Liquiritigenin, a flavanone isolated from Glycyrrhiza uralensis, is a highly selective estrogen receptor β (ERβ) agonist with an EC50 of 36.5 nM for activation of the ERE tk-Luc.
Liquiritigenin produces a dose-response activation of ERE tk-Luc in the U2OS cells transfected with ERβ, but not ERα. Liquiritigenin produces a dose-dependent activation and a time-dependent increase of the CECR6, NKG2E and NKD with ERβ but not with ERα. The ERβ-selectivity of liquiritigenin is due to the selective recruitment of the coactivator steroid receptor coactivator-2 to target genes. Liquiritigenin exhibits similar binding affinities for ERα and ERβ, and causes the recruitment of SRC-2 to target genes selectively in ERβ cells[1]. Pretreatment of MC3T3-E1 cells with liquiritigenin prevents the MG-induced cell death and production of protein adduct, intracellular reactive oxygen species, mitochondrial superoxide, cardiolipin peroxidation, and TNF-α in osteoblastic MC3T3-E1 cells[2].
In a mouse xenograph model, liquiritigenin does not stimulate uterine size or tumorigenesis of MCF-7 breast cancer cells[1]. Treatment with liquiritigenin significantly reduces the concentrations of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in serum and hippocampus[3].
References:
[1]. Mersereau JE, et al. Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist. Mol Cell Endocrinol. 2008 Feb 13;283(1-2):49-57.
[2]. Suh KS, et al. Protective effect of liquiritigenin against methylglyoxal cytotoxicity in osteoblastic MC3T3-E1 cells. Food Funct. 2014 Jul 25;5(7):1432-40.
[3]. Tao W, et al. Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway. Behav Brain Res. 2016 Jul 15;308:177-86.