Isoliquiritigenin

Isoliquiritigenin is a flavonoid that is found in Glycyrrhizae species and has diverse biological activities including anticancer, anti-steatotic, antioxidant, anti-inflammatory, gastroprotective, and estrogenic properties.^1,2,3,4,5 It reduces tumor growth in an NCI-H1975 non-small cell lung cancer (NSCLC) mouse xenograft model when administered at doses of 1 and 5 mg/kg.¹ Isoliquiritigenin (10 mg/kg per day) inhibits hepatic steatosis, as indicated by reduced hepatic fat and triglyceride accumulation, and increases in hepatic thiobarbituric acid-reactive substances (TBARS), inducible nitric oxide synthase (iNOS), and COX-2 levels in mice fed a high-fat diet.⁴ It also inhibits LPS-induced increases in IL-1β and IL-6 levels in J774A.1 murine macrophages (IC₅₀s = 7.2 and 7.16 μM, respectively).² Isoliquiritigenin (5 and 10 mg/kg) reduces gastric acid secretion and gastric ulcer formation in pylorus-ligated rats.³ It is an estrogen receptor α (ERα) and ERβ agonist (IC₅₀s = 16 and 7.8 μM, respectively) and induces estrogen-responsive alkaline phosphatase activity in Ishikawa endometrial cancer cells (EC₅₀ = 2.7 μM).⁵ Isoliquiritigenin is also a histamine H₂ receptor and liver X receptor α (LXRα) antagonist.^3,4

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1. Jung, S.K., Lee, M.-H., Lim, D.Y., et al. Isoliquiritigenin induces apoptosis and inhibits xenograft tumor growth of human lung cancer cells by targeting both wild type and L858R/T790M mutant EGFR. The Journal of Biological Chemisty 289(52), 35839-35848 (2014).

2. Thiyagarajan, P., Chandrasekaran, C.V., Deepak, H.B., et al. Modulation of lipopolysaccharide-induced pro-inflammatory mediators by an extract of Glycyrrhiza glabra and its phytoconstituents. Inflammopharmacology 19(4), 235-241 (2011).

3. Kim, D.C., Choi, S.-Y.S., Kim, S.H., et al. Isoliquiritigenin selectivity inhibits H2 histamine receptor signaling. Mol. Pharmacol. 70(2), 493-500 (2006).

4. Kim, Y.M., Kim, T.H., Kim, Y.W., et al. Inhibition of liver X receptor-α-dependent hepatic steatosis by isoliquiritigenin; a licorice antioxidant flavonoid, as mediated by JNK1 inhibition. Free Radic. Biol. Med. 49, 1722-1734 (2010).

5. Hajirahimkhan, A., Simmler, C., Yuan, Y., et al. Evaluation of estrogenic activity of licorice species in comparison with hops used in botanicals for menopausal symptoms. PLoS One 8(7), e67947 (2013).