Apigenin exhibits memory enhancing activity through the restoration of oxido-endocrine balance and upregulation of BDNF/ERK/CREB signalling pathways in stressed mice.

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.