Screening for bioactive natural products from a 67-compound library of Glycyrrhiza inflata

Licorice shows a variety of pharmacological activities. This work aims to discover bioactive natural products from one botanical source of licorice, Glycyrrhiza inflata. A total of 67 free phenolics were isolated to form a compound library. Based on the bioactivities of licorice, these compounds were screened using cell- or enzyme-based bioassay methods. A total of 11 compounds exhibited potent cytotoxic activities against three human cancer cell lines (HepG2, SW480 and MCF7), while showed little toxicity on human normal cell lines LO2 and HEK293T. A number of chalcones showed remarkable anti-inflammatory activities. Among them, 2 (licochalcone B, IC₅₀ 8.78μM), 10 (licoagrochalcone C, IC₅₀ 9.35μM) and 13 (licochalcone E, IC₅₀ 9.09μM) exhibited the most potent inhibitory activities on LPS-induced NO production, whereas 1, 8, 10, 12 and 13 (IC₅₀ 13.9, 7.27, 2.44, 6.67 and 3.83μM) showed potent inhibitory activities on NF-κB transcription. Nine prenylated phenolics were found to be PTP1B inhibitors. Particularly, licoagrochalcone A (4), kanzonol C (7), 2'-hydroxyisolupalbigenin (35), gancaonin Q (45), glisoflavanone (50) and glabrol (53) showed IC₅₀ values of 0.31-0.97μM. Compounds 24 (semilicoisoflavone B, IC₅₀ 0.25μM), 26 (allolicoisoflavone B, IC₅₀ 0.80μM) and 64 (glabridin, IC₅₀ 0.10μM) showed noticeable tyrosinase inhibitory activities. Most of the above bioactive compounds were reported for the first time.