The flavonoids of okra insulates against oxidative stress, neuroinflammation and restores BDNF levels in A beta(1-)(42) induced mouse model of Alzheimer's disease

摘要

Okra (Abelmoschus esculentus [L.] Moench.) has been used as a natural drug in East or West Africa for many centuries, as well as consumed in most areas of the world as a tropical vegetable. The study aimed to evaluate whether the flavonoids of okra fruit (FOF) administration influence A beta(1-42)-induced learning and memory impairment, and explore the underlying mechanisms. The Y-maze task and the Morris water maze test were used for evaluating cognition processes. The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) were detected by ELISA kits. The expressions of nuclear factor kappa-light chain-enhancer of activated B (NF-kappa B), brain-derived neurotrophic factor (BDNF), cAMP-response element-binding protein (CREB), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), glycogen synthase kinase-3 beta (GSK-3 beta) were studied by western blot. Histopathological changes were observed by H.E. straining. The results showed that intracerebroventricular injection of A beta(1-42) was effective in producing memory deficits in mice. Besides, A beta(1-42) exposure could significantly increase the levels of NF-kappa B, TNF-alpha, IL-1 beta, and decreased T-AOC, the activities of SOD and GSH-Px in the hippocampus and cortex. Furthermore, the level of BDNF was also reduced, accompanied by down-regulated CREB/ERK and PI3K/AKT/GSK-3 beta signaling pathways in the hippocampus and cortex. Nevertheless, chronic administration of FOF (100 or 300 mg/kg, Lg.) significantly prevented A beta(1-42)-induced behavioral and biochemical alterations. It also suggested that FOF could improve the cognitive deficits in AD-like model mice, which might be mediated by regulation of BDNF levels in cortex and hippocampus and up-regulating of CREB/ERK and PI3K/AKT/GSK3 beta pathways, as well as alleviation of oxidative stress and neuroinflammation.