Comparative evaluation of two herbal formulas for gastrointestinal function and gut microbiota modulation in rats with loperamide-induced dyspepsia

Dyspepsia is a prevalent refractory condition that arises from various causes and lacks definitive treatment. There is an urgent need for evidence to support the use of herbal medicines in the treatment of gastroenterological disorders. This study aimed to compare the therapeutic effects of two common herbal formulas-namely, Shihosogan-tang (SST) and Yijung-tang (YJT)-on loperamide (LOP)-induced dyspepsia and to explore their potential mechanisms. A dyspepsia model was established using Sprague-Dawley rats by intraperitoneal LOP injection at a dose of 3 mg/kg/day for one week. During this period, 30% ethanol extract of SST (1.4 g/kg/day) or YJT (2 g/kg/day) was intragastrically administered in rats. Mosapride (3 mg/kg/day) was used as the positive control. Unlike YJT, SST significantly mitigated LOP-induced reductions in intestinal length, gastrointestinal transit ratio, and serum ghrelin levels. Conversely, YJT significantly enhanced defecation, ileum villus length, and muscular thickness, outperforming SST. Expression of genes related to intestinal motility (ZO-1), inflammation (IL-6), and water absorption (SERT, AQP-3) indicated that both treatments ameliorated LOP-induced changes in the duodenum. Additionally, neuropeptides and hormones (TRH, bombesin, motilin, glucagon, neurotensin, PYY), Toll-like receptors (TLR-2 and TLR-4), and growth factors (GDNF and BMP2) were noticeably altered by SST and/or YJT treatment. While neither LOP nor the herbal formulas affected gut microbiota α-diversity, SST and YJT altered β-diversity compared to LOP alone, unlike mosapride. SST improves dyspepsia more effectively than YJT, possibly through mechanisms involving intestinal hormone regulation, inflammation inhibition, and gut microbiota modulation.