After the loperamide challenge, the serum concentrations of SP, MTL, and GAS were significantly reduced in model mice compared to the normal group (p < 0.05) (Figure 3A–C); and the concentrations of VIP, SS, and ET-1 were significantly increased in model mice relative to the control group (p < 0.05) (Figure 3D–F), suggesting that loperamide-induced constipation may also be associated with abnormalities in serum SP, MTL, GAS, VIP, SS, and ET-1 concentrations. Here, EDN1 is linked to Constipation.