esity targets of hispidu 3 P00533 EGFR 10 0.126 0.778 four P10275 AR 6 0.047 0.636 mainly associated to estrogen, prolactin, CEGF, and Rap1 signaling pathways. In 5 P03372 ESR1 six 0.025 0.636 lar, the estrogen signaling pathway exhibited the highest p-value. For p-synephr 6 P14780 MMP9 5 0.025 0.609 pathways, the calcium signaling pathway and the cAMP signaling pathway, show 7 P18031 PTPN1 5 0.017 0.609 IGF1R five 0.008 0.609 higher eight CXCR4 Inhibitor list p-values. P08069 9 10 11 12 13 14 15 P35354 Q92731 P05067 P49841 P35228 P35968 P35869 PTGS2 ESR2 APP GSK3B NOS2 KDR AHR four four three 3 3 three 3 0.007 0.000 0.010 0.007 0.004 0.003 0.002 0.560 0.583 0.560 0.538 0.560 0.538 0.Table four. Hispidulin anti-obesity crucial targets identified according to PPI network topological evaluation. No. 1 two 3 four 5 6 7 8 Uniprot ID P14416 P23975 P31645 P46098 Q05586 P08908 P28223 Q13224 Gene DRD2 SLC6A3 SLC6A4 HTR3A GRIN1 HTR1A HTR2A GRIN2B Degree five 5 five five 4 four four 3 Betweenness Centrality 0.256 0.211 0.120 0.159 0.188 0.053 0.053 0.006 Closeness Centrality 0.647 0.611 0.611 0.611 0.550 0.579 0.579 0.Biomolecules 2021, 11,11 ofFigure three. Protein rotein interaction network of potential anti-obesity target genes of p-synephrine. The size Cont. red hue of a node represent its significance inside the network. Table four. andBetweenness Closeness 3.1.three. KEGG Pathway Enrichment Analysis Degree No. Uniprot ID Gene Centrality Centrality The DAVID database wasADRB2 to recognize signaling pathways related using the applied 9 CYP1 Inhibitor Purity & Documentation P07550 3 0.667 1.000 crucial targets of hispidulin and p-synephrine. The results in the biological pathways are ten P21917 DRD4 three 0.029 0.458 P08913 SLC6A2 3 0.017 shown11 Figure four. As shown in Figure 4A, the important anti-obesity targets of0.500 in hispidulin had been 12 related to estrogen, prolactin, CEGF, two P13945 ADRB3 0.000 0.750 In particuprimarily and Rap1 signaling pathways. 13 P08588 ADRB1 2 0.000 0.750 lar, the estrogen signaling pathway exhibited the highest p-value. For p-synephrine, two 14 P35462 DRD3 two 0.000 0.423 pathways, the calcium signaling pathway and the cAMP signaling pathway, showed quite 15 P35368 ADRA1B 1 0.000 0.600 16 P35372 OPRM1 1 0.000 0.367 higher p-values.Biomolecules 2021, 11, x11 ofFigure four. Bubble diagrams of KEGG pathway enrichment evaluation. (A) Bubble Bubble diagram Figure 4. Bubble diagrams of thethe KEGG pathway enrichment analysis. (A)diagram visualiz- visualing KEGG pathway analysis of hispidulin anti-obesity important targets. (B) Bubble diagram visualizing izing KEGG pathway analysis of hispidulin anti-obesity essential targets. (B) Bubble diagram visualizing KEGG pathway analysis p-synephrine anti-obesity key targets. KEGG pathway evaluation of of p-synephrine anti-obesity key targets.three.1.4. Construction and Analysis of Compound arget athway NetworksAn integrative network analysis was performed working with Cytoscape to obtain a extra complete understanding from the compounds, selected crucial targets, and pathways re-Biomolecules 2021, 11,12 of3.1.4. Construction and Evaluation of Compound arget athway Networks An integrative network evaluation was performed utilizing Cytoscape to acquire a extra extensive understanding in the compounds, chosen essential targets, and pathways associated for the two drugs. The C networks are shown in Figure 5. Blue squares represent compounds, reddish circles represent essential targets, and green diamonds represent pathways. The size and color with the circles indicate the degree of each target. Via the network analysis, the parameter degree, betweenness centrality, and closeness
