Pharmacological Effects of Licorice (Glycyrrhiza spp.) and Its Bioactive Constituents: The Perspective of Intestinal Microbiota.

Licorice (Glycyrrhiza spp.) is a traditional medicinal plant whose roots and rhizomes possess multiple pharmacological effects. Its core active components include flavonoids, triterpenoids such as glycyrrhizin, and polysaccharides. This paper focuses on licorice's gut microbiota-mediated mechanisms of action. Licorice enhances intestinal barrier integrity and protects gastrointestinal mucosa by upregulating tight junction proteins, activating repair pathways like epidermal growth factor receptor/extracellular regulated protein kinases (EGFR/ERK), and modulating inflammatory signaling via the tumor necrosis factor/nuclear factor-κB (TNF/NF-κB) pathway. At the systemic level, licorice modulates core pathways like Toll-like receptor 4 (TLR4)/NF-κB and farnesoid X receptor/Takeda G protein-coupled receptor 5 (FXR/TGR5) through cross-organ axes such as the gut-immune, gut-liver, and gut-adipose axes to improve conditions including inflammatory bowel disease (IBD), obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD). However, licorice poses dose-dependent risks which raise concerns regarding its safety. Long-term high-dose use may induce pseudohyperaldosteronism and interactions with multiple medications, and thus necessitates strict clinical dose control. This study reveals the gut microbiota's central mediating role in licorice's efficacy, and thereby provides theoretical support for its rational clinical application.