Akebia saponin D reverses corticosterone hypersecretion in an Alzheimer's disease rat model

Background: Glucocorticoid hormones are implicated in the pathogenesis of Alzheimer's disease (AD) and other diseases including diabetes, hyperlipidemia, and osteoporosis. Akebia saponin D (ASD) possesses numerous pharmacological activities, including as an anti-AD, anti-hyperlipidemia, anti-diabetes, and anti-osteoporosis agent. The anti-AD effect of ASD is possibly through its regulation of glucocorticoid levels. Purpose: The present study was undertaken to investigate the neuroprotective effects of ASD on A beta(25-35)-induced cognitive deficits and to elucidate its underlying mechanism of action. Methods: The AD rat model was established by an intracerebroventricular injection of A beta(25-35) into the lateral ventricles. Spatial learning and anxiety state were assessed by Morris water maze task and elevated plus-maze assay, respectively. The degree of hypertrophy of adrenal gland was analyzed using the viscera coefficient. Corticosterone and ACTH concentrations in the plasm were measured using biochemical assay kits. The activity of 11 beta-hydroxysteroid dehydrogenase type-1 (11 beta-HSD1) in liver and groin fat pad was assessed by measuring cortisol production. Results: Compared with the control group, AD rats displayed significant spatial learning and reference memory impairments, serious anxiety disorders, obvious hypertrophy of adrenal gland, elevated corticosterone and ACTH levels in the plasma, and increased 11 beta-HSD1 activity in liver and groin fat pad. ASD could significantly ameliorate the memory deficits and anxiety symptoms, markedly reduce the viscera coefficient of adrenal gland, observably decrease corticosterone and ACTH concentrations, and showed no effect on the activity of 11 beta-HSD1. Conclusions: These results indicate that ASD might exert a significant neuroprotective effect on cognitive impairment, driven in part by reducing systemic corticosterone level by down-regulation of the hypothalamic-pituitary-adrenal (HPA) axis.