Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal the Protective Effect of Salvianolic Acid C in a Rat Model of Ischemic Stroke

Abstract

Salvianolic acid C (SAC) is a major bioactive component of Salvia miltiorrhiza Bunge (Danshen), a Chinese herb for treating ischemic stroke (IS). However, the mechanism by which SAC affects the IS has not yet been evaluated, thus a network pharmacology integrated molecular docking strategy was performed to systematically evaluate its pharmacological mechanisms, which were further validated in rats with cerebral ischemia. A total of 361 potential SAC-related targets were predicted by SwissTargetPrediction and PharmMapper, and a total of 443 IS-related targets were obtained from DisGeNET, DrugBank, OMIM, and Therapeutic Target database (TTD) databases. SAC-related targets were hit by the 60 targets associated with IS. By Gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment combined with the protein-protein interaction (PPI) network and cytoHubba plug-ins, nine related signaling pathways (proteoglycans in cancer, pathways in cancer, PI3K-Akt signaling pathway, Focal adhesion, etc.), and 20 hub genes were identified. Consequently, molecular docking indicated that SAC may interact with the nine targets (F2, MMP7, KDR, IGF1, REN, PPARG, PLG, ACE and MMP1). Four of the target proteins (VEGFR2, MMP1, PPARγ and IGF1) were verified using western blot. This study comprehensively analyzed pathways and targets related to the treatment of IS by SAC. The results of western blot also confirmed that the SAC against IS is mainly related to anti-inflammatory and angiogenesis, which provides a reference for us to find and explore the effective anti-IS drugs.

Network pharmacology and experimental evidence reveal the protective mechanism of Yi-Qi Cong-Ming decoction on age-related hearing loss

“…We found all docking values were lower than −5 kcal/mol, indicating a stable combination between core targets and core compounds (Yang et al. 2021 ; Zhang et al. 2021 ).…”

“…The minimum binding energy <−5.0 kcal/mol indicates a good binding affinity between receptor and ligand (Yang et al. 2021 ; Zhang et al. 2021 ).…”

Protective effect of Gastrodia elata Blume in a Caenorhabditis elegans model of Alzheimer's disease based on network pharmacology

“…Binding activity was expressed as binding energy; the lower the bonding energy, the more stable the docking module ( 29 ). In general, a docking energy <-5 kcal/mol indicates good docking ( 30 ).…”

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Gastrodia elata Blume in the treatment of ischemic stroke

“…The lower the binding energy, the more stable the docking module ( 30 , 31 ). In general, docking energy <-4.25 kcal/mol has docking activity, docking energy <-5 kcal/mol has good docking activity, while docking energy <-7 kcal/mol has very strong docking activity ( 32 ). Briefly, protein crystal structures of key genes were first obtained from the Protein Data Bank ( rcsb.org/ ), where water and other small molecules were removed using PyMOL and hydrogen atoms and charge manipulations were added using AutoDock.…”