Bhratee Anjalee, Chatterjee Dhrita, Kaur Romanpreet, Singh Shamsher
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Metab Brain Dis. 2025 Mar 20;40(4):155. doi: 10.1007/s11011-025-01579-w.
Cognitive impairment is characterized by memory loss and difficulty in focusing, remembering, adhering to directions, and solving problems; commonly seen in an elderly population. Apigenin (APG) (4', 5, 7-trihydroxyflavone) is a flavonoid with several positive health benefits, including chemoprevention, antioxidant and can suppress inflammatory responses by inhibiting TNF-α and IL-1β levels. In this experimental study, we observed the possible neuroprotective effects of APG in the zebrafish model exposed to Lansoprazole (LPZ), a proton pump inhibitor known to induce cognitive impairment through hyperactivation of GSK-3β pathway. This experiment involves 12 adult zebrafish per group, where one group received LPZ (100 mg) as a toxin for 7 days and APG (25, 50, and 100 mg/kg) as treatment, while DPZ (5 mg/kg) served as a standard comparison over the same period. Neurobehavioral tests such as T-Maze, Novel Tank Test (NTT), and Novel Object Recognition (NOR) were performed. Several biochemical assessments were also performed to evaluate the level of lipid peroxidation (LPO), glutathione (GSH), nitrite (NO), acetylcholinesterase activity (AChEs), catalase activity, neurotransmitters (GABA and glutamate), neuroinflammatory markers (IL-1β, TNF-α, and IL-10), and histopathological analysis. The results showed that apigenin enhanced memory function, improved neurotransmitter balance, decreased oxidative stress markers, regulated the production of proinflammatory cytokines, and inhibited GSK-3β activity. Additionally, the co-administration of a GSK-3β inhibitor further promoted neuroprotection and cognitive enhancement facilitated by apigenin, highlighting the importance of the GSK-3β signaling pathway. These findings highlight the potential of apigenin as a natural compound for mitigating cognitive dysfunction. However, this study should also include long-term toxicity assessments and deeper molecular analysis to elucidate Apigenin's mechanism of action fully. Future research should address these gaps to validate its therapeutic potential.
认知障碍的特征是记忆力丧失以及在集中注意力、记忆、遵循指示和解决问题方面存在困难；常见于老年人群。芹菜素（APG）（4'，5，7 - 三羟基黄酮）是一种具有多种有益健康作用的黄酮类化合物，包括化学预防、抗氧化作用，并且可以通过抑制肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平来抑制炎症反应。在本实验研究中，我们观察了芹菜素在暴露于兰索拉唑（LPZ）的斑马鱼模型中的可能神经保护作用，兰索拉唑是一种已知通过糖原合成酶激酶-3β（GSK-3β）途径过度激活而诱导认知障碍的质子泵抑制剂。本实验每组涉及12条成年斑马鱼，其中一组接受LPZ（100毫克）作为毒素处理7天，并接受芹菜素（25、50和100毫克/千克）作为治疗，而多潘立酮（DPZ）（5毫克/千克）在同一时期作为标准对照。进行了诸如T迷宫、新鱼缸试验（NTT）和新物体识别（NOR）等神经行为测试。还进行了多项生化评估，以评估脂质过氧化（LPO）水平、谷胱甘肽（GSH）、亚硝酸盐（NO）、乙酰胆碱酯酶活性（AChEs）、过氧化氢酶活性、神经递质（γ-氨基丁酸（GABA）和谷氨酸）、神经炎症标志物（IL-1β、TNF-α和IL-10）以及组织病理学分析。结果表明，芹菜素增强了记忆功能，改善了神经递质平衡，降低了氧化应激标志物水平，调节了促炎细胞因子的产生，并抑制了GSK-3β活性。此外，GSK-3β抑制剂的联合给药进一步促进了芹菜素所带来的神经保护和认知增强作用，突出了GSK-3β信号通路的重要性。这些发现突出了芹菜素作为一种减轻认知功能障碍的天然化合物的潜力。然而，本研究还应包括长期毒性评估和更深入的分子分析，以充分阐明芹菜素的作用机制。未来的研究应填补这些空白，以验证其治疗潜力。
