Affiliation:
1. Gansu University of Chinese Medicine Lanzhou China
2. Key Laboratory of Chemistry and Quality for Traditional Chinese Medicines of the College of Gansu Province Lanzhou China
3. Gansu Province Engineering Laboratory for TCM Standardization Technology and Popularization Lanzhou China
4. College of Veterinary Medicine Gansu Agricultural University Lanzhou China
Abstract
AbstractDanggui Buxue decoction (DBD) is a traditional Chinese medicine herbal decoction that has a good therapeutic effect on vascular dementia (VaD). However, its pharmacodynamic substances and underlying mechanisms are ambiguous. The work aimed to decipher the pharmacodynamic substances and molecular mechanisms of DBD against VaD rats based on gas chromatography–mass spectrometry metabonomics, network pharmacology, molecular docking, and experimental verification. The results indicated that DBD significantly improved the learning abilities and cognitive impairment in the VaD rat model. Integration analysis of the metabolomics and network pharmacology approach revealed that DBD might primarily affect arachidonic acid (AA) and inositol phosphate metabolic pathways by regulating the platelet activation signaling pathways. Six core targets (TNF [tumor necrosis factor], IL‐6 [interleukin 6], PTGS2 [prostaglandin‐endoperoxide synthase 2], MAPK1, MAPK3, and TP53) in the platelet activation signaling pathways also had a good affinity to seven main active components (saponins, organic acids, flavonoids, and phthalides) of DBD through the verification of molecular docking. Enzyme‐linked immunosorbent assay results (ELISA) showed that the levels of TNF, IL‐6, PTGS2, thromboxane B2, and caspase‐3 in the platelet activation signaling pathway can be regulated by DBD. Our results indicated that DBD treated VaD mainly by modulating the platelet activation signaling pathway, and AA and inositol phosphate metabolism.
Subject
Clinical Biochemistry,Drug Discovery,Pharmacology,Molecular Biology,General Medicine,Biochemistry,Analytical Chemistry