Protective Effect of Bacopasides on 7-Ketocholesterol Induced Damage in Human Brain Endothelial Cells

Abstract

Alzheimer’s disease (AD) is an irreversible, progressive brain disorder which leads to severe dementia. It is estimated to affect more than 100,000 people in Singapore and cost more than S$8 billion for its treatment for all Singaporeans by 2030. Recent studies demonstrated that altered cholesterol metabolism, which has been suggested to be caused by cholesterol autoxidation and oxidative stress in the brain, have been involved in AD progression. 7-Ketocholesterol (7KCh), abundantly found in deep-fried and over-cooked food, is a highly oxidised cytotoxic cholesterol which induces cell apoptosis and inflammation and is proven to result in AD. Previous researches demonstrated various pathway to inhibit 7KCh inflammation in human endothelial cells. However, there is a limited investigation on usage of phytochemical in botanical drugs against 7KCh. Bacopa monnieri has been used by Ayurvedic medical practitioners for centuries for a variety of purposes, including improving memory, reducing anxiety, and reducing inflammation. In this research, Bacopaside I (BI) and Bacopaside II (BII), two types of chemical extracts of Bacopa monnieri, are used to investigate the protective effect of BI and BII on 7KCh induced damage in human brain endothelial cells. HCMEC/d3 cell line is used as a model of the human blood–brain barrier. Cell culture is exposed to 7KCh, after which BI and BII were introduced. Cell viability test and quantitative real-time polymerase chain reaction test for pro-inflammatory cytokines, interleukin-6 and tumour necrosis factor-α were conducted. Results show that there is a significant protective effect of Bacopaside I on 7KCh damage in hCMEC/D3 cells, while Bacopaside II is deemed as ineffective against 7KCh induced damage. Therefore, Bacopa monnieri has the potential to become an effective medicinal approach to treat or mitigate AD.