Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced gastrointestinal dysfunction in Parkinson's disease mice

Figure 1 The network pharmacology analysis of rhapontin treatment of Parkinson's disease. A: The chemical structure of rhapontin; B: Venn diagram of overlapping targets associated with rhapontin in Parkinson's disease (PD); C: Protein-protein interaction of potential targets of rhapontin to treat PD. The deeper the color, the greater the degree. The line between two nodes represents the interaction; D: Gene ontology functional enrichment analysis. PD: Parkinson's disease; PPI: Protein-protein interaction; GO: Gene ontology; BP: Biological process; CC: Cell component; MF: Molecular function.

Figure 2 Rhapontin ameliorates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced motor and gastrointestinal dysfunction of Parkinson's disease mice. A: Representative traces of the open field test; B: Distance of the open field test; C: Time to descend of pole test; D: Fecal pellets of each group at 15 minutes; E: Fecal moisture percentage of each group; n = 10. ^aP < 0.05; ^bP < 0.01; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M: MPTP; R: Rhapontin; ML: ML385.

Figure 3 Rhapontin ameliorates dopaminergic neuronal damage of Parkinson's disease mice. A: Representative immunofluorescence images of TH-positive cells in the substantia nigra; B: Representative immunofluorescence images of TH-positive cells in the striatum; C: Quantification analysis of TH-positive cell number in Substantia nigra and Striatum. n = 10. ^aP < 0.05; ^bP < 0.01; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M: MPTP; R: Rhapontin; ML: ML385.

Figure 4 Rhapontin ameliorates inflammation of Parkinson's disease mice. A: Quantification analysis of pro-inflammatory cytokines [Interleukin (IL)-6, tumor necrosis factor-α, and IL-1β] and anti-inflammatory cytokines (IL-10) in the substantia nigra; B: Quantification analysis of pro-inflammatory cytokines and anti-inflammatory cytokines in the striatum; C: Quantification analysis of pro-inflammatory cytokines and anti-inflammatory cytokines in the colon; n = 10. ^aP < 0.05; ^bP < 0.01; NS: Not significant; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; IL: Interleukin; TNF-α: Tumor necrosis factor-α; M: MPTP; R: Rhapontin; ML: ML385.

Figure 5 Rhapontin activates nuclear factor erythroid 2-related factor 2 in the colon. A: Western Blot image and analysis of nuclear factor erythroid 2-related factor 2 (NRF2) in colon; B: Western blot image and analysis of NRF2 in substantia nigra; C: Western blot image and analysis of NRF2 in striatum. n = 10. ^aP < 0.05; ^bP < 0.01; NS: Not significant; NRF2: Nuclear factor erythroid 2-related factor 2; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; M: MPTP; R: Rhapontin; ML: ML385.