Shengxue Tongbian granules alleviate loperamide-induced slow transit constipation in mice through modulation of ER stress and apoptosis.

Slow transit constipation (STC) is a chronic gastrointestinal disorder marked by impaired intestinal motility and reduced frequency of bowel movements, often linked to the dysfunction of interstitial cells of Cajal (ICC). Endoplasmic reticulum (ER) stress and subsequent apoptosis in ICC play a pivotal role in the pathogenesis of STC. Shengxue Tongbian Granules, a Traditional Chinese Medicine formulation, have shown potential in treating constipation, though their mechanisms remain unclear. This study investigates the effects of Shengxue Tongbian Granules in a loperamide-induced STC mouse model. Mice were treated with varying doses of Shengxue Tongbian Granules and assessed for fecal output, intestinal motility, and histopathological changes. Results indicated a significant improvement in fecal output, water content, and intestinal propulsion in Shengxue Tongbian Granules-treated mice compared to controls. Furthermore, Shengxue Tongbian Granules alleviated histopathological damage in the colon, preserved ICC levels, and reduced ER stress-mediated apoptosis by modulating key markers, including p-PERK, p-eIF2α, IRE1α, ATF6, GRP78, CHOP, cleaved caspase-3, and calreticulin. The protective effects of Shengxue Tongbian Granules were further confirmed through siRNA-mediated calreticulin knockdown in ICC, which abolished the anti-apoptotic benefits of the treatment. These findings suggest that Shengxue Tongbian Granules exert therapeutic effects in STC by improving gut motility, preserving ICC function, and mitigating ER stress-mediated apoptosis, offering a potential alternative for managing STC.