Glycyrrhiza is a significant resource in both traditional Chinese medicine (TCM) and functional foods. Liquiritin, a flavonoid glycoside derived from the roots of Glycyrrhiza species, exhibits a broad spectrum of pharmacological activities. This review systematically summarizes recent research progress on liquiritin concerning its antioxidative, anti-inflammatory, antitumor, cardioprotective, neuroprotective, and metabolic regulatory effects. Current evidence is primarily derived from in vitro cellular assays and in vivo animal models, with no clinical studies reported to date. Available data indicate that antioxidative and anti-inflammatory activities constitute the core pharmacological foundation of liquiritin. By activating the Nrf2/Keap1 pathway and inhibiting NF-κB/MAPK signaling, among other mechanisms, liquiritin exerts synergistic protective effects across multiple organ systems. In the cardiovascular system, liquiritin alleviates arrhythmia, myocardial hypertrophy, and myocardial infarction. With respect to its antitumor properties, liquiritin demonstrates broad-spectrum activity through the regulation of cell cycle progression, induction of apoptosis, inhibition of metastasis, and reversal of drug resistance. In the nervous system, liquiritin promotes neurogenesis, modulates neurotransmitter metabolism, and suppresses neuroinflammation, thereby ameliorating pathological conditions associated with depression, Alzheimer's disease, and Parkinson's disease.Beyond this descriptive synthesis, a hierarchical framework linking antioxidant, anti-inflammatory, and anti-apoptotic mechanisms is proposed, and unresolved discrepancies in the literature are discussed. A comparative analysis with other flavonoid glycosides highlights distinguishing features of liquiritin, including its C-4′ glucosyl moiety, ERβ selectivity, and dual TRPV1/TRPA1 inhibition. However, several challenges remain, including low oral bioavailability (AUC of the parent compound is only 1.30 h·μg/mL following oral gavage in rats), a lack of long-term toxicity data, and a severe paucity of clinical investigations. Future research should prioritize disease-specific clinical trials and multi-omics mechanistic studies to facilitate the clinical translation of liquiritin. In summary, this review moves beyond previous descriptive accounts to provide a critically evaluative framework for liquiritin research. • Liquiritin shows promise for treating cardiovascular, nervous, and metabolic diseases. • Liquiritin's efficacy is broadly based on its antioxidant and anti-inflammatory activities. • Liquiritin modulates key pathways like Nrf2/Keap1, NF-κB/MAPK, and p53/caspase. • Liquiritin combats cancer by inducing apoptosis, inhibiting angiogenesis, and modulating tumor immunity.
Gao et al. (Thu,) studied this question.