The flavonoids of okra insulates against oxidative stress, neuroinflammation and restores BDNF levels in Aβ1-42 induced mouse model of Alzheimer's disease

Abstract

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 Aβ_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-α (TNF-α), interleukin-1β (IL-1β), 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-κB), 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-3β (GSK-3β) were studied by western blot. Histopathological changes were observed by H.E. straining. The results showed that intracerebroventricular injection of Aβ_1-42 was effective in producing memory deficits in mice. Besides, Aβ_1-42 exposure could significantly increase the levels of NF-κB, TNF-α, IL-1β, 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-3β signaling pathways in the hippocampus and cortex. Nevertheless, chronic administration of FOF (100 or 300 mg/kg, i.g.) significantly prevented Aβ_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/GSK3β pathways, as well as alleviation of oxidative stress and neuroinflammation.

Keywords: BDNF; Flavonoids of okra fruit; Learning and memory impairment; Neuroinflammation; Oxidative stress.