Khatoon Saima, Samim Mohammed, Dahalia Mansi
Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India.
Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India.
Eur J Pharmacol. 2023 Apr 5;944:175583. doi: 10.1016/j.ejphar.2023.175583. Epub 2023 Feb 8.
Fisetin is a flavonoid molecule known to be neuroprotective by its multiple mechanisms. The present study was designed to explore the effect of fisetin in the pentylenetetrazole (PTZ) kindling-induced cognitive dysfunction in mice.
Kindling was established by the intraperitoneal administration of PTZ in a subconvulsive dose (25 mg/kg). Mice were administered fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable cognition-enhancing effect. The kindled mice were evaluated for cognition using behavioral tests-elevated plus maze and passive avoidance response. Then, the oxidative stress markers, gene expressions and neurotransmitters levels were estimated in the hippocampus and cortex of mice.
Passive avoidance response and elevated plus maze paradigms showed that fisetin administration improved the cognitive function in kindled mice. The increased levels of lipid peroxidation and protein carbonyl were modulated upon fisetin administration through increasing the levels of antioxidants (reduced glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase) in the hippocampus and cortex of kindled mice. Upregulated gene expressions of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were observed in the hippocampus and cortex of fisetin-administered mice which play a crucial role in cognitive function. Furthermore, alterations of neurotransmitter levels (dopamine, GABA, and glutamate) and acetylcholinesterase (AchE) were ameliorated by fisetin administration in the hippocampus and cortex of kindled mice.
Our findings suggest a therapeutic potential of fisetin against cognitive dysfunction associated with PTZ-induced kindling.
漆黄素是一种黄酮类分子，已知其通过多种机制具有神经保护作用。本研究旨在探讨漆黄素对戊四氮（PTZ）点燃诱导的小鼠认知功能障碍的影响。
通过腹腔注射亚惊厥剂量（25mg/kg）的PTZ建立点燃模型。给小鼠灌胃漆黄素（5、10和20mg/kg）以研究其可能的认知增强作用。使用行为学测试——高架十字迷宫和被动回避反应对点燃小鼠的认知功能进行评估。然后，测定小鼠海马和皮层中的氧化应激标志物、基因表达和神经递质水平。
被动回避反应和高架十字迷宫实验表明，给予漆黄素可改善点燃小鼠的认知功能。通过提高点燃小鼠海马和皮层中抗氧化剂（还原型谷胱甘肽、谷胱甘肽还原酶、谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶）的水平，给予漆黄素可调节脂质过氧化和蛋白质羰基化水平的升高。在给予漆黄素的小鼠海马和皮层中观察到环磷酸腺苷反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）的基因表达上调，它们在认知功能中起关键作用。此外，给予漆黄素可改善点燃小鼠海马和皮层中神经递质水平（多巴胺、γ-氨基丁酸和谷氨酸）的改变以及乙酰胆碱酯酶（AchE）的活性。
我们的研究结果表明漆黄素对PTZ诱导的点燃相关认知功能障碍具有治疗潜力。
