Pharmacological mechanisms of quercetin in liver and intestinal diseases: a gut-liver axis perspective

Hepatic and gastrointestinal disorders share interconnected pathogenic mechanisms, yet their clinical management remains challenging. This has prompted interest in therapeutic approaches targeting the gut-liver axis. Quercetin, a natural flavonoid, has been studied in this context. To assess its pharmacological effects, we searched PubMed, Web of Science, EMBASE, and the Cochrane Library for literature published since 2000 on quercetin in hepatic and intestinal diseases. This review focuses on the gut-liver axis as a framework for understanding the pharmacological effects of quercetin. Mechanistically, quercetin modulates gut-liver communication by reshaping the gut microbiota, promoting short-chain fatty acid production, and modulating bile acid metabolism. In preclinical models, it has been reported to modulate FXR/TGR5 signaling and preserve intestinal barrier integrity, thereby reducing endotoxin translocation and systemic inflammation. These effects are associated with downstream modulation of oxidative, inflammatory, and apoptotic pathways, including NF-κB, PI3K/Akt, and Nrf2. Furthermore, preclinical evidence indicates that quercetin attenuates liver injury, MASLD/MASH, fibrosis, and hepatocellular carcinoma, and exerts protective effects in models of ulcerative colitis and colorectal cancer. However, most of this evidence comes from in vitro and animal studies, and clinical evidence remains limited. By focusing on gut-liver crosstalk, this review provides a framework for understanding the pharmacological effects of quercetin and identifies key gaps that need to be addressed before clinical translation can be considered.