Department of Biology, Faculty of Science, Al-Baha University, Al Baha, Saudi Arabia.
Metab Brain Dis. 2024 Oct;39(7):1307-1321. doi: 10.1007/s11011-024-01400-0. Epub 2024 Aug 12.
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.
这项研究旨在探讨绿原酸（CGA）对戊四氮（PTZ）诱导的小鼠急性癫痫发作的神经保护作用。癫痫动物接受 CGA（200mg/kg）或丙戊酸钠（标准抗癫痫药物，200mg/kg）治疗四周。结果表明，CGA 预处理显著逆转了戊四氮（PTZ）注射后的行为变化。此外，CGA 预处理可显著增加乙酰胆碱酯酶（AChE）活性和脑源性神经营养因子（BDNF）水平，并显著增加多巴胺、去甲肾上腺素和 5-羟色胺水平。此外，增加抗氧化酶活性、较高的谷胱甘肽（GSH）含量和上调核因子红细胞 2 相关因子 2（Nrf2）基因表达，表明 CGA 治疗的小鼠细胞抗氧化防御能力显著提高。这些结果与降低丙二醛（MDA）和一氧化氮（NO）水平有关。此外，接受 CGA 治疗的癫痫小鼠的白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和核因子 kappa-B（NF-κB）含量显著下降，诱导型一氧化氮合酶（iNOS）表达下调。值得注意的是，CGA 通过降低促凋亡生物标志物[Bcl-2 相关 X 蛋白（Bax）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）]水平和增加 B 细胞淋巴瘤 2（Bcl-2）的抗凋亡标志物水平来对抗海马细胞凋亡。海马组织病理学发现证实了上述变化。总之，这些发现表明，CGA 可能通过调节神经递质、氧化损伤、神经炎症和细胞凋亡来介导对 PTZ 诱导的癫痫的神经保护作用。因此，CGA 可以被认为是一种有价值的抗癫痫治疗补充剂。
