Therapeutic effect of Cistanche deserticola on defecation in senile constipation rat model through stem cell factor/C-kit signaling pathway

BACKGROUND: Constipation is one of the chronic gastrointestinal functional diseases. It seriously affects the quality of life. Cistanche deserticola (C. deserticola) can treat constipation obviously, but its mechanism has not been clarified. We supposed that mechanism of it improved the intestinal motility by stimulating interstitial Cajal cells (ICC). Activation of the C-kit receptor on the surface of ICC is closely related to ICC function, and the stem cell factor (SCF)/C-kit signaling pathways plays an important role on it. To investigate the mechanism of how C. deserticola treats constipation, this study aimed to establish a constipation model in rats and explore the role of SCF/C-kit signaling pathway in the treatment. AIM: To explore the SCF/C-kit signaling pathways in the role of C. deserticola for treatment of constipation by a constipation rat model. METHODS: Forty-eight 8-mo-old Sprague–Dawley rats were divided into 4 groups by random weight method: Normal group (n = 12), model group (n = 12), C. deserticola group (n = 12) and blocker group (n = 12). The normal group received normal saline by gavage; the model group received loperamide by gavage; the blocker group received loperamide and C. deserticola by gavage, and STI571 was injected by intraperitoneally. During treatment, the weight, fecal granules and fecal quality were recorded every 10 d. On day 20 after model induction, the colon tissues of each group were removed. Hematoxylin and eosin staining was used to observe pathological changes. Expression levels of SCF, C-kit and Aquaporin genes were detected by immunohistochemistry, western blotting, and real-time-quantitative polymerase chain reaction. The colonic epithelial mitochondria and goblet cells were observed by transmission electron microscopy. RESULTS: Compared with the normal group, as treatment progressed, the weight of rats in the model and blocker groups decreased significantly, the stool weight decreased, and the stool quality was dry (P < 0.05). C. deserticola reversed the decrease in body weight and stool weight and improved stool quality. Histopathological analysis indicated that the colonic mucosal epithelium in the model group was incomplete, and the arrangement of the glands was irregular or damaged. Treatment with C. deserticola improved the integrity and continuity of the epithelial cells and regular arrangement of the glands. The blocking agents inhibited the effects of C. deserticola Immunohistochemistry and real-time-quantitative polymerase chain reaction showed that expression of SCF and C-kit protein or genes in the colonic tissue of the model group was decreased (P < 0.05), while treatment with C. deserticola increased protein or gene expression (P < 0.05). Western blotting showed that expression of aquaporin APQ3 was increased, while the expression of Cx43 decreased in the model group. Treatment with C. deserticola inhibited expression of APQ3 and promoted expression of Cx43. Transmission electron microscopy showed that the mitochondria of the colonic epithelium in the model group were swollen and arranged disorderly, and microvilli were sparse. The condition was better in the C. deserticola group. Mice treated with STI571 blocker confirmed that blocking the SCF/C-kit pathway inhibited the improvement of constipation by C. deserticola. CONCLUSION: C. deserticola improved defecation in rats with constipation, and the SCF/C-kit signaling pathway, which is a key link of ICC function, played an important role of the treatment.