Improving intestinal health and mitigating Loperamide-Induced constipation through the modulation of Aquaporin-3 expression, reduction of oxidative stress, and suppression of inflammatory response by fermented rice extract

• Effects of FRE on Small Intestinal Transit Parameters in a Loperamide-Induced Constipation Rat Model. • Effects of FRE Administration on Colonic Histomorphology Changes and Mucin expression of Loperamide-Induced Constipated Rats. • Improvement of Intestinal Tissue Dysfunction in Constipated Rats upon FRE Administration. • Anti-Inflammatory and Antioxidant Effects of FRE in Constipated Rats. • FRE modulating mitogen-activated protein kinases (MAPKs) phosphorylation. Constipation, a prevalent gastrointestinal disorder characterized by infrequent bowel movements and associated abdominal discomfort, poses a significant health concern. This study aimed to investigate the pharmacological impact and molecular mechanism of fermented rice extract (FRE). FRE significantly increased fecal number, fecal water content and gastrointestinal transit rate in loperamide-mediated rats. Abnormalities in morphology of colon tissues, along with alterations in antioxidant contents were markedly reversed by FRE. Furthermore, the treatment of constipated rats with FRE accelerated intestinal motility, fortified gut barrier protection, and improved water and salt metabolism in the intestinal tract. Additionally, FRE robustly attenuated inflammation expression, along with suppressing MAPKs phosphorylation in colon tissues of rats. In conclusion, FRE treatment alleviated loperamide-induced constipation by reducing intestinal transit time, modulating oxidative stress and mitigating inflammatory responses. This study underscores FRE as a promising candidate for the management of constipation, emphasizing its potential in regulating oxidative stress, and inflammatory pathways.