Apigenin restores memory function in stressed mice

Abstract

AbstractBackgroundStress, a known cause of neuropsychiatric disorders, is associated with cognitve dysfunction, neuroendocrine systems breakdown and altered brain oxidative status and proteins (Roozendaal, 2002; Radecki et al., 2005; Lupien et al., 2007). Apigenin (API), a natural flavonoid, with diverse biological activity, is thought to possess neuroprotective potentials (Li et al., 2015). This study investigated whether API administration abrogates chronic unpredictable mild stress (CUMS)‐induced cognitive impairment, as well as exploring its probable underlying mechanisms.MethodSwiss male mice (n = 10) were treated with API (12.5 ‐ 25 mg/kg, intraperitoneally) 30 min before exposure to CUMS daily for 14 days, thereafter tested for memory function using the Y‐maze and novel object recognition (NOR) tests. Levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and corticosterone levels were assessed using enzyme‐linked immunosorbent assay. The expressions of brain derived neurotrophic factor (BDNF), phosphorylated extracellular signal‐regulated kinase (pERK), and cAMP response element‐binding protein (pCREB) were assessed using immunohistochemistry.ResultCUMS produced cognitive impairment in mice as shown in the Y‐maze and NOR tests. CUMS significantly elevated MDA, and serum corticosterone levels, including reducing GSH and SOD levels, decreasing BDNF, pERK, and pCREB levels in the prefrontal cortex and hippocampus. However, chronic administration of API significantly prevented all these CUMS‐induced behavioral and biochemical alterations.ConclusionAPI may be a potential therapeutic agent for cognitive disturbances as seen within the stress model and its neuroprotective effect was partly mediated by restoring oxidative status, serum corticosterone levels, up‐regulating BDNF, pCREB and pERK levels.