Neuroprotective role of chlorogenic acid against hippocampal neuroinflammation, oxidative stress, and apoptosis following acute seizures induced by pentylenetetrazole.
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引用次数: 0
Abstract
This study investigated the neuroprotective effect of chlorogenic acid (CGA) on pentylenetetrazole (PTZ)-induced acute epileptic seizures in mice. Epileptic animals received CGA (200 mg/kg) or sodium valproate (standard antiepileptic agent, 200 mg/kg) for four weeks. Results revealed that pre-administration of CGA significantly reversed the behavioral changes following pentylenetetrazole (PTZ) injection. Further, CGA pre-treatment caused significant increases in acetylcholinesterase (AChE) activity and brain-derived neurotrophic factor (BDNF) levels, along with marked increases in dopamine, norepinephrine, and serotonin levels. Additionally, the increased antioxidant enzymes activities, along with higher glutathione (GSH) contents and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, were indicative of a notable improvement in the cellular antioxidant defense in mice treated with CGA. These results were associated with lowered malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, epileptic mice that received CGA showed significant declines in the content of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa-B (NF-κB), besides downregulating inducible nitric oxide synthase (iNOS) expression. Remarkably, CGA counteracted hippocampal apoptosis by lessening the levels of pro-apoptotic biomarkers [Bcl-2-associated X protein (Bax) and caspase-3] and increasing the anti-apoptogenic marker level of B-cell lymphoma 2 (Bcl-2). The hippocampal histopathological findings corroborated the abovementioned changes. In sum, these findings suggest that CGA could mediate the neuroprotective effect against PTZ-induced epilepsy via modulation of neurotransmitters, oxidative damage, neuroinflammation, and apoptosis. CGA, therefore, could be considered a valuable antiepileptic therapeutic supplement.
期刊介绍:
Metabolic Brain Disease serves as a forum for the publication of outstanding basic and clinical papers on all metabolic brain disease, including both human and animal studies. The journal publishes papers on the fundamental pathogenesis of these disorders and on related experimental and clinical techniques and methodologies. Metabolic Brain Disease is directed to physicians, neuroscientists, internists, psychiatrists, neurologists, pathologists, and others involved in the research and treatment of a broad range of metabolic brain disorders.