centrality Figure calculated. In theof the KEGG pathway enrichmentindicates(A) Bubble diagram visualwere four. Bubble diagrams network analysis, the degree evaluation. the direct influence and izing KEGG pathway evaluation of hispidulin anti-obesity key targets. (B) Bubble diagram visualizing value of the node. Consequently, high degree nodes play BRaf Inhibitor Biological Activity crucial roles inside the network. KEGG pathway evaluation of p-synephrine anti-obesity key targets. As shown in Figure 5A, the hispidulin C network consisted of 31 nodes (1 compound node, 15 key target nodes, and 15 pathway nodes) and 74 edges. Among the three.1.4. Building and Analysis of Compound arget athway Networks essential target nodes, AKT1, SRC, EGFR, and GSK3B H2 Receptor Agonist Source showed high degree values of 15, 9, 9, and An integrative network analysis was performed employing Cytoscape to acquire a extra eight, respectively. Inside the pathway nodes, estrogen, prolactin, Rap1, and PI3K-Akt signaling extensive understanding of your compounds, chosen crucial targets, and pathways repathways exhibited the degree values of six, 5, five, and 5, respectively. lated for the two5B, the p-synephrine C network formed 1 compound node, 16represent In Figure drugs. The C networks are shown in Figure five. Blue squares essential target compounds, reddish circles represent crucial specific, ADRB1, ADRB2, GRIN1, and ADRB3 nodes, 12 pathway nodes, and 63 edges. In targets, and green diamonds represent pathways. The size and colour of of 9,circles indicate the degree of every target. Through the showed higher degree values the eight, 6, and six, respectively. amongst these, ADRB1, ADRB2, network analysis, the parameter degree, betweenness centrality, andanalysis. Additionally, and ADRB3 have been the essential targets that clustered inside the PPI network closeness centrality had been calculated. In connected to evaluation, theand cAMP signaling pathways, which hadimthese targets had been the network the calcium degree indicates the direct influence along with the portancedegree node. Hence, higher degree nodes play vital roles within the network. highest with the values among the pathway nodes.Biomolecules 2021, 11, x12 ofFigure five. Cont.Biomolecules 2021, 11,13 ofFigure five. Integrated compound arget athway (C ) networks. (A) C network of hispidulin. Figure five. Integrated compound arget athway (C ) networks. (A) C network of his(B) C network of p-synephrine. (C) Combination C network of hispidulin and p-synephrine. pidulin. (B) C network of p-synephrine. (C) Combination C network of hispidulin and psynephrine.The mixture C network consisted of 60 nodes (two compound nodes, 31 important target nodes, and 27 pathway nodes) and 137 edges, as shown in Figure 5C. As As shown in Figure 5A, the hispidulin C network consisted of 31 nodes (1 comshown within the combination network,and 15were no shared crucial targets or pathways amongst pound node, 15 key target nodes, there pathway nodes) and 74 edges. Among the important the predicted AKT1, SRC, EGFR, and GSK3B showed highsuggest values of 15, 9, 9,and ptarget nodes, crucial targets and pathways. These benefits degree that hispidulin and eight, synephrine may exhibit anti-obesity effects by means of distinctive mechanisms of action. respectively. In the pathway nodes, estrogen, prolactin, Rap1, and PI3K-Akt signaling pathways exhibited the degree values of six, five, 5, and five, respectively. 3.2. Inhibitory Effects of Hispidulin and p-Synephrine on Adipogenesis in 3T3-L1 Preadipocytes In Figure 5B, the p-synephrine C network formed 1 compound node, 16 key tarThe cytotoxicity of h