Licorice Water Extract Improves Constipation by Repairing the Intestinal Barrier and Regulating the Gut Microbiota: A Potential Alternative Treatment Strategy

Constipation is a prevalent intestinal disorder that significantly diminishes patients' quality of life and predisposes them to various serious health conditions. Current therapeutic approaches for constipation frequently result in drug dependence and adverse effects. In this study, we present evidence that licorice water extract (LWE), a naturally derived compound from Glycyrrhiza uralensis Fisch, effectively ameliorates constipation in mice induced by diphenoxylate (DIP). Our findings indicate that oral administration of LWE (82 mg/kg/d) substantially reduces defecation time, enhances intestinal motility, and increases fecal water content in constipated mice. Furthermore, LWE elevates the levels of excitatory neurotransmitters such as serotonin (5-HT) and motilin (MTL), while concurrently decreasing the levels of inhibitory neurotransmitters including vasoactive intestinal peptide (VIP), nitric oxide (NO) as well as Lipopolysaccharide (LPS). Mechanistically, compared to the model control group, the LWE treatment upregulates the expression of ZO-1, Occludin , and MUC2 genes; repairs DIP-induced damage to the intestinal barrier; increases aquaporin 3 ( AQP3 ) protein expression; downregulates Toll-like receptor 4 ( TLR4 ); mitigates low-grade intestinal inflammation; and restores colonic goblet cell populations. Additionally, LWE is metabolized by gut microbiota, thereby restoring dysbiosis associated with DIP-induced constipation. In conclusion, our results suggest that LWE alleviates constipation through mechanisms involving intestinal barrier repair and gut microbiota modulation, highlighting its potential as an alternative therapeutic option for this condition. In response to this, we have developed a convenient gel-type candy (LWEI) with licorice extract and inulin as the main ingredients, which has shown good efficacy in relieving constipation.