To exploit Glycyrrhiza uralensis resources, we examined the bioactive constituents of G. uralensis leaves. Seven chemical components were isolated by repeat column chromatography, and using spectroscopic methods, their structures were determined to be a novel prenylated dihydrostilbene, α,α′-dihydro-3,5,3′,4′-tetrahydroxy-2,5′-diprenylstilbene (1); a methylated flavonoid, quercetin-3-Me ether (4); and 5 prenylated flavonoids: 5′-prenylquercetin (3), 8-[(E)-3-hydroxymethyl-2-butenyl]eriodictyol (7), 6-prenyleriodictyol (5), 5′-prenyleriodictyol (6), and 6-prenylquercetin-3-Me ether (2). Compounds 1–7 and their unprenylated counterparts, glycosides, and other related compounds (8–13) were quantitatively analyzed. Using a macroporous resin column, most of these compounds could be enriched in the 40% to 60% ethanol-eluted fractions. Compounds 1–7 showed strong radical scavenging activity toward DPPH, and most of them demonstrated greater inhibitory activity against α-glucosidase than their unprenylated counterparts.Keywords: chemical constituents; Glycyrrhiza; leaves of Glycyrrhiza uralensis; prenylated flavonoids; α,α′-dihydro-3,5,3′,4′-tetrahydroxy-2,5′-diprenylstilbene;

•Acetylated or acetone-conjugated flavan-3-ols were prepared.•The 3, 5 or 3, 7-O-diacetyl flavan-3-ols have high cell penetration ability.•The diacetyl flavan-3-ols released free flavan-3-ols in cells.•Acetone conjugates of flavan-3-ols entered into cells in intact form.•The derivatives protected oxidative hemolysis more effectively than flavan-3-ols.Catechin and epicatechin are the health beneficial flavan-3-ols in tea and many fruits. However, their extreme hydrophilicity renders drawbacks for them to pass through the bio-membranes. We prepared lipophilic flavan-3-ol derivatives by acetylation or by acetone-conjugation. The structures of these derivatives were determined based on their NMR and MS spectra. The 3,5- and 3,7-diacetyl derivatives showed radical scavenging activity slightly weaker than catechin and epicatechin, but showed significantly enhanced capacity to penetrate into living cells. Moreover, the diacetyl derivatives released flavan-3-ols inside cells, while catechin or epicatechin themselves could not penetrate into the cells. The acetone conjugates showed strong antioxidant activity and were able to enter into living cells in the intact form. The acetylated and acetone-conjugated derivatives protected H2O2-induced erythrocyte hemolysis more effectively than catechin and epicatechin. These results indicated that acetylated and acetone-conjugated flavan-3-ols are promising compounds with less hydrophilicity and better bioactivities in biological systems.

Highlights•Conjugates of flavan-3-ols with cysteine or acetylcysteine were prepared.•The preparation was simple, and all of the reagents were edible.•The conjugates had greater radical-scavenging activity than the flavan-3-ols.•The flavan-3-ol-cysteine conjugates were active against α-glucosidase.Flavan-3-ol derivatives, including 3 cysteine conjugates and 3 acetylcysteine conjugates, were prepared using Cynomorium songaricum and edible reagents. The structures were determined, based on NMR and MS spectra. All compounds had stronger radical-scavenging activity than catechin and epicatechin. Moreover, the cysteine conjugates were active against α-glucosidase, whereas catechin and epicatechin were not. Two acetylcysteine flavan-3-ol conjugates, 4β-(l-acetylcysteinyl)-epicatechin 3-O-gallate and 4β-(l-acetylcysteinyl)-epiafzelechin, are novel compounds with better log P values than their cysteine counterparts. These conjugates can be prepared from purified flavan-3-ol polymers or directly from herbal material.

Nine compounds including a new A-type proanthocyanidin trimer, epicatechin-(2β→O→7,4β→8)-[catechin-(6→4β)]-epicatechin (8), and a known trimer, epicatechin-(4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (9), being reported for peanut skin for the first time, were isolated and purified. Their structures were determined by spectroscopic methods and by degradation reactions with l-cysteine in acidic conditions. The DPPH radical scavenging activity and the inhibitory activity on maltase and sucrase of the isolated compounds were investigated. All compounds showed strong DPPH scavenging activities (EC50 < 20 μg/mL). Compound 8 showed the strongest inhibitory activity on maltase with an IC50 value of 0.088 mg/mL, while compound 9 exhibited the strongest inhibition on sucrase with an IC50 value of 0.091 mg/mL.

Ultra-high-performance liquid chromatography–triple quadrupole mass spectrometry with dynamic selected reaction monitoring mode was developed to simultaneously quantify Ganoderma acids and alcohols. Cholic acid and hydrocortisone, whose physiochemical properties are similar to triterpene acids and alcohols, respectively, were added as internal standards before sample treatment. The method could be applied to the quantification of triterpenes in single fungus and traditional Chinese medicine preparations. This method also detected 5 triterpenes in the Coriolus genus for the first time.Graphical abstractHighlights► An UHPLC-dynamic-SRM method was developed to quantify Ganoderma acids and alcohols. ► Sample pretreatment was simple. ► The linearity of the calibration curves was satisfactory. ► The LLOQs of the triterpene acids and alcohols were 5–25 ng/mL. ► Could quantify triterpenes in single fungus and in complex TCM preparations.

The synthesized chlorogenic, quinic, and caffeic acid derivatives with antifungal activity were investigated on their metabolism and biotransformation properties in rats detected by optimized UPLC–APCI-MS/MS conditions. The metabolic scheme was deduced from the molecular fragments detected in biotransformed samples in vivo. The ion sources of APCI and ESI under positive or negative ion polarity mode for detection molecular fragments were compared to create the optimized UPLC–MS/MS conditions. The plasma and biliary samples from rats after oral or intravenous administration of the compounds were analyzed for their biotransformation in vivo. The absorption, distribution, hepatic metabolism, and disposal from systemic circulation of the substrates, and isomerization of their metabolites would be finished in 4 h after oral administration. The detection of the metabolites after HCHO, H2N-orn-4-(octyloxy) aniline, and CH4 elimination, and isomerization of their metabolites illustrated for the metabolic pathway of chlorogenic and quinic acid derivates in vivo. Caffeic acid was found to dissociate easily from chlorogenic and caffeic acid derivatives in vivo, whereas quinic acid derivative seemed more stable in the systemic circulation of rats but had the tendency to isomerize in hepatic metabolism. In addition, in vitro incubation of the 3 substrates with pooled rat liver microsomes confirmed that CYP450 played the role in catalysis for biotransformation of these compounds.Graphical abstractHighlights► Biotransformation of chlorogenic, quinic, caffeic acid derivatives was investigated. ► Metabolic scheme was deduced from the molecular fragments detected by UPLC–MS/MS. ► Isomerization of their metabolites was identified by extracted ion chromatography.

Eleven compounds were isolated from potato peels and identified. Their structures were determined by interpretation of UV, MS, 1D, and 2D NMR spectral data and by comparison with reported data. The main components of the potato peels were found to be chlorogenic acid and other phenolic compounds, accompanied by 2 glycoalkaloids, 3 low-molecular-weight amide compounds, and 2 unsaturated fatty acids, including an omega-3 fatty acid. The potato peels showed more potent radical scavenging activity than the flesh. The quantification of the 11 components indicated that the potato peels contained a higher amount of phenolic compounds than the flesh. These results suggest that peel waste from the industry of potato chips and fries may be a source of useful compounds for human health.Highlights► Phenolics, alkaloids, amides and unsaturated fatty acids were found in potato peels. ► More potent radical scavenging activity was found in potato peels than in the flesh. ► Potato peel waste may be a source of useful compounds.

New derivatives of caffeic acid and quinic acid were synthesized and their anti-fungal and inhibitory activities on fungal 1,3-β-glucan synthase were determined in comparison with those of the corresponding chlorogenic acid derivatives. All the chlorogenic, quinic and caffeic acid derivatives that were coupled with an H2N-orn-4-(octyloxy) aniline group (1, 1b and 1c) displayed potent activities in both anti-fungal and inhibition of 1,3-glucan synthase assays. Compounds 1 and 1c inhibited the fungal membrane enzyme with the potency comparable to that of a known 1,3-β-d-glucan synthase inhibitor, aculeacin A. The results revealed that the anti-fungal activity of the chlorogenic acid derivative with a free amino group was at least partly due to inhibition of the fungal 1,3-β-glucan synthase. These results suggest that further investigation on caffeic acid derivatives may lead to the discovery of novel anti-fungal agents with drug-like properties.

Ethnopharmacological relevanceThe dried fruit of Terminalia chebula (fructus chebulae) is an important Traditional Medicine used for intestinal and hepatic detoxification. Gurigumu-7 which is made of fructus chebulae and 6 other traditional medicines is one of the most frequently used compound Mongolian and Tibet medicines for liver diseases. Terminalia phenolics are considered as the bioactive constituents of fructus chebulae and consequently of Gurigumu-7.Aim of the studyTo compare the pharmacokinetic profiles of Terminalia phenolics after intragastric administration of the aqueous extracts of fructus chebulae and Gurigumu-7 and to evaluate the possible influence of intestinal bacterial metabolism on these pharmacokinetic profiles.Materials and methodsAn ultra performance liquid chromatography with triple quadrupole mass spectrometry method was established and validated for simultaneously determining the pharmacokinetic profiles of seven Terminalia phenolics after intragastric administration of pure compounds, fructus chebulae extract, and Gurigumu-7 extract. In vitro rat fecal lysates experiments were carried out to explore the metabolic discrepancy between fructus chebulae and Gurigumu-7.ResultsSeven Terminalia phenolics were detected in rat plasma after intragastric administration of the aqueous extracts of fructus chebulae and Gurigumu-7. Administration of Gurigumu-7 could promote the absorption and increase the Cmax and AUC values of these phenolic constituents compared to fructus chebulae administration. The fecal lysates studies showed that the Terminalia phenolics in Gurigumu-7 were less rapidly bio-transformed than those in fructus chebulae. This may be a contributing factor to the pharmacokinetic discrepancy between the phenolics in fructus chebulae and Gurigumu-7.ConclusionAdministration of Gurigumu-7 could increase the absorption of Terminalia phenolics through slowing down the intestinal bacteria metabolism. These results provide, in part, an in vivo rationale for the formulation of the traditional Mongolia / Tibet medicine, Gurigumu-7.Download high-res image (173KB)Download full-size image