) were examined. In experiments in vitro, OGD PC12 cells were treated with ligustrazine for 0.5, 1, 3, 6, 12, or 24 h. The cell-released biomarkers BDNF, MCP-1, and Hcy were examined. Microscopy, acridine orange-ethidium bromide (AO/ EB) staining, and flow cytometry assays were performed to investigate apoptosis. Cleaved caspase-3, Bcl-2 associated X protein (Bax), and B cell lymphoma 2 (Bcl-2) expression was examined using Western blot assays. The results showed that biomarkers, including MCP-1 and Hcy, were significantly increased in both the in vivo and in vitro models, while the BDNF level was significantly decreased compared with the sham or vehicle models. Microscopy, AO/EB staining, and flow cytometry analysis showed that severe cell damage occurred in OGD PC12 cells, and apoptosis played a major role in this environment. Further Western blot studies showed that the apoptosis-related Bax/Bcl-2 protein ratio and cleaved caspase-3 were significantly increased in the experiment. However, ligustrazine profoundly suppressed the imbalance of these biomarkers, reduced cell damage, decreased the Bax/Bcl-2, and downregulated cleaved caspase-3. Pro-and anti-apoptotic biomarkers of multiple pathways including BDNF, MCP-1, and Hcy played a joint role in triggering the activation of the mitochondria-related Bax/Bcl-2 and caspase-3 apoptosis pathway in VD. Ligustrazine attenuated VD by comprehensively regulating BDNF, MCP-1, and Hcy and inactivating the Bax/Bcl-2 and caspase-3 apoptosis pathway. Our data provide novel insight into ligustrazine, which is a promising neuroprotective agent for VD disease treatment strategies.

3-<em>n</em>-butylphthalide exerts neuroprotective effects by enhancing anti-oxidation and attenuating mitochondrial dysfunction in an in vitro model of ischemic stroke

“…These findings may help to explain how the drug can restore microcirculation in cerebral ischemic area and improve brain energy metabolism after acute ischemic stroke. 14 In our in vitro model involving PC12 neuronal cells exposed to OGD, 19 this exposure induced increased activity of caspase-3, while NBP pretreatment reversed this. Caspase-3 is a major cell death effector protease, 20 and its activation is associated with apoptotic cell death phenotypes.…”

Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus

“…As apoptosis is regulated by a cascade of genes, we further examined the mRNA expression of caspase-8, caspase-3, Bax, and Bcl-2, to explore the apoptotic pathway. Caspase-8 is the upstream molecule that further activates caspase-3, a key apoptosis executive molecular [47,48]. Furthermore, Bax and Bcl-2 are important mediators for apoptotic regulation.…”

Effect of yellowing time on bioactive compounds in yellow tea and their antiproliferative capacity in HepG2 cells

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