SAHA Alleviates Diarrhea-Predominant Irritable Bowel Syndrome Through Regulation of the p-STAT3/SERT/5-HT Signaling Pathway

Abstract

Objective Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and stool irregularity. However, its pathophysiological mechanisms, which trigger intestinal motility disorders and diarrhea leading to diarrhea-predominant IBS (D-IBS), remain largely unknown. Methods In the present study, we established a D-IBS rat model by mother–infant separation combined with restraint stress. Then we exposed the modelled rats to suberoylanilide hydroxamic acid (SAHA) treatment, followed by determination of their visceral sensitivity. Toluidine blue staining served to reveal the effects of SAHA treatment on mast cells of D-IBS model rats. Then we measured the expression of serotonin (5-hydroxytryptamine; 5-HT) and its receptors by ELISA. Results Construction of short hairpin RNA (sh)-serotonin transporter (SERT) lentivirus vectors verified the regulation of the 5-HT signaling pathway by phosphorylated (p)-STAT/SERT. SAHA treatment of D-IBS model rats reduced the fecal water content, electromyography integral change rate, abdominal withdrawal reflex score, and number of mast cells, as well as the expression of 5-HT type 3A (5-HT3AR), 3B receptor (5-HT3BR), and 4 receptor (5-HT4R) receptors. The treatment also elevated the expression of signal transducer and activator for transcription 3 (STAT3) and SERT. Activation of p-STAT3 may reverse the inhibitory effect of SAHA on the elevated visceral sensitivity of D-IBS model rats. Moreover, SAHA promoted the transcription of SERT through repression of the p-STAT3/5-HT signaling, thereby inhibiting the visceral sensitivity of D-IBS model rats. Conclusion This study highlights that SAHA treatment can alleviate D-IBS through regulation of the p-STAT3/SERT/5-HT signaling pathway.

Protective effect of Pediococcus pentosaceus Li05 on diarrhea-predominant irritable bowel syndrome in rats

“…Stressful life events can lead to various mental and gastrointestinal disorders, including IBS-D. Rat models such as restraint stress and maternal separation can cause visceral hypersensitivity, anxiety-like behavior, and abnormal intestinal motility and diarrhea, which are among the pathological and physiological mechanisms of IBS-D. 28,29 AWR is a reliable indicator for assessing visceral sensitivity in IBS-D. 30 Our results revealed that there was no statistically significant difference observed among the three groups at a pressure of 0.2 ml ( p > Food & Function Paper 0.05 for all pairwise comparisons). As the applied pressure increased, the AWR scores in the IBS-D group were significantly higher than that in the Ctrl group, while the AWR scores in the Li05 group exhibited a significant decrease compared the IBS-D group ( p < 0.05) (Fig.…”

Gallic Acid Alleviates Visceral Pain and Depression via Inhibition of P2X7 Receptor

“…Irritable bowel syndrome (IBS) is a gastrointestinal disorder that is characterized by altered defecation habits, abdominal discomfort, and abdominal pain. It is said that IBS affects the lives of 10–15% of the global population [ 1 ]. Since IBS is the most prevalent functional gastrointestinal disorder (FGID) in chronic visceral pain [ 2 , 3 , 4 , 5 ], we selected it as the investigatory target in this study representing chronic visceral pain.…”