A systematic review of polyphenols therapeutic and preventive role in cholelithiasis

Introduction: Gallstone disease (GSD) or cholelithiasis has become prevalent in recent years and can increase the risk of gallbladder cancers. This systematic review study investigates the effects of polyphenols in preventing and treating GSD and its associated complications. Methods: An extensive search of the available literature was performed for articles published since 5/20/2024 using multiple databases, including PubMed, Scopus, Web of Science, Embase, and Cochrane Library, using polyphenols, phenolic compounds, gallstones, and cholelithiasis-related keywords. After screening the records, data were extracted, and the most important outcomes were reviewed. Results: Polyphenols reduce the levels of ABCG5/8 in the liver and decrease the expression of Niemann-Pick C1-like 1 (NPC1L1) and sterol regulatory element-binding protein 2 (SREBP2) in the intestine. Additionally, the upregulation of the CYP7A1 gene may help regulate various genes, enzymes, and proteins, potentially leading to GSD. They also reduce the cholesterol saturation index (CSI), bile salts, phospholipids, lipid peroxidation, and malondialdehyde (MDA) levels. They also increase glutathione (GSH) levels and alleviate edema in the gallbladder wall. Additionally, polyphenols inhibit the action of 5-Lipoxygenase (a lipid mediator of inflammation), nuclear factor kappa B (NF-κB), peroxisome proliferator-activated receptor-γ (PPAR-γ), and cyclooxygenase-2 (COX-2). These actions contribute to their antioxidant and anti-inflammatory properties in relation to GSD. They also prevented GSD by modulating gut microbiota and improving histopathological changes. Conclusion: Polyphenols have potentially protective effects against GSD incidence. Further clinical studies are necessary before they can be used in clinical settings.