To explore the Radix Paeoniae Rubra-Flos Carthami herb pair's potential mechanism in the treatment of ischemic stroke by network pharmacology and molecular docking technology

Abstract

To explore the Radix Paeoniae Rubra-Flos Carthami herb pair's (RPR-FC) potential mechanism in treating ischemic stroke (IS) by network pharmacology and molecular docking technology. The Traditional Chinese Medicine Systems Pharmacology Database was used to screen the active components of the RPR-FC, and Cytoscape 3.8 software was used to construct a network map of its active components and targets of action. The GeneCards and OMIM databases were used to identify disease targets of IS, and the common targets were chosen as research targets and imported into the STRING database to construct a protein–protein interaction network map of these targets. R language software was used to analyze the enrichment of GO terms and KEGG pathways, and explore the mechanisms of these targets. Molecular docking technology was used to verify that the RPR-FC components had a good bonding activity with their potential targets. A total of 44 active components, which corresponded to 197 targets, were identified in the RPR-FC. There were 139 common targets between the herb pair and IS. GO functional enrichment analysis revealed 2253 biological process entries, 72 cellular components entries, and 183 molecular functions entries. KEGG pathway enrichment analysis was mainly related to the NF-kappa B signaling pathway, the TNF signaling pathway, apoptosis, the MAPK signaling pathway, the PI3K-Akt signaling pathway, the VEGF signaling pathway, etc. The molecular docking results showed the components that docked well with key targets were quercetin, luteolin, kaempferol, and baicalein. The active components (quercetin, luteolin, kaempferol, and baicalein) of the RPR-FC and their targets act on proteins such as MAPK1, AKT1, VEGFA, and CASP3, which are closely related to IS. 1 These targets are closely related to the NF-kappa B signaling pathway, the MAPK signaling pathway, the PI3K-Akt signaling pathway, the VEGF signaling pathway, and other signaling pathways. These pathways are involved in the recovery of nerve function, angiogenesis, and neuronal apoptosis and the regulation of inflammatory factors, which may have a therapeutic effect on IS.

Effects of Moleac 901 after severe spinal cord injury on chronic phase in Wistar rats

“…Neuroprotective SY intervention increases Bcl-2, inhibits Bax, and activates caspase-3. SY mechanism in SCI-induced inflammation by restricting TNF-a, suppressing the high mobility group box 1 protein-TLR4-NF-kB signal pathway, and lowering ROS [ 40 ]. MLC901 suppresses apoptosis and promotes neurite development by activating the BDNF/TrkB/ERK pathway.…”

“… Radix salviae miltorrhizae (RSM) [ 39 , 47 , 48 ] Salvianolic acid Inflammation, edema, oxidative stress Inhibits ERK, inhibits the NF-κB path, decreases MDA expression. Radix paeonieae rubra (RPR) [ 39 , 40 , [47] , [48] , [49] ] Paeoniflorin Apoptosis, inflammation Reducing Caspase-3, lowering TLR mediated signals. Rhizoma chuanxiong (RC) [ 39 , 42 ] Alkaloid Tetra-methylpyrazine , Ferulic acid, senkyunolide I, dan ligustilide Apoptosis, inflammation Increases BCL-2, decreases Caspase-3, activation of the P13K/AKT pathway, interacting with the ALB, AKT1, MAPK1, MMP9, and EGFR genes decreases proinflammatory cytokines (IL-1mit and TNF-α) and increases IL-10).…”

“… Angelicae sinensis radix (ASR) [ 15 , 50 ] Polysaccharides, Z-Stillicide, dan ferulic acid Apoptosis, inflammation, regenerative Activation of the P13K/AKT pathway, inhibits the NF-κB path, lowering MPO, helping the differentiation of stem cells. Carthamus tinctorius (SY) [ 9 , 40 , 51 ] Safflower Yellow Apoptosis, myelin regeneration Increasing BCL-2, lowering Bax and Caspase-3, triggers growth and expansion of neurit through the activation of the BDNF/TrkB/ERK pathway. Radix polygalae (RP) [ 52 , 53 ] Sibiricose A5 dan 3,6′- disinapoyl sucrose Inflammation Activation of TrkB/CREB signals causes M2 dominance (increases IL-4, NGF, and BDNF).…”

Detection of ryanodine receptor G4911E and I4754M mutation sites and analysis of binding modes of diamide insecticides with RyR on Galeruca daurica (Coleoptera: Chrysomelidae)

“…MEGA X was applied to construct phylogenetic tree ( Kumar et al, 2018 ); Open Babel-2.4.1 was used to convert the file format of the chemical structure type ( O’Boyle et al, 2011 ); The 3D protein crystal structure was visualized by Pymol-2.1.0 ( Delano, 2002 ); Modeller (Version-10.2) was used for homologous modeling ( Chen et al, 2021 ); Autodock Tool-1.5.7 ( Morris et al, 2009 ) and Autodock vina 1.1.2 ( Trott and Olson., 2010 ) were used for molecular docking; AlphaFold2 was applied for deep learning modeling ( Jumper et al, 2021 ).…”

“…With the development of bioinformatics and computer simulation technology, protein homology modeling, molecular docking and other technical tools are becoming increasingly sophisticated. Novel ideas for studying pest resistance mechanisms to insecticides are proposed by predicting the binding pattern of receptors and ligands ( Chen et al, 2021 ). Homology modeling uses the crystal structure of a protein molecule with high homology to its amino acid sequence as a template for sequence alignment, and predicts the structure of an unknown, homologous protein from the conserved domain of known crystal protein molecule ( Boris and Ke, 2022 ).…”