In silico target fishing for the potential bioactive components contained in Huanglian Jiedu Tang (HLJDD) and elucidating molecular mechanisms for the treatment of sepsis.
10.1016/S1875-5364(15)60004-8
- Author:
Shi-Tang MA
1
,
2
;
Cheng-Tao FENG
3
;
Guo-Liang DAI
4
;
Yue SONG
5
;
Guo-Liang ZHOU
5
;
Xiao-Lin ZHANG
5
;
Cheng-Gui MIAO
5
;
Hao YU
6
;
Wen-Zheng JU
7
Author Information
1. Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China
2. College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China.
3. Anhui University of Science and Technology, Huainan 232001, China.
4. College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China.
5. Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China.
6. Food and Drug College, Anhui University of Science and Technology, Fengyang 233100, China. Electronic address: yhz_1230@163.com.
7. College of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing 210023, China. Electronic address: nothingchina@126.com.
- Publication Type:Journal Article
- Keywords:
In silico target fishing;
Natural products;
PGE(2) inhibition;
Sepsis target
- MeSH:
Anti-Inflammatory Agents, Non-Steroidal;
pharmacokinetics;
Berberine;
analogs & derivatives;
pharmacokinetics;
Dinoprostone;
biosynthesis;
Drugs, Chinese Herbal;
chemistry;
pharmacokinetics;
Humans;
KB Cells;
Platelet Membrane Glycoproteins;
drug effects;
Protein Transport;
Receptors, G-Protein-Coupled;
drug effects;
Receptors, Thromboxane A2, Prostaglandin H2;
drug effects;
Sepsis;
drug therapy;
metabolism;
Tetradecanoylphorbol Acetate;
pharmacokinetics
- From:
Chinese Journal of Natural Medicines (English Ed.)
2015;13(1):30-40
- CountryChina
- Language:English
-
Abstract:
The present study was designed to target fish for potential bioactive components contained in a Huang Lian Jie Du decoction (HLJDD) and identify the underlying mechanisms of action for the treatment of sepsis at the molecular level. he bioactive components database of HLJDD was constructed and the sepsis-associated targets were comprehensively investigated. The 3D structures of the PAFR and TXA2R proteins were established using the homology modelling (HM) method, and the molecular effects for sepsis treatment were analysed by comparing the bioactive components database and the sepsis targets using computational biology methods. The results of the screening were validated with biological testing against the human oral epidermal carcinoma cell line KB in vitro. We found that multiple bioactive compounds contained in the HLJDD interacted with multiple targets. We also predicted the promising compound leads for sepsis treatment, and the first 28 compounds were characterized. Several compounds, such as berberine, berberrubine and epiberberine, dose-dependently inhibited PGE2 production in human KB cells, and the effects were similar in the presence or absence of TPA. This study demonstrates a novel approach to identifying natural chemical compounds as new leads for the treatment of sepsis.
