Sinisan ameliorates colonic injury induced by water immersion restraint stress by enhancing intestinal barrier function and the gut microbiota structure.

CONTEXT: Sinisan (SNS) has been used to treat psychosomatic diseases of the digestive system. But little is known about how SNS affects water immersion restraint stress (WIRS). OBJECTIVE: To study the effects of SNS on colonic tissue injury in the WIRS model. MATERIALS AND METHODS: Forty-eight Kunming (KM) mice were randomized into 6 groups (n = 8): The control and WIRS groups receiving deionized water; the SNS low-dose (SL, 3.12 g/kg/d), SNS middle-dose (SM, 6.24 g/kg/d), SNS high-dose (SH, 12.48 g/kg/d), and diazepam (DZ, 5 mg/kg/d) groups; each with two daily administrations for 5 consecutive days. The 5 treatment groups were subjected to WIRS for 24 h on day 6. The effects of SNS on colon tissue injury caused by WIRS were assessed by changes in colon histology, inflammatory cytokines, brain-gut peptides, and tight junction (TJ) proteins levels. 16S rRNA gene sequencing was used to detect the regulation of the gut microbiota. RESULTS: SNS pretreatment significantly reduced TNF-α (0.75- to 0.81-fold), IL-6 (0.77-fold), and IFN-γ (0.69-fold) levels; and increased TJ proteins levels, such as ZO-1 (4.06- to 5.27-fold), claudin-1 (3.33- to 5.14-fold), and occludin (6.46- to 11.82-fold). However, there was no significant difference between the levels of substance P (SP) and vasoactive intestinal peptide (VIP) in the control and WIRS groups. SNS regulated the composition of gut microbiota in WIRS mice. CONCLUSION: The positive effects of SNS on WIRS could provide a theoretical basis to treat stress-related gastrointestinal disorders.