Differences in the Effectiveness of Uridine and Liriope platyphylla L. Between Complement Component 3 Deficiency- and Loperamide-Induced Constipation May Be Associated with the Alternative Regulation of the Cyclic Adenosine Monophosphate Downstream S

<b>Background/Objectives</b>: Constipation can be induced in animal models through various factors such as loperamide (Lop) or complement component 3 (C3) deficiency. The effectiveness of therapeutic agents in the clinical management of constipation has been primarily evaluated within only one model, but between-model comparisons have not been performed so far. Therefore, we investigated whether the effectiveness of the laxative drugs for the clinical management is related to etiological factors. <b>Methods</b>: The changes in the key parameters for defecation were compared between C3 knockout (KO) mice with C3-deficiency-induced constipation and ICR mice with Lop-induced constipation after the oral administration of Uridine (Urd) and aqueous extract of <i>Liriope platyphylla</i> L. (AELP). <b>Results</b>: Similar effectiveness of Urd and AELP were detected on the stool frequency, intestinal epithelial barrier structure, and mucin secretion in both models. However, other parameters (namely gastrointestinal (GI) transit, water retention, and enteric nervous system (ENS) structure and function) showed higher effectiveness in C3 KO mice than in the Lop-induced model. Only the effectiveness of the two therapeutic agents on the histological structure of the mid-colon was greater in the Lop-induced mice model compared to the C3 KO mice model. Furthermore, these differences in the therapeutic effectiveness of Urd and AELP were partially reflected in alterations in the cyclic adenosine monophosphate (cAMP) downstream signaling pathway. <b>Conclusions</b>: The results suggest that the therapeutic effectiveness of Urd and AELP is sensitive to C3-deficiency-induced constipation and these differences may be linked to the alternative regulation of the cAMP downstream signaling.