Olayinka Juliet N, Eduviere Anthony T, Okosun Maureen O, Amadi Manuchim C, Ikpen Joshua O
Department of Pharmacology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Edo State, Nigeria.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 28. doi: 10.1007/s00210-025-03821-9.
Stress is linked to oxidative imbalance, neuroendocrine system malfunction, and cognitive dysfunction. It is a recognized cause of neuropsychiatric diseases. Natural flavonoid apigenin (API) has neuroprotective and antidepressant properties, but little is known about its potential in restoring memory function under stress-related circumstances. This study investigated the potentials of API administration in abrogating chronic unpredictable mild stress (CUMS)-induced cognitive impairment, including exploring its probable underlying mechanisms in mice. Male mice (n = 10) were treated with API (12.5-25 mg/kg, intraperitoneally) 30 min before exposure to CUMS daily for 14 days. Memory function (Y-maze and novel object recognition test (NOR)) was assessed. Concentrations of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), were estimated using a spectrophotometer. Corticosterone levels were assessed using an enzyme-linked immunosorbent assay (ELISA). Expressions of brain derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) were assessed using immunohistochemistry. In addition to elevating serum corticosterone and MDA levels, CUMS caused cognitive impairment in mice and decreased GSH, SOD, BDNF, ERK and CREB levels in the prefrontal cortex (PFC) and hippocampus. Administering API restored cognitive function, decreased serum corticosterone and MDA levels, as well as elevated GSH, SOD, BDNF, ERK and CREB levels in the mice brain. The restoration of oxidative, neuroendocrine balance, including upregulating BDNF, CREB, and pERK levels in the brain, all contributed to the neuroprotective effects of API. This suggests that, as shown by the stress paradigm, API may be a promising therapeutic agent for cognitive deficits.
应激与氧化失衡、神经内分泌系统功能紊乱以及认知功能障碍有关。它是神经精神疾病的一个公认病因。天然黄酮类芹菜素（API）具有神经保护和抗抑郁特性，但对于其在应激相关情况下恢复记忆功能的潜力知之甚少。本研究调查了给予API对消除慢性不可预测轻度应激（CUMS）诱导的认知障碍的潜力，包括探究其在小鼠体内可能的潜在机制。雄性小鼠（n = 10）在每天暴露于CUMS前30分钟腹腔注射API（12.5 - 25毫克/千克），持续14天。评估记忆功能（Y迷宫和新物体识别测试（NOR））。使用分光光度计估计丙二醛（MDA）、还原型谷胱甘肽（GSH）、超氧化物歧化酶（SOD）的浓度。使用酶联免疫吸附测定（ELISA）评估皮质酮水平。使用免疫组织化学评估脑源性神经营养因子（BDNF）、磷酸化细胞外信号调节激酶（ERK）和cAMP反应元件结合蛋白（CREB）的表达。除了升高血清皮质酮和MDA水平外，CUMS还导致小鼠认知障碍，并降低前额叶皮质（PFC）和海马体中的GSH、SOD、BDNF、ERK和CREB水平。给予API可恢复小鼠的认知功能，降低血清皮质酮和MDA水平，并提高小鼠脑中的GSH、SOD、BDNF、ERK和CREB水平。氧化、神经内分泌平衡的恢复，包括上调脑中的BDNF、CREB和pERK水平，均有助于API的神经保护作用。这表明，如应激模型所示，API可能是一种有前景的治疗认知缺陷的药物。
