| Author: | Cheung, Yuen Ching Karry |
| Title: | Pharmacological actions of Danggui Buxue Tang on oxygen-glucose deprivation and reoxygenation insulted mouse brain endothelial cells and ovariectomized Sprague Dawley rats |
| Advisors: | Mok, Daniel (FSN) |
| Degree: | M.Phil. |
| Year: | 2025 |
| Department: | Department of Food Science and Nutrition |
| Pages: | 172 pages : color illustrations |
| Language: | English |
| Abstract: | Menopause marks the permanent end of menstruation, resulting from decreased ovarian follicle activity and hormonal changes. The notable drop in estrogen level is a key risk factor for vascular dementia in menopausal women, which is characterized by cerebral hypoperfusion and disruption of the blood-brain barrier. While hormone replacement therapy remains the main treatment for menopausal symptoms, its long-term use is associated with increased risks of chronic diseases, limiting its clinical use in managing menopausal symptoms. Hence, there is an urgent need for safe and effective alternative therapies. Danggui Buxue Tang (DBT), a traditional Chinese herbal formula made from Astragali Radix (Huangqi) and Angelicae Sinensis Radix (Danggui), is known for its estrogenic and osteogenic properties and is widely used among menopausal women in Asia. Despite its widespread use, the effects of DBT on cerebral endothelial cells and cognitive function in ovariectomized rats are not yet fully understood. We hypothesized that DBT may help prevent menopause-related cognitive decline via upregulation of estrogen receptor (GPR30) and activating the Nrf2/HO-1 signalling pathway. The effects of DBT on the proliferation and migration of bEnd.3 cells were assessed using MTT and wound scratch assays, respectively. The expression of tight junction proteins were examined by western blotting, and ROS levels were evaluated using DCFDA staining. Our result showed that DBT (0.01-10 mg/mL) increased proliferation and migration of bEnd.3 cells in a concentration-dependent manner. Cell viability was markedly reduced by 60% following oxygen-glucose deprivation/reperfusion (OGD/R). DBT (0.01 – 3 mg/mL) suppressed the OGD/R-induced cell death in a concentration-dependent manner. Additionally, reductions in ZO-1 and Claudin-5 protein expression caused by OGD/R were normalized by DBT (0.1–3 mg/mL). Significant reductions in ROS levels were also observed when cells were treated with 0.3–3 mg/mL DBT. In in vivo study, ovariectomized Sprague Dawley rats demonstrated the effects of 8-week DBT administration on cognitive function and brain histology. Immunohistochemical analysis revealed that DBT treatment (3 g/mg/day) attenuated OVX-induced astrocyte reactivity, as evidenced by reduced GFAP expression and normalized astrocyte morphology in the hippocampus. While DBT showed limited effectiveness in restoring vascular density, it partially preserved vessel morphology as indicated by CD31 immunostaining. Besides, cognitive impairment was established in ovariectomized Sprague Dawley rats as shown by the results of the Morris water maze, novel object recognition and rotarod test. Following the 8-week feeding of DBT to ovariectomized rats, the cognitive deficits moderately improved. In conclusion, this study demonstrated, for the first time, that DBT as a classical Chinese formula can protect brain endothelial cells from OGD/R insult and improve cognitive functions in cognitively impaired ovariectomized rats. These findings support that DBT could be an alternative therapy for the management of menopause-associated vascular dementia. |
| Rights: | All rights reserved |
| Access: | open access |
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