Liquiritigenin is a natural flavonoid compound derived from licorice (Glycyrrhiza) that selectively activates estrogen receptor β (ERβ), with a half-maximal effective concentration (EC50) of 36.5nM. Various biological activities of liquiritigenin, including anti-inflammatory [1, 2], antioxidant [3], anticancer [4], organ-protective [5], bone growth-promoting [6], anti-infection [7], and antithrombotic [8] effects have been validated in both cell and animal models. Liquiritigenin is primarily metabolized in the liver by CYP3A enzymes, with marked inter-individual differences [9].
In vitro，pre-incubation with liquiritigenin (3, 10 and 30μM) for 1 hour dose-dependently reduced the levels of the inflammatory cytokines TNF-α, IL-1β, and IL-6 in LPS-stimulated Raw264.7 cells, with the most significant inhibition observed at 30μM [1]. HT22 cells were pretreated with liquiritigenin (10, 25 and 50μM) for 12h and then stimulated with glutamate. This treatment dose‑dependently inhibited glutamate‑induced ROS elevation, decreasing from 4.69‑fold to 1.89‑fold at 50μM. Liquiritigenin also slightly reduced lipid peroxidation levels (from 1.60‑fold to 1.45‑fold) at 50μM [3]. Treatment with liquiritigenin for 24 h significantly inhibited the viability of colorectal cancer cells (IC₅₀ of 13.70μM for SW480 and 15.28μM for DLD1) with low toxicity to normal colonic epithelial NCM460 cells (IC₅₀ = 111.41μM) [4].
In vivo, oral administration of liquiritigenin to male SD rats (50mg/kg/day for 3 days) or intravenous injection (15mg/kg/day for 2 days) significantly attenuated carrageenan‑induced paw edema [1]. Pneumonia was induced in mice by lipopolysaccharide or Staphylococcus aureus. A mixture containing six components including liquiritigenin (12.4μg/mL), was administered at 0.3mL/day for 7 consecutive days, which markedly reduced both mRNA and protein levels of iNOS in lung tissue and alleviated pulmonary inflammation [2]. A CCl₄‑induced mouse model of liver fibrosis was established. Oral administration of liquiritigenin (10mg/kg/day for 4 weeks) significantly decreased hepatic hydroxyproline content and reduced collagen deposition. α‑SMA expression was also suppressed, which alleviated liver fibrosis [5].
References:
[1] Kim, Y.W., et al., Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and proinflammatory cytokines production. Br J Pharmacol, 2008. 154(1): p. 165-73.
[2] Jiang, X., et al., Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid. J Pharm Anal, 2022. 12(6): p. 839-851.
[3] Yang, E.J., G.H. Park, and K.S. Song, Neuroprotective effects of liquiritigenin isolated from licorice roots on glutamate-induced apoptosis in hippocampal neuronal cells. Neurotoxicology, 2013. 39: p. 114-23.
[4] Li, R., et al., Liquiritigenin targets transferrin receptor to potentiate ferroptosis sensitivity in colorectal cancer cells. Phytomedicine, 2026. 154: p. 158057.
[5] Geng, W., et al., Liquiritigenin suppresses the activation of hepatic stellate cells via targeting miR-181b/PTEN axis. Phytomedicine, 2020. 66: p. 153108.
[6] Qiu, Y., et al., Liquiritigenin promotes osteogenic differentiation and prevents bone loss via inducing auto-lysosomal degradation and inhibiting apoptosis. Genes Dis, 2023. 10(1): p. 284-300.
[7] Kumar, S., et al., Effect of liquiritigenin on chloroquine accumulation in digestive vacuole leading to apoptosis-like death of chloroquine-resistant P. falciparum. Phytomedicine, 2023. 114: p. 154738.
[8] Cheng, L., et al., Liquiritigenin attenuates thrombosis by inhibiting P2Y(12)R-mediated Src/PLCγ2 signaling and cytoplasmic Ca(2+) mobilization in platelets. Phytomedicine, 2025. 149: p. 157553.
[9] Tsukamoto, S., et al., CYP3A4 inhibitors isolated from Licorice. Biol Pharm Bull, 2005. 28(10): p. 2000-2.