Two new phenolic glucosides, 1-O-benzyl-6-O-E-caffeoyl-β-d-glucopyranoside and 1-O-(7S,8R)-guaiacylglycerol-(6-O-E-caffeoyl)-β-d-glucopyranoside, were isolated from the aerial parts of Lagerstroemia speciosa, along with ten known compounds. The structures of the isolated compounds were determined based on 1D- and 2D-NMR, Q-TOF MS and optical rotation spectroscopic data. All of the compounds showed moderate inhibitory activities against nitric oxide production in lipopolysaccharide-treated RAW264.7 cells, with IC50 values of 69.5-83.3 μM.

Two new natural compounds, (1R,2E)-2-(6-hydroxyhexylidene)cyclopropyl-β-D-glucopyranoside (1) and (6E)-6-[(2R)-2-(β-D-glucopyranosyloxy)cyclopropylidene]hexanoic acid (2), glucosides of a very rare methylidenecyclopropane alcohol, as well as two known glycosides of phenolic acids, namely 4-O-β-D-glucopyranosylcaffeic acid (3) and (E)-4-O-β-D-glucopyranosylcoumaric acid (4), and methyl α-fructofuranoside (5) were isolated for the first time from the rhizomes of the tree fern Metaxya rostrata C.Presl. The structures were elucidated on the basis of detailed spectroscopic data analysis, and the structure of 1 was additionally confirmed by X-ray crystal-structure analysis.

In this study, four new lignan glucosides, named difengpiosides A-D (1-4), were isolated from the stem barks of Illicium difengpi, together with seven known compounds 5-11. Their structures were identified on the basis of spectroscopic analyses (1D and 2D NMR, HRESIMS, CD) and a comparison with literature data. All the compounds were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.

Honeybees (Apis mellifera) pollinate flowers and collect nectar from many important crops. White clover (Trifolium repens) is widely grown as a temperate forage crop, and requires honeybee pollination for seed set. In this study, using a quantitative LC-MS (Liquid Chromatography-Mass Spectrometry) assay, we show that the cyanogenic glucosides linamarin and lotaustralin are present in the leaves, sepals, petals, anthers, and nectar of T. repens. Cyanogenic glucosides are generally thought to be defense compounds, releasing toxic hydrogen cyanide upon degradation. However, increasing evidence indicates that plant secondary metabolites found in nectar may protect pollinators from disease or predators. In a laboratory survival study with chronic feeding of secondary metabolites, we show that honeybees can ingest the cyanogenic glucosides linamarin and amygdalin at naturally occurring concentrations with no ill effects, even though they have enzyme activity towards degradation of cyanogenic glucosides. This suggests that honeybees can ingest and tolerate cyanogenic glucosides from flower nectar. Honeybees retain only a portion of ingested cyanogenic glucosides. Whether they detoxify the rest using rhodanese or deposit them in the hive should be the focus of further research.

Twelve galloyl glucosides 1-12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9), ethyl 2,3-di-O-galloyl-α-D-glucopyranoside (11) and ethyl 2,3-di-O-galloyl-β-D-glucopyranoside (12), are new compounds and other six, 1,6-di-O-galloyl-β-D-glucopyranose (1), 1,4,6-tri-O-galloyl-β-D-glucopyranose (2), 1,2-di-O-galloyl-β-D-glucopyranose (3), 1,3-di-O-galloyl-β-D-glucopyranose (4), 1,2,3-tri-O-galloyl-α-D-glucopyranose (6) and methyl 3,4,6-tri-O-galloyl-α-D-glucopyranoside (10), were synthesized for the first time in the present study. In in vitro MTT assay, 1-12 inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC50 values were determined to be varied in 17.2-124.7 μM on the tested three human cancer cell lines. In addition, compounds 1-12 inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in the in vitro MTT assay, and in vivo antitumor activity of 1 and 2 was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control.

2-O-α-d-Glucopyranosyl-l-ascorbic acid (AA-2G) is one of the stable ascorbic acid (AA) derivatives known as provitamin C agents. We have previously synthesized two types of monoacylated derivatives of AA-2G, 6-O-acyl-2-O-α-d-glucopyranosyl-l-ascorbic acids having a straight-acyl chain of varying length from C₄ to C18 (6-sAcyl-AA-2G) and a branched-acyl chain of varying length from C₆ to C16 (6-bAcyl-AA-2G) in order to improve the bioavailability of AA-2G. In this study, 6-sAcyl-AA-2G and 6-bAcyl-AA-2G per se showed the inhibitory effects on hyaluronidase activity and degranulation. 6-sAcyl-AA-2G exhibited strong inhibitory effects on hyaluronidase activity and degranulation in a concentration-dependent manner, and the inhibitory effects tended to become stronger with increasing length of the acyl chain. 2-O-α-d-Glucopyranosyl-6-O-hexadecanoyl-l-ascorbic acid (6-sPalm-AA-2G), which has a straight C16 acyl chain, was the most potent effective for inhibition of hyaluronidase activity and for inhibition of degranulation among the 6-sAcyl-AA-2G derivatives and the two isomers of 6-sPalm-AA-2G. Furthermore, percutaneous administration of 6-sPalm-AA-2G significantly inhibited IgE-mediated passive cutaneous anaphylaxis reaction in mice. These findings suggest that 6-sPalm-AA-2G will be useful for treatment of allergies.

Flavonols are efficient antioxidants with the potential to protect biological macromolecules from oxidative damage in vivo, and if absorbed into the circulation they may protect against cardiovascular disease. Although flavonol aglycones are present in foods at low concentrations, their glycosides are abundant in onions, apples, beans and tea, and are thought to be stable under the conditions of the human stomach and small bowel. There is, however, recent evidence to suggest that intact glycosides of quercetin may be absorbed from the small intestine by a mechanism involving the glucose transport pathway. In the present study we tested this hypothesis by measuring the effect of quercetin glycosides on the rate of efflux of galactose from the jejunal mucosa. Everted sacs of rat jejunum preloaded with 14C-galactose were exposed to quercetin glycosides isolated from onions. Quercetin mono- and diglucosides were shown to accelerate the carrier-mediated efflux of galactose via a sodium-dependent pathway. HPLC analysis confirmed the stability of the glycosides under conditions simulating those in the upper alimentary tract. These studies suggest that purified quercetin glucosides are capable of interacting with the sodium dependent glucose transport receptors in the mucosal epithelium and may therefore be absorbed by the small intestine in vivo.

An activity-guided fractionation approach revealed several phenylpropanoid glycerol glucosides isolated from the bulbs of Lilium longiflorum Thunb. (Easter lily) with gluconeogenesis inhibitory activities. The strongest activity was observed for (2S)-1-O-p-coumaroyl-2-O-β-d-glucopyranosylglycerol (3), (2S)-1-O-caffeoyl-2-O-β-d-glucopyranosylglycerol (1), and (2R)-1-O-β-d-glucopyranosyl-2-O-p-coumaroylglycerol (2) with inhibitions of 51.2, 39.2, and 36.8%, respectively. The p-coumaroyl-based (3) and its acetylated derivative (5) exhibited differential inhibition activity (51.2% as compared to 3.6%), suggesting that natural acetylation decreases the hypoglycemic activity of these compounds. Direct structure-activity analysis of phenylpropanoid glycerol glucosides indicated that the hydroxylation pattern of the hydroxy cinnamic acid moiety and acetylation were responsible for the differences in activity. This is the first report of phenylpropanoid glycerol glucosides as a phytochemical class of hepatic glucose production inhibitors.

Cytokinins (CKs) are a class of phytohormones affecting many aspects of plant growth and development. In the complex process of CK homeostasis in plants, N-glucosylation represents one of the essential metabolic pathways. Its products, CK N7- and N9-glucosides, have been largely overlooked in the past as irreversible and inactive CK products lacking any relevant physiological impact. In this work, we report a widespread distribution of CK N-glucosides across the plant kingdom proceeding from evolutionary older to younger plants with different proportions between N7- and N9-glucosides in the total CK pool. We show dramatic changes in their profiles as well as in expression levels of the UGT76C1 and UGT76C2 genes during Arabidopsis ontogenesis. We also demonstrate specific physiological effects of CK N-glucosides in CK bioassays including their antisenescent activities, inhibitory effects on root development, and activation of the CK signaling pathway visualized by the CK-responsive YFP reporter line, TCSv2::3XVENUS. Last but not least, we present the considerable impact of CK N7- and N9-glucosides on the expression of CK-related genes in maize and their stimulatory effects on CK oxidase/dehydrogenase activity in oats. Our findings revise the apparent irreversibility and inactivity of CK N7- and N9-glucosides and indicate their involvement in CK evolution while suggesting their unique function(s) in plants.

Cytokinin is an indispensable phytohormone responsible for physiological processes ranging from root development to leaf senescence. The term "cytokinin" refers to several dozen adenine-derived compounds occurring naturally in plants. Cytokinins (CKs) can be divided into various classes and forms; base forms are generally considered to be active while highly abundant cytokinin-N-glucosides (CKNGs), composed of a CK base irreversibly conjugated to a glucose molecule, are considered inactive. However, results from early CK studies suggest CKNGs do not always lack activity despite the perpetuation over several decades in the literature that they are inactive. Here we show that exogenous application of trans-Zeatin-N-glucosides (tZNGs, a specific class of CKNGs) to Arabidopsis results in CK response comparable to the application of an active CK base. These results are most apparent in senescence assays where both a CK base (tZ) and tZNGs (tZ7G, tZ9G) delay senescence in cotyledons. Further experiments involving root growth and shoot regeneration revealed tZNGs do not always have the same effects as tZ, and have largely distinct effects on the transcriptome and proteome. These data are in contrast to previous reports of CKNGs being inactive and raise questions about the function of these compounds as well as their mechanism of action.

A new 8,4'-oxyneolignane glucoside 1 has been isolated from the stems of Dendrobium aurantiacum var. denneanum together with six known phenolic glucosides 2−7. The structure of the new compound, including its absolute configuration, was determined by spectroscopic and chemical methods as (−)-(7S,8R,7'E)-4-hydroxy-3,3',5,5'-tetramethoxy-8,4'-oxyneolign-7'-ene-7,9,9'-triol 7,9'-bis-O-β-D-glucopyranoside (1). In the in vitro assays, compound 1 and (−)-syringaresinol-4,4'-bis-O-β-D-glucopyranoside (2) showed evident activity against glutamate-induced neurotoxicity in PC12 cells. Shashenoside I (4) showed a selective cytotoxic activity with the IC₅₀ value of 4.17 μM against the acute myeloid leukemia cell line MV4-11, while it was inactive against 10 other human tumor cell lines.

Therapeutically active glycosylated phytochemicals are ubiquitous in the human diet. The human gut microbiota (HGM) modulates the bioactivities of these compounds, which consequently affect host physiology and microbiota composition. Despite a significant impact on human health, the key players and the underpinning mechanisms of this interplay remain uncharacterized. Here, we demonstrate the growth of Lactobacillus acidophilus on mono- and diglucosyl dietary plant glycosides (PGs) possessing small aromatic aglycones. Transcriptional analysis revealed the upregulation of host interaction genes and identified two loci that encode phosphotransferase system (PTS) transporters and phospho-β-glucosidases, which mediate the uptake and deglucosylation of these compounds, respectively. Inactivating these transport and hydrolysis genes abolished or severely reduced growth on PG, establishing the specificity of the loci to distinct groups of PGs. Following intracellular deglucosylation, the aglycones of PGs are externalized, rendering them available for absorption by the host or for further modification by other microbiota taxa. The PG utilization loci are conserved in L. acidophilus and closely related lactobacilli, in correlation with versatile growth on these compounds. Growth on the tested PG appeared more common among human gut lactobacilli than among counterparts from other ecologic niches. The PGs that supported the growth of L. acidophilus were utilized poorly or not at all by other common HGM strains, underscoring the metabolic specialization of L. acidophilus These findings highlight the role of human gut L. acidophilus and select lactobacilli in the bioconversion of glycoconjugated phytochemicals, which is likely to have an important impact on the HGM and human host.IMPORTANCE Thousands of therapeutically active plant-derived compounds are widely present in berries, fruits, nuts, and beverages like tea and wine. The bioactivity and bioavailability of these compounds, which are typically glycosylated, are altered by microbial bioconversions in the human gut. Remarkably, little is known about the bioconversion of PGs by the gut microbial community, despite the significance of this metabolic facet to human health. Our work provides the first molecular insights into the metabolic routes of diet relevant and therapeutically active PGs by Lactobacillus acidophilus and related human gut lactobacilli. This taxonomic group is adept at metabolizing the glucoside moieties of select PG and externalizes their aglycones. The study highlights an important role of lactobacilli in the bioconversion of dietary PG and presents a framework from which to derive molecular insights into their metabolism by members of the human gut microbiota.

On-farm extraction of commercially important essential oil from aromatic crops generates huge spent aromatic waste. This massive waste is often disposed in the unregulated landfills or burned in the open air to vacate the fields. Hence, a new method for processing of aromatic spent waste has been developed to obtain platform chemicals, such as, xylose and ethyl glucosides. The thermochemical liquefaction of acid pre-treated palmarosa (cymbopogon martini) biomass furnished a mixture of ethyl glucopyranosides in good yield (∼17 wt% relative to biomass) and selectivity (∼77%) by heating with p-cymen-2-sulphonic acid (p-CSA) in the presence of ethanol as a solvent. The detection, quantification and isolation of ethyl glucosides may provide a new application of spent aromatic biomass for use as a feed stock in the production of value added chemicals.

Glucoside natural products have been showing great medicinal values and potentials. However, the production of glucosides by plant extraction, chemical synthesis, and traditional biotransformation is insufficient to meet the fast-growing pharmaceutical demands. Microbial synthetic biology offers promising strategies for synthesis and diversification of plant glycosides.

Three new compounds: 2R,3R-pterosin L 3-O-beta-D-glucopyranoside (1), beta-D-xylopyranosyl(1-->2)-7-O-benzoyl-beta-D-glucopyranoside (2) and 4-O-benzoyl-beta-D-xylo-pyranosyl(1-->2)-7-O-benzoyl-beta-D-glucopyranoside (3), together with nine known compounds, were isolated from the ethyl acetate extract of Pteris ensiformis. 5-[2-Hydroxyethylidene]-2(5H)-furanone (4), which had been synthesized, was isolated from natural sources for the first time. The structures of all isolated compounds were determined on the basis of mass and spectroscopic evidence. Compound 1 and pterosin B (5) show cytotoxicity against HL 60 cells (human leukemia) with the IC(50) values of 3.7 and 8.7 microg/mL, respectively.

Carthamus tinctorius L. (Compositae; safflower or Hong Hua) has been used in Korean traditional medicine for maintaining the homeostasis of body circulation. Phytochemical investigation was performed on the florets of C. tinctorius by liquid chromatography-mass spectrometry (LC/MS), which afforded two dihydrophaseic acid glucosides (1 and 2). Isolated compounds were structurally confirmed using a combination of spectroscopic methods including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectroscopy. Their absolute configurations were established by quantum chemical electronic circular dichroism calculations and enzymatic hydrolysis. The anti-adipogenesis activity of the isolated compounds was evaluated using 3T3-L1 preadipocytes. Treatment with the dihydrophaseic acid glucoside (1) during adipocyte differentiation prevented the accumulation of lipid droplets and reduced the expression of adipogenic genes, Fabp4 and Adipsin. However, compound 2 did not affect adipogenesis. Our study yielded a dihydrophaseic acid glucoside derived from C. tinctorius, which has potential advantages for treating obesity.

Anthraquinones, naturally occurring bioactive compounds, have been reported to exhibit various biological activities, including anti-inflammatory, antiviral, antimicrobial, and anticancer effects. In this study, we biotransformed three selected anthraquinones into their novel O-glucoside derivatives, expressing a versatile glycosyltransferase (YjiC) from Bacillus licheniformis DSM 13 in Escherichia coli. Anthraflavic acid, alizarin, and 2-amino-3-hydroxyanthraquinone were exogenously fed to recombinant E. coli as substrate for biotransformation. The products anthraflavic acid-O-glucoside, alizarin 2-O-β-d-glucoside, and 2-amino-3-O-glucosyl anthraquinone produced in the culture broths were characterized by various chromatographic and spectroscopic analyses. The comparative anti-proliferative assay against various cancer cells (gastric cancer-AGS, uterine cervical cancer-HeLa, and liver cancer-HepG2) were remarkable, since the synthesized glucoside compounds showed more than 60% of cell growth inhibition at concentrations ranging from ~50 μM to 100 μM. Importantly, one of the synthesized glucoside derivatives, alizarin 2-O-glucoside inhibited more than 90% of cell growth in all the cancer cell lines tested.

Two new triterpenoid glucosides, Heritiera A (1) and Heritiera B (2), and six known triterpenoid analogs (3-8) were isolated from Heritiera littoralis Dryand. Their structures were identified by comprehensive spectroscopic analyses and comparisons with the literature. The anti-inflammatory activity of the isolates from H. littoralis was evaluated using a lipopolysaccharide (LPS) stimulated RAW 264.7 cells model. The result showed that four triterpenoids exhibited potent anti-inflammatory activity. Among these compounds, compound 2 substantially inhibits the release of nitric oxide (NO) with an IC50 value of 10.33 μM. The triterpenoids from H. littoralis could be used as potential candidates for the development of new anti-inflammatory agents.

Two-component plant defenses such as cyanogenic glucosides are produced by many plant species, but phloem-feeding herbivores have long been thought not to activate these defenses due to their mode of feeding, which causes only minimal tissue damage. Here, however, we report that cyanogenic glycoside defenses from cassava (Manihot esculenta), a major staple crop in Africa, are activated during feeding by a pest insect, the whitefly Bemisia tabaci, and the resulting hydrogen cyanide is detoxified by conversion to beta-cyanoalanine. Additionally, B. tabaci was found to utilize two metabolic mechanisms to detoxify cyanogenic glucosides by conversion to non-activatable derivatives. First, the cyanogenic glycoside linamarin was glucosylated 1-4 times in succession in a reaction catalyzed by two B. tabaci glycoside hydrolase family 13 enzymes in vitro utilizing sucrose as a co-substrate. Second, both linamarin and the glucosylated linamarin derivatives were phosphorylated. Both phosphorylation and glucosidation of linamarin render this plant pro-toxin inert to the activating plant enzyme linamarase, and thus these metabolic transformations can be considered pre-emptive detoxification strategies to avoid cyanogenesis.

Puerarin (PU) is the most abundant isoflavone from the root of Pueraria lobata and exhibits a broad range of pharmacological activities. However, poor water solubility and low bioavailability limit its use. Enzymatic transglycosylation is emerging as a new strategy to improve the pharmacodynamic and pharmacokinetic properties of natural products for drug development. In this study, three PU glucosides (PU-G, PU-2G, and PU-3G) were synthesized by using a cyclodextrin glucanotransferase from Bacillus licheniformis with PU as the acceptor and α-cyclodextrin as the sugar donor. The transglycosylation products were isolated and structurally identified by mass spectrometry and nuclear magnetic resonance. The water solubilities of PU-G, PU-2G, and PU-3G were 15.6, 100.9, and 179.1 times higher than that of PU, respectively. Moreover, the antiosteoporosis activities of these glucosides were tested, and PU-G was found to show much more potent antiosteoporosis activity as compared to the original PU.