Gastrodin alleviates loperamide-induced slow transit constipation in mice by modulating the MAPK signaling pathway.

Abstract

BACKGROUND: Slow transit constipation (STC) is a prevalent functional gastrointestinal disorder. Gastrodin (GAS), a natural compound, has demonstrated protective effects in intestinal contexts; however, its therapeutic potential and mechanisms of action in STC remain largely unexplored. METHODS: A total of 30 male C57BL/6 mice (6 weeks old) were used in this study. An STC model was established using loperamide. The therapeutic effects of GAS were systematically evaluated by measuring several parameters: stool output (fecal pellet count and moisture content), intestinal transit rate, and colon histopathology. Furthermore, we analyzed serum and colonic levels of inflammatory cytokines, key neurotransmitters, and aquaporins (AQPs). The integrity of interstitial cells of Cajal (ICC) in the colon was assessed via immunohistochemistry. Finally, the expression levels of proteins associated with the mitogen-activated protein kinase (MAPK) signaling pathway were examined. RESULTS: GAS administration significantly improved STC symptoms by promoting defecation, enhancing gastrointestinal motility, and ameliorating histopathological damage in the colon. It also markedly attenuated intestinal inflammation, normalized the expression of neurotransmitters and AQPs, and restored the loperamide-induced depletion of ICC networks. Mechanistically, the protective effects of GAS were associated with the suppression of the MAPK signaling pathway, as evidenced by reduced phosphorylation of its key components: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. CONCLUSION: Our findings indicate that GAS possesses significant therapeutic potential for STC by mediating its beneficial effects through the regulation of intestinal inflammation, motility, and water transport, ultimately via the inhibition of the MAPK signaling pathway.