Spicatoside A in red Liriope platyphylla displays a laxative effect in a constipation rat model via regulating mAChRs and ER stress signaling

Red Liriope platyphylla extract (EtRLP) has been used as an oriental medicine for treatment of several chronic conditions, such as neurodegenerative disorders, diabetes, and obesity. To investigate the laxative activity of EtRLP, the levels of key constipation markers and their molecular regulators were examined following administration of EtRLP in constipation Sprague Dawley (SD) rats treated with loperamide (Lop). Compared with the Lop+Vehicle-treated group, the excretion levels of urine and stool were significantly enhanced in the Lop+EtRLP-treated group, even though feeding levels were kept constant. There was a significant improvement in histological structure, cytological ultrastructure and mucin secretion in transverse colon sections from the Lop+EtRLP-treated group, compared with the Lop+Vehicle-treated group. The Lop+EtRLP-treated group exhibited a rapid recovery of the muscarinic acetylcholine receptor (mAChR) signaling pathway and of the endoplasmic reticulum (ER) stress response, compared with Lop+Vehicle-treated group. Spicatoside A, one of the key components detected in EtRLP, recovered the levels of inositol triphosphate (IP3) and Gα in primary rat intestinal smooth muscle cells (pRISMCs). Taken together, the present results indicated that spicatoside A-containing EtRLP had therapeutic effects against Lop-induced constipation in SD rats via improvement of the mAChR downstream signaling pathway and the ER stress response.