Natural Products Molecular Targets Identification by Quantitative Pathway Analysis
Grant Data
Project Title
Natural Products Molecular Targets Identification by Quantitative Pathway Analysis
Principal Investigator
Dr Lok, Chun Nam
(Principal Investigator (PI))
Co-Investigator(s)
Dr Fung Eva Yi Man
(Co-Investigator)
Duration
36
Start Date
2015-09-01
Amount
782205
Conference Title
Natural Products Molecular Targets Identification by Quantitative Pathway Analysis
Presentation Title
Keywords
Bioinformatics, HPLC/MS-MS, Molecular target, Proteomics, Traditional Chinese Medicine
Discipline
Proteomics
Panel
Biology and Medicine (M)
HKU Project Code
17127915
Grant Type
General Research Fund (GRF)
Funding Year
2015
Status
Completed
Objectives
1 Aim 1: To develop a method and optimize procedures for identification of molecular targets using MS-based proteomics expression data. To understand the molecular target and thus the mechanism-of-action of a drug is crucial for drug development. In preliminary studies, we used camptothecin, an alkaloid with known target, as a model for development and optimization of methods and procedures for drug target identification. With the help of bioinformatics tools and high through-put MS-based proteomics techniques, the target identification procedure has been optimized. And the known target of camptothecin, topoisomerase I, is identified as the main target from the proteome profiles of camptothecin treated cancer cells. The procedures has been applied to study capsaicin, an alkaloid found in chili peppers to confirm that the methods applicable to compounds other than camptothecin and to refine the developed procedures. The results will be compared with the findings on studies of capsaicin in literature. And in turn the procedures will be refined to improve the accuracy and significance of the hypothetic molecular target prediction. 2 Aim 2. To apply the optimized procedure to search for novel molecular targets of selected bioactive TCM components. The same procedure has been applied to another bioactive component in herbs, corydaline, an alkaloid found in corydalis rhizome. Our preliminary study with corydaline hypothesized the proto-oncogene c-fos as one of the potential targets. Other than corydaline, a few bioactive TCM components will be selected based on their cytotoxcities, and the target identification procedure will be applied subsequently. Several TCM has been targeted based on their pharmacological effects stated in traditional Chinese medicinal literature. The selected TCM including: Dendrobium nobile (Shihu), Juncus effusus (Dengxincao), Lithospermum erythrorhizon (Zicao), Houttuynia cordata (Yuxingcao) and dandelion (Pugongying), their major bioactive components will be used in the proposed research. 3 Aim 3. To validate the potential targets of the selected bioactive TCM components and to elucidate their mechanism-of-action. A potential targets generation method is helpful in providing research direction to study the mechanism-of-action of a drug. The proposed potential molecular targets found in Aim 2 will be validated through orthogonal biological assays. And the mechanism-of-action of the bioactive TCM components will be elucidated through the identified targets. We are validating the proto-oncogene c-fos as a target of corydaline. Our preliminary results showed that corydaline inhibits a c-fos related transcriptional activity.