Yuhui Wang1, Jinyang Shen2, Xiaolin Yang3, Ye Jin4, Zhonglin Yang2, Rufeng Wang5, Fuming Zhang6, Robert J Linhardt7. 1. Department of Pharmacology, Guilin Medical University, Guilin, China. 2. State Key laboratory of natural Medicines, China Pharmaceutical University, Nanjing, China. 3. Jiangsu Key Laboratory of Research and Development in Marine Bio-resource Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, China; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. 4. Pharmacy Department, Yangzhou Hospital of Traditional Chinese Medicine, Yangzhou, China. 5. Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Material Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. Electronic address: sjy898989@sina.com. 6. Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. 7. Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Chemistry, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA; Departments of Biology, Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute, Troy, NY, USA.
Abstract
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 Aβ25-35-induced cognitive deficits and to elucidate its underlying mechanism of action. METHODS: The AD rat model was established by an intracerebroventricular injection of Aβ25-35 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 11β-hydroxysteroid dehydrogenase type-1 (11β-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 11β-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 11β-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.
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 Aβ25-35-induced cognitive deficits and to elucidate its underlying mechanism of action. METHODS: The AD rat model was established by an intracerebroventricular injection of Aβ25-35 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 11β-hydroxysteroid dehydrogenase type-1 (11β-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 11β-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 11β-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.