Abstract
Resveratrol is a natural polyphenol in lots of foods and traditional Chinese medicines, which has shown promising treatment for neurodegenerative diseases (NDs). However, the molecular mechanisms of its action have not been systematically studied yet. In order to elucidate the network pharmacological prospective effects of resveratrol on NDs, we assessed of pharmacokinetics (PK) properties of resveratrol, studied target prediction and network analysis, and discussed interacting pathways using a network pharmacology method. Main PK properties of resveratrol were acquired. A total of 13,612 genes related to NDs, and 138 overlapping genes were determined through matching the 175 potential targets of resveratrol with disease-associated genes. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to obtain more in-depth understanding of resveratrol on NDs. Accordingly, nodes with high degrees were obtained according using a PPI network, and AKT1, TP53, IL6, CASP3, VEGFA, TNF, MYC, MAPK3, MAPK8, and ALB were identified as hub target genes, which showed better affinity with resveratrol in silico studies. In addition, our experimental results demonstrated that resveratrol markedly enhanced the decreased levels of Bcl-2 and significantly reduced the increased expression of Bax and Caspase-3 in hippocampal neurons induced by glutamate exposure. Western blot results confirmed that resveratrol inhibited glutamate-induced apoptosis of hippocampal neurons partly by regulating the PI3K/AKT/mTOR pathway. In conclusion, we found that resveratrol could target multiple pathways forming a systematic network with pharmacological effects.
Highlights
Neurodegenerative diseases (NDs) are multifactorial debilitating disorders that are characterized by progressive dysfunction and neuronal injury, which preferentially affect the normal functioning of the brain including learning and memory (Jakaria et al, 2019)
OB is the primary feature of oral medications because it plays a critical part in assessing the effectiveness of MW, molecular weight; AlogP value represents the partition coefficient between octanol and water; Hdon and Hacc are measures of the hydrogen-bonding ability of a molecule expressed in terms of number of possible hydrogen-bond donors and acceptors, respectively; OB, oral bioavailability; Caco-2, Caco-2 permeability; BBB, blood-brain barrier; drug likeness (DL), drug-likeness; FASA, fractional water accessible surface area of all atoms with negative partial charge; TPSA is a physico chemical property describing the polarity of molecules; RBN is the number of bonds which allow free rotation around themselves; HL, drug half-life
The results revealed that docking scores of resveratrol with AKT1, tumor antigen p53 (TP53), interleukin 6 (IL6), CASP3, vascular endothelial growth factor A (VEGFA), tumor necrosis factor (TNF), myc proto-oncogene protein (MYC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 8 (MAPK8), and ALB ranged from −4.8 to −8.9
Summary
Neurodegenerative diseases (NDs) are multifactorial debilitating disorders that are characterized by progressive dysfunction and neuronal injury, which preferentially affect the normal functioning of the brain including learning and memory (Jakaria et al, 2019). Network pharmacology as an emerging discipline located on the general concepts of systems biology (Zhou et al, 2019), which was utilized to systematically evaluate pharmacological effects of multiingredient medicine (Zhang R. et al, 2019). It has been provided lately for revealing the molecular mechanisms of various complicated chronic diseases, such as NDs and cardiocerebral vascular diseases (Wang W. et al, 2019). Resveratrol was hypothesized to have therapeutic effects on NDs through multiple-targets mechanism. The potential candidate target genes were predicted via network pharmacology databases.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
