Submit Manuscript  

Article Details


Decrease in the Generation of Amyloid-β Due to Salvianolic Acid B by Modulating BACE1 Activity

[ Vol. 14 , Issue. 11 ]

Author(s):

Siva Sundara Kumar Durairajan, Venkat Reddy Chirasani, Sravan Gopalakrishnan Shetty, Ashok Iyaswamy, Sandeep Malampati, Juxian Song, Liangfeng Liu, Jiandong Huang, Sanjib Senapati and Min Li   Pages 1229 - 1237 ( 9 )

Abstract:


Objective: Generation and accumulation of the amyloid-β (Aβ) peptide after proteolytic processing of the full length amyloid precursor protein (FL-APP) by β-secretase (β-site APP cleaving enzyme or BACE1) and γ-secretase are the main causal factors of Alzheimer's disease (AD). Thus, inhibition of BACE1, a rate-limiting enzyme in the production of Aβ, is an attractive therapeutic approach for the treatment of AD. Recent studies suggest that salvianolic acid B (Sal B) is isolated from the radix of Salvia miltiorrhiza Bunge, a Chinese herbal medicine commonly used for the treatment of cardiovascular, cerebrovascular and liver diseases in China.

Method: In this study, we discovered that Sal B acted as a BACE1 modulator and reduced the level of secreted Aβ in two different Swedish APP (SwedAPP) mutant cell lines. Using N2a-mouse and H4- human neuroglioma cell lines expressing SwedAPP, it was demonstrated that Sal B significantly and dose-dependently decreased the generation of extracellular Aβ, soluble APPβ (by-product of APP cleaved by BACE1), and intracellular C-terminal fragment β from APP without influencing α-secretase and γ-secretase activity and the levels of FL-APP. In addition, using protein-docking, we determined the potential conformation of Sal B on BACE1 docking and revealed the interactions of Sal B with the BACE1 catalytic center.

Results: The docking provides a feasible explanation for the experimental results, especially in terms of the molecular basis of Sal B's action. Our results indicate that Sal B is a BACE1 inhibitor and, as such, is a promising candidate for the treatment of AD

Keywords:

Aβ generation, BACE-1, Docking, Salvianolic acid B, Soluble amyloid precursor protein-β, Traditional Chinese medicine.

Affiliation:

Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, No.7, Baptist University Road, Kowloon Tong, Hong Kong, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Neuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Neuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Neuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Neuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Neuroscience Research Laboratory, Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, No.7, Baptist University Road, Kowloon Tong, Hong Kong



Read Full-Text article