the remaining 18 CRFrontiers in Pharmacology | frontiersin.orgDecember 2021 | Volume 12 | ArticleZeng et al.Chuanxiong Rhizoma Against Ischemic StrokeTABLE 1 | Pharmacological and molecular properties on the principal phytochemicals in CR. Compound Protocatechuic acid p-Hydroxybenzoic acid L-Tryptophan Vanillic acid Gallic acid Chlorogenic acid Caffeic acid Vanillin Ferulic acid Cryptochlorogenic acid three,5-O-Dicaffeoylquinic acid Senkyunolide I Senkyunolide H Coniferyl ferulate Senkyunolide A Butylphthalide Z-ligustilide Butylidenephthalide Neocnidilide Levistilide A Tetramethylpyrazine Formula C7H6O4 C7H6O3 C11H12N2O2 C8H8O4 C7H6O5 C16H18O9 C9H8O4 C8H8O3 C10H10O4 C16H18O9 C25H24O12 C12H16O4 C12H16O4 C20H20O6 C12H16O2 C12H14O2 C12H14O2 C12H12O2 C12H18O2 C24H28O4 C8H12N2 MW (g/mol) 154.12 138.12 204.23 168.15 170.12 354.31 180.16 152.15 194.18 354.31 516.45 224.25 224.25 356.37 192.25 190.24 190.24 188.22 194.27 380.48 136.19 Hdon three 2 3 two four six three 1 2 six 7 2 2 two 0 0 0 0 0 0 0 Hacc four 3 3 4 5 9 4 3 4 9 12 four 4 six two two 2 2 2 4 two Rbon 1 1 three three 1 5 2 2 three 5 9 2 2 eight 3 3 2 two 3 four 0 LogP 0.65 1.05 0.17 1.08 0.21 -0.38 0.93 1.two 1.36 -0.32 0.76 1.17 1.18 3.25 two.71 2.81 two.75 2.94 two.87 4.73 0.MW, molecule weight; Hdon, number of hydrogen bond donors; Hacc, number of hydrogen bond acceptors; Rbon, quantity of rotatable bonds; LogP: lipid-water partition coefficient.phytochemicals, which had been constant with RO5, in the followup research. The SwissTargetPrediction database (Daina et al., 2019) was utilised to study the possible targets with the 18 CR phytochemicals based on their structures, as well as a total of 376 prospective targets had been obtained. To supply insight into the biological functions of these 376 targets, we performed GO and KEGG pathway enrichment analyses employing the ClusterProfiler R package with all the adjusted value of p 0.05 (Yu et al., 2012). The GO terms incorporated BP, CC and MF. Evaluation of BP terms showed that many of the targets have been associated to peptidyl-tyrosine modification (GO:0018212), peptidyl-tyrosine phosphorylation (GO:0018108), response to lipopolysaccharide (LPS) (GO:0032496), G protein-coupled receptor signaling pathway (GO:0007187), cellular calcium ion homeostasis (GO:0006874) and so on. It truly is noteworthy that a lot of the CR targets had been primarily localized in synaptic membranes, such as integral component of synaptic membrane (GO: 0099699), intrinsic component of synaptic membrane (GO: 0099240), integral ERRĪ± medchemexpress element of presynaptic membrane (GO: 0099056) and membrane region (GO:0098589). The top 10 enriched cell elements had been related with 70 CR targets, which formed a PPI network with 69 nodes and 397 edges (Supplementary Figure S1A). Amongst these targets, amyloid precursor protein (APP), GRM5, SRC, GABBR1, GRM1, CNR1, HTR2A, CTNNB1, ALK1 manufacturer epidermal growth factor receptor (EGFR), and FYN have significant roles within the PPI network (Supplementary Figure S1B). KEGG pathway analysis revealed that these targets have been enriched in several synapse associated KEGG pathways (Supplementary Figure S1C). In line with evaluation of MF terms, CR associated targets are mainly involved in neurotransmitter receptor activity (GO: 0030594), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), G protein-coupled amine receptor activity (GO: 0008227), and transmembrane receptor protein kinase activity (GO:0019199) (Figure 2A). These data indicate that CR exerts protective effects on synaptic structure and synaptic function by