Structures and In Vitro Antihepatic Fibrosis Activities of Prenylated Dihydrostilbenes and Flavonoids from Glycyrrhiza uralensis Leaves

Abstract

Glycyrrhiza uralensis is the major plant source of licorice. This study was to identify bioactive compounds from the plant's leaves in order to make better use of its aerial part. An ethanol extract of the leaves was subjected to repeated chromatography to yield 15 compounds. The structures were determined to be three novel dihydrostilbenes, based on their various spectroscopic data-glycypytilbene A (1), glycydipytilbene (2), and glycypytilbene B (3)-and 12 known compounds, α,α -dihydro-3,5,4 -trihydroxy-4,3 -diisopentenylstilbene (4), α,α -dihydro-3,5,3 ,4 -tetrahydroxy-2,5 -diisopentenylstilbene (5), 6-prenyleriodictyol (6), 5 -prenyleriodictyol (7), 6-prenylquercetin-3-Me ether (8), 5prenylquercetin (9), 6-prenylquercetin (10), 6-prenylnaringenin (11), 3 -prenylnaringenin (12), sigmoidin C (13), 8-[(E)-3-hydroxymethyl-2-butenyl]-eriodictyol (14), and quercetin-3-Me ether (15). Most of these chemical constituents inhibited α-glucosidase activity, with the two prenylated quercetin derivatives (9 to 10) being the greatest active (IC 50 < 4.0 µg/mL) . Compounds 1, 3 to 4, 6 to 7, 9 to 12 impeded the growth of human hepatic stellate cells, with the prenylated flavonoids (6 to 7, 9 to 12) being more robust than their unprenylated counterparts.Practical Applications: This study found that Glycyrrhiza uralensis leaves contain prenylated dihydrostilbenes and flavonoids with inhibiting effects on α-glucosidase and on the proliferation of human hepatic stellate cells, which should prompt the development of G. uralensis leaves for healthy products with anti-diabetic or liver fibrosis-preventing effects.

Microbial Transformation of Prenylquercetins by Mucor hiemalis

“…Compound 6 showed the [M + H] + peak at m/z 533.1656 (calcd for C 26 H 29 O 12 , 533.1659), which established a molecular formula of C 26 H 28 O 12 , indicating that it was a glycosylated derivative of 2. Presence of the sugar moiety was confirmed by the additional proton and carbon signals (δ H 5.02 and 3.19-3.68 (6H); δ C 100.3, 77.5, 76.8, 73.5, 69.9, 61.0) observed in the 1 H and13 C NMR of 6. The sugar was assigned to be a glucopyranose on the basis of NMR data and by comparison of the TLC R f value with that of the d-glucose reference standard after acidic hydrolysis of 6.…”

“…Thus, metabolite 5 was assigned as 8-prenylquercetin 3-O-β-d-glucopyranoside. 13 C NMR of 6. The sugar was assigned to be a glucopyranose on the basis of NMR data and by comparison of the TLC R f value with that of the d-glucose reference standard after acidic hydrolysis of 6.…”

“…The 1 H and 13 C NMR spectra were obtained in DMSO-d 6 on a Bruker Avance III HD 400 spectrometer at 400 and 100 MHz, respectively, using TMS as internal standard. The chemical shift values (δ) are reported in ppm units, and the coupling constants (J) are in Hertz (Hz).…”

“…For example, 8-prenylquercetin (8-PQ) showed higher cellular uptake and lower efflux than quercetin in Caco-2 and C2C12 myotube cells and enhanced the bioavailability of quercetin in different tissues in vivo [10]. 5 -Prenylquercetin (uralenol) exhibited higher inhibitory effects against tyrosinase, PTP1B and α-glucosidase enzymes, and the growth of hepatic stellate cells compared with those of quercetin [11][12][13]. The notion that the biological activities of quercetin were enhanced by prenylation led to the synthesis of 8-PQ (1) and other derivatives.…”

Glycyrrhiza Genus: Enlightening Phytochemical Components for Pharmacological and Health‐Promoting Abilities

“…against the gastric adenocarcinoma (SGC-7901) cell line with IC 50 values in the range of 8.7 to 64.9 μ g/mL for different compounds. Moreover, Fan et al [ 125 ] identified the biologically active components of Glycyrrhiza uralensis Fisch. leaves and noted that most of these compounds exhibited an antiproliferative effect on human hepatic stellate cells with IC 50 values in the range of 43 to more than 90 μ g/mL for different compounds.…”