Additionally, the intestinal concentrations of VIP, SS, and ET-1 in model mice were significantly increased after the loperamide challenge (p < 0.05) (Figure 4D–F), suggesting that loperamide-induced constipation may also be associated with abnormalities in intestinal SP, MTL, GAS, VIP, SS, and ET-1 concentrations. Here, EDN1 is linked to constipation disorder.