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Uncovering potential anti-neuroinflammatory components of Modified Wuziyanzong Prescription through a target-directed molecular docking fingerprint strategy
- Source :
- Journal of pharmaceutical and biomedical analysis. 156
- Publication Year :
- 2018
-
Abstract
- Neuroinflammation is a main factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer disease. Our previous studies indicated that the modified Wuziyanzong Prescription (MWP) can suppress neuroinflammatory responses via nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. However, the anti-neuroinflammatory components of MWP remain unclear. Herein, a target-directed molecular docking fingerprint (TMDF) strategy, via integrating the chemical profiling and molecular docking approaches, was developed to identify the potential anti-neuroinflammatory components of MWP. First, as many as 120 possible structures, including 49 flavonoids, 28 phenylpropionic acids, 18 amides, 10 carotenoids, eight phenylethanoid glycosides, four lignans, two iridoids, and one triterpenoid were deduced by the source attribution and structural classification-assisted strategy. Then, their geometries were docked against five major targets of the NF-κB and MAPKs signaling cascades, including p38-α, IKKβ, ERK1, ERK2, and TRAF6. The docking results revealed diverse contributions of different components towards the protein targets. Collectively, prenylated flavonoids showed intensive or moderate anti-neuroinflammatory activities, while phenylpropanoids, amides, phenylethanoid glycosides, lignans, and triterpenoids exhibited moderate or weak anti-neuroinflammatory effects. The anti-neuroinflammatory activities of four retrieved prenylated flavonoids were tested by Western blotting assay, and the results mostly agreed with those predicted by the docking method. These gained information demonstrates that the established TMDF strategy could be a rapid and feasible methodology to investigate the potential active components in herbal compound prescriptions.
- Subjects :
- 0301 basic medicine
Cell Survival
MAP Kinase Signaling System
p38 mitogen-activated protein kinases
Clinical Biochemistry
Phytochemicals
Anti-Inflammatory Agents
Drug Evaluation, Preclinical
Pharmaceutical Science
Computational biology
010402 general chemistry
01 natural sciences
Analytical Chemistry
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Mice
Triterpenoid
Prenylation
Drug Discovery
Animals
Spectroscopy
chemistry.chemical_classification
Inflammation
Chemistry
Kinase
NF-kappa B
Glycoside
Neurodegenerative Diseases
Phenylethanoid
0104 chemical sciences
I-kappa B Kinase
Molecular Docking Simulation
030104 developmental biology
Neuroprotective Agents
Docking (molecular)
Feasibility Studies
Signal transduction
Drugs, Chinese Herbal
Subjects
Details
- ISSN :
- 1873264X
- Volume :
- 156
- Database :
- OpenAIRE
- Journal :
- Journal of pharmaceutical and biomedical analysis
- Accession number :
- edsair.doi.dedup.....b331ba89a7bbe2902188a0f2ea97c136