Phenolic Glycosides from Viburnum chinshanense Leaves and their α-Amylase and α-Glucosidase Inhibitory Activity.

The phytochemical investigation of Viburnum chinshanense leaves led to the isolation and identification of four new phenolic glycosides, viburninsides A-D (1-4), and eight known analogues (5-12). The structures of the four undescribed compounds were determined by spectroscopic techniques, including 1D NMR, 2D NMR, and HRESIMS, and their containing sugar units were confirmed by acid hydrolysis and HPLC analysis of the monosaccharide's chiral derivatives. Additionally, the α-amylase and α-glucosidase inhibitory activities of the isolated compounds were assessed. Compounds 1, 2, 4, 9, and 10 exhibited potential inhibitory activities against α-amylase and α-glucosidase with IC50 values ranging from 35.07 µM to 47.42 µM and 18.27 µM to 43.65 µM, respectively. Molecular docking analysis of compound 4 with the strongest inhibition against the target enzymes was also conducted.

Five New Phenolic Glycosides from Viburnum luzonicum.

Viburnum luzonicum is widely distributed in China. Its branch extracts showed potential α-amylase and α-glucosidase inhibitory activities. In order to discover new bioactive constituents, five undescribed phenolic glycosides, viburozosides A-E (1-5), were obtained by bioassay-guided isolation coupled with HPLC-QTOF-MS/MS analysis. Their structures were elucidated by spectroscopic analyses, including 1D NMR, 2D NMR, ECD, and ORD. All compounds were tested for their α-amylase and α-glucosidase inhibitory potency. Compound 1 showed significantly competitive inhibition against α-amylase (IC50 =17.5 µM) and α-glucosidase (IC50 =13.6 µM).

Undescribed Phenolic Glycosides from Syzygium attopeuense and Their Inhibition of Nitric Oxide Production.

Four undescribed phenolic glycosides including three stilbene derivatives (1 and 3) and sodium salt of 3 (2), and a chalcone glycoside (4), together with thirteen known compounds (5-17) were isolated from the leaves of Syzygium attopeuense (Gagnep.) Merr. & L.M.Perry. Their chemical structures were elucidated to be (Z)-gaylussacin (1), 6''-O-galloylgaylussacin sodium salt (2), 6''-O-galloylgaylussacin (3), 4'-O-[ß-D-glucopyranosyl-(1→6)-glucopyranosyl]oxy-2'-hydroxy-6'-methoxydihydrochalcone (4), gaylussacin (5), pinosilvin 3-O-ß-D-glucopyranoside (6), myricetin-3-O-(2''-O-galloyl)-α-L-rhamnopyranoside (7), myricetin-3-O-(3''-O-galloyl)-α-L-rhamnopyranoside (8), myricetin-3-O-α-L-rhamnopyranoside (9), quercitrin (10), myricetin-3-O-ß-D-glucopyranoside (11), myricetin-3-O-ß-D-galactopyranoside (12), quercetin 3-O-α-L-arabinopyranoside (13), myricetin-3-O-2''-O-galloyl)-α-L-arabinopyranoside (14), (+)-gallocatechin (15), (-)-epigallocatechin (16), and 3,3',4'-trimethoxyellagic acid 4-O-ß-D-glucopyranoside (17) by the analysis of HR-ESI-MS, 1D and 2D NMR spectra in comparison with the previously reported data. Compounds 1-3, 5, and 6 significant inhibition of NO production in LPS-activated RAW264.7 cells, with IC50 values ranging from 18.37±1.38 to 35.12±2.53 µM, compared to a positive control (dexamethasone) with an IC50 value of 15.37±1.42 µM.

Phenolic Glycosides from the Leaves of Iodes cirrhosa Turcz. with Cytotoxic and Antimicrobial Effects.

In the present study, 14 phenolic glycosides, including one new neolignan glycoside, iodescirrhoside A (1), three new flavonol glycosides, iodescirrhosides B-D (2-4), and 10 known metabolites were obtained from the methanol extract of Iodes cirrhosa leaves. Structural elucidation was performed by interpretating the 1D- and 2D- NMR, HR-ESI-MS, and CD spectra in comparison with literature data. All compounds were noncytotoxic to LU-1, HepG2, MCF-7, SK-Mel-2, and LNCaP cancer cell lines. Compound 11 significantly inhibited the growth of E. faecalis. In contrast, weak inhibition was observed for 1-9 and 14 against E. faecalis, for 1, 6-8, and 11 against S. aureus, for 6 and 13 against B. cereus, and 2, 4, and 6-9 against C. albicans.

Two new phenolic glycosides from the fruits of Illicium verum.

Two new phenolic glycosides (1-2) and eleven known compounds (3-13) were isolated from the fruits of Illicium verum Hook.f. using silica-gel column and preparative middle pressure liquid chromatography (MPLC). The structures of the compounds were elucidated by NMR spectroscopic data. Among them, compounds 3, 5, and 10 were isolated from the family Magnoliaceae for the first time. Additionally, all the compounds were evaluated for their anti-complementary activities against the classical pathway (CP) and the alternative pathway (AP).

Anti-inflammatory active components of the roots of Datura metel.

One new phenolic glycoside, methyl 3,4-dihydroxyphenylacetate-4-O-[2-O-ß-D-apisoyl-6-O-(2-hydroxybenzoyl)]-ß-D-glucopyranoside (1), together with 10 known compounds (2-11), were isolated from the roots of Datura metel. The structures of these compounds were elucidated on the basis of their spectroscopic data. Furthermore, the in vitro anti-inflammatory activities of compounds 1-11 were evaluated.[Formula: see text].

Discovery of Phenolic Glycoside from Hyssopus cuspidatus Attenuates LPS-Induced Inflammatory Responses by Inhibition of iNOS and COX-2 Expression through Suppression of NF-κB Activation.

It seems quite necessary to obtain effective substances from natural products against inflammatory response (IR) as there are presently clinical problems regarding accompanying side effects and lowered quality of life. This work aimed to investigate the abilities of hyssopuside (HY), a novel phenolic glycoside isolated from Hyssopus cuspidatus (H. cuspidatus), against IR in lipopolysaccharide (LPS)-induced RAW 264.7 cells and mouse peritoneal macrophages. The results indicated that HY could reduce nitric oxide (NO) production and inhibit the production and secretion of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in LPS-stimulated macrophages. Moreover, data from the immunofluorescence study showed that HY suppressed nuclear translocation of nuclear factor-kappa B (NF-κB) upon LPS induction. The Western blot results suggested that HY reversed the LPS-induced degradation of IκB (inhibitor of NF-κB), which is normally required for the activation of NF-κB. Meanwhile, the overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) diminished significantly with the presence of HY in response to LPS stimulation. On the other hand, HY had a negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. Moreover, an in silico study of HY against four essential proteins/enzymes revealed that COX-2 was the most efficient enzyme for the interaction, and binding of residues Phe179, Asn351, and Ser424 with HY played crucial roles in the observed activity. The structure analysis indicated the typical characterizations with phenylethanoid glycoside contributed to the anti-inflammatory effects of HY. These results indicated that HY manipulated its anti-inflammatory effects mainly through blocking the NF-κB signal transduction pathways. Collectively, we believe that HY could be a potential alternative phenolic agent for alleviating excessive inflammation in many inflammation-associated diseases.

Metabolic engineering of Saccharomyces cerevisiae for high-level production of gastrodin from glucose.

BACKGROUND: The natural phenolic glycoside gastrodin is the major bioactive ingredient in the well-known Chinese herb Tianma and is widely used as a neuroprotective medicine in the clinic. Microbial production from sustainable resources is a promising method to replace plant extraction and chemical synthesis which were currently used in industrial gastrodin production. Saccharomyces cerevisiae is considered as an attractive host to produce natural plant products used in the food and pharmaceutical fields. In this work, we intended to explore the potential of S. cerevisiae as the host for high-level production of gastrodin from glucose. RESULTS: Here, we first identified the plant-derived glucosyltransferase AsUGT to convert 4-hydroxybenzyl alcohol to gastrodin with high catalytic efficiency in yeast. Then, we engineered de novo production of gastrodin by overexpressing codon-optimized AsUGTsyn, the carboxylic acid reductase gene CARsyn from Nocardia species, the phosphopantetheinyl transferase gene PPTcg-1syn from Corynebacterium glutamicum, the chorismate pyruvate-lyase gene UbiCsyn from Escherichia coli, and the mutant ARO4K229L. Finally, we achieved an improved product titer by a chromosomal multiple-copy integration strategy and enhancement of metabolic flux toward the aglycon 4-hydroxybenzyl alcohol. The best optimized strain produced 2.1 g/L gastrodin in mineral medium with glucose as the sole carbon source by flask fermentation, which was 175 times higher than that of the original gastrodin-producing strain. CONCLUSIONS: The de novo high-level production of gastrodin was first achieved. Instead of chemical synthesis or plants extraction, our work provides an alternative strategy for the industrial production of gastrodin by microbial fermentation from a sustainable resource.

Matteuinterins A-C, three new glycosides from the rhizomes of Matteuccia intermedia.

Phytochemical investigation on the rhizomes of Matteuccia intermedia C.Chr. led to the isolation of three new compounds, named matteuinterins A-C (1-3), together with seven known compounds (4-10). Their structures were elucidated by extensive NMR analyses and chemical derivatization. Compounds 5-10 were evaluated for their anti-inflammatory activities on PGE2 release in LPS-stimulated RAW 264.7 murine macrophages. Compounds 5 and 10 exhibited inhibitory effect on PGE2 production in LPS-activated murine macrophages with IC50 values of 17.8 ± 1.5 and 30.3 ± 2.1 µM, respectively.[Formula: see text].

[A new phenolic glycoside from honey-fried Eriobotrya japonica].

A total of twelve compounds were isolated from the ethyl acetate of the water extract of honey-fried Eriobotrya japonica through column chromatography over silica gel,Sephadex LH-20,RP-18,and preparative HPLC. Their structures were established by MS,1 D NMR and 2 D NMR data as japonicanoside A( 1),nerolidol-3-O-α-L-rhamnopyranosyl-( 1→2)-ß-D-glucopyranoside( 2),nerolidol-3-O-α-L-rhamnopyranosyl-( l→4)-α-L-rhamnopyranosyl-( 1 → 2)-[α-L-( 4-trans-feruloyl)-rhamnopyranosyl-( 1 → 6) ]-ß-D-glucopyranoside( 3),( +)-catechin( 4),(-)-epicatechin( 5),kaempferol 3-O-α-L-rhamnopyranoside( 6),quercitrin( 7),quercetin-3-O-ß-D-galactopyranoside( 8),quercetin-3-O-ß-glucopyranoside( 9),vanillin( 10),protocatechuic aldehyde( 11),and maltol( 12). Among them,1 is a new phenolic glycoside.

The effects of phenolic glycosides from Betula platyphylla var. japonica on adipocyte differentiation and mature adipocyte metabolism.

Betula platyphylla var. japonica (Betulaceae) has been used traditionally in Asian countries for the treatment of inflammatory diseases. A recent study has reported a phenolic compound, platyphylloside from B. platyphylla, that shows inhibition on adipocyte differentiation and induces lipolysis in 3T3-L1 cells. Based on this finding, we conducted phytochemical analysis of the EtOH extract of the bark of B. platyphylla var. japonica, which resulted in the isolation of phenolic glycosides (1-4). Treatment of the isolated compounds (1-4) during adipocyte differentiation of 3T3-L1 mouse adipocytes resulted in dose-dependent inhibition of adipogenesis. In mature adipocytes, arylbutanoid glycosides (2-4) induced lipolysis related genes HSL and ATGL, whereas catechin glycoside (1) had no effect. Additionally, arylbutanoid glycosides (2-4) also induced GLUT4 and adiponectin mRNA expression, indicating improvement in insulin signaling. This suggests that the isolates from B. platyphylla var. japonica exert benefial effects in regulation of adipocyte differentiation as well as adipocyte metabolism.

Two New Phenolic Glycosides from Sorbus commixta.

From the stem bark of Sorbus commixta, two new phenolic glycosides, sorcomisides A and B (1 and 2), were isolated along with 10 known compounds. The structures of the isolates were determined by analysis of one-dimensional and two-dimensional NMR (1D- and 2D-NMR) data and high resolution (HR)-MS, chemical reaction, and computational methods. All the isolated compounds (1-12) were tested for their neuroprotective, anti-inflammatory, and cytotoxic activities.

Preliminary Quality Evaluation and Characterization of Phenolic Constituents in Cynanchi Wilfordii Radix.

A new phenolic compound, 2-O-ß-laminaribiosyl-4-hydroxyacetophenone (1), was isolated from Cynanchi Wilfordii Radix (CWR, the root of Cynanchum wilfordii Hemsley), along with 10 known aromatic compounds, including cynandione A (2), bungeisides-C (7) and -D (8), p-hydroxyacetophenone (9), 2',5'-dihydroxyacetophenone (10), and 2',4'-dihydroxyacetophenone (11). The structure of the new compound (1) was elucidated using spectroscopic methods and chemical methods. The structure of cynandione A (2), including a linkage mode of the biphenyl parts that remained uncertain, was unambiguously confirmed using the 2D 13C-13C incredible natural abundance double quantum transfer experiment (INADEQUATE) spectrum. Additionally, health issues related to the use of Cynanchi Auriculati Radix (CAR, the root of Cynanchum auriculatum Royle ex Wight) instead of CWR have emerged. Therefore, constituents present in methanolic extracts of commercially available CWRs and CARs were examined using UV-sensitive high-performance liquid chromatography (HPLC), resulting in common detection of three major peaks ascribed to cynandione A (2), p-hydroxyacetophenone (9), and 2',4'-dihydroxyacetophenone (11). Thus, to distinguish between these ingredients, a thin-layer chromatography (TLC) method, combined with only UV irradiation detection, focusing on wilfosides C1N (12) and K1N (13) as marker compounds characteristic of CAR, was performed. Furthermore, we propose this method as a simple and convenient strategy for the preliminary distinction of CWR and CAR to ensure the quality and safety of their crude drugs.

[Chemical constituents from a Tibetan herbal medicine Corydalis hendersonii].

Nine alkaloids and two phenolic glycosides were isolated from EtOH extract of the whole plants of Corydalis hendersonii by various chromatographic techniques including silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were identified as groenlandicine (1), berberine (2), protopine (3), cryptopine (4), N-trans-feruloyloctopamine(5), 3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxyphenyl)-2-methoxyethyl] acrylamide (6), N-cis-p-coumaroyloctopamine (7), N-trans-p-coumaroylnoradrenline (8),N-cis-feruloyloctopamine (9), apocynin (10), and glucoacetosyringone (11) by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 10 and 11 were isolated from this genus for the first time, and 1, 2, and 5-9 were isolated from the species for the first time. All isolates were tested for their protection for in vitro PC12 cell line and antiplatelet aggregation activity. The results showed that compounds 5 and 7 displayed protective effects at a concentration of 10 µmol·L⁻¹, and compound 2 showed antiplatelet aggregation activity induced by THR, ADP, and AA, and compound 3 exhibted inhibitory effect induced by THR.

Chemical constituents from the stems of Hydrangea paniculata.

Further study on the constituents from the stems of Hydrangea paniculata Sieb resulted in isolation of two new compounds 1-2, including 1 monoterpenoid and 1 phenolic glycoside, along with 10 known compounds. Their structures were elucidated on the basis of spectroscopic data, including UV, IR, MS, and NMR experiments, along with chemical methods. At 10 µM, compounds 1 and 2 exhibited comparable activities with bicyclol in vitro assays for hepatoprotective activity against APAP-induced HepG2 cell damage.

Heterozygosity, gender, and the growth-defense trade-off in quaking aspen.

Although plant growth is generally recognized to be influenced by allocation to defense, genetic background (e.g., inbreeding), and gender, rarely have those factors been addressed collectively. In quaking aspen (Populus tremuloides Michx.), phenolic glycosides (PGs) and condensed tannins (CTs) constitute up to 30 % of leaf dry weight. To quantify the allocation cost of this chemical defense, we measured growth, defense chemistry, and individual heterozygosity (H obs at 16 microsatellite loci) for male and female trees in both controlled and natural environments. The controlled environment consisted of 12 juvenile genets grown for 3 years in a common garden, with replication. The natural environment consisted of 51 mature genets in wild populations, from which we sampled multiple ramets (trees) per genet. Concentrations of PGs and CTs were negatively correlated. PGs were uncorrelated with growth, but CT production represented a major cost. Across the range of CT levels found in wild-grown trees, growth rates varied by 2.6-fold, such that a 10 % increase in CT concentration occurred with a 38.5 % decrease in growth. H obs had a marked effect on aspen growth: for wild trees, a 10 % increase in H obs corresponded to a 12.5 % increase in growth. In wild trees, this CT effect was significant only in females, in which reproduction seems to exacerbate the cost of defense, while the H obs effect was significant only in males. Despite the lower growth rate of low-H obs trees, their higher CT levels may improve survival, which could account for the deficit of heterozygotes repeatedly found in natural aspen populations.

Bioactive glycosides from the roots of Ilex asprella.

Context The roots of Ilex asprella (Hook. et Arn.) Champ. ex Benth. (Aquifoliaceae) are widely used in Chinese medicine to treat influenza, amygdalitis, pertussis, etc. Their mechanism of action is still unknown, which raises the need to identify new bioactive compounds in this plant. Objective In this study, we isolated a novel saponin containing sulphonic groups, namely, asprellcoside A (1) and a known phenolic glycoside compound (2) from the roots of Ilex asprella and evaluated their bioactivities. Materials and methods Molecular structures were elucidated by analysing their spectral and chemical properties. The viability of A549 cells was tested using a MTT assay. Ability of the compounds to inhibit viruses was determined using the neuraminidase activity assay. Their anti-inflammatory effects were tested using the IP-10 activity assay using various concentrations (compound 1: 0.6, 0.2, 0.6, 1.70, 5.00 and 15.00 µM; compound 2: 0.4, 1.2, 3.6, 11.0, 33.0 and 100 µM). Their inhibitory effect on platelet aggregation induced by adenosine diphosphate (ADP) in rabbit plasma was determined at 60 and 80 µM. Results Both compounds inhibit influenza virus strain A/PuertoRico/8/1934 (H1N1) strongly with EC50 values of 4.1 and 1.7 µM, respectively. Both compounds inhibit the secretion of IP-10 with EC50 values of 6.6 and 2.5 µM, respectively. Compound 1 alone inhibited platelet aggregation significantly, with the rate of suppression being 47 ± 8 and 38 ± 3%, at 60 and 80 µM, respectively. Conclusions The results suggest that both compounds may be valid therapeutics against influenza virus infection and that compound 1 may be a novel agent for treating thrombosis.

[Studies on chemical constituents of rhizomes of Smilax trinervula].

The chemical constituents were separated and purified from the 70% ethanol extract of Smilax trinervulaby various chromatographic methods including silica gel, Sephadex LH-20, MCI and preparative HPLC. Their structures were obtained and identified by analysis of the spectroscopic data. Compounds 1-11 were separated from this genus for the first time. Compound 12 was obtained from S. trinervula for the first time.

Pheonolic Compounds from the Fruits of Viburnum sargentii Koehne.

Seven phenolic compounds were isolated from the fruits of Viburnum sargentii Koehne by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as (-)-Epicatechin (1), 5,7,4'-trihydroxy-flavonoid-8-C-ß-D-glucopyranoside (2), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propane-diol (erythro) (3), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-α-L-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (threo) (4), (R)-4-hydroxylphenol O-(6-O-oleuropeoyl)-ß-D-glucopyranoside (5), (R)-3-methoxy-4-hydroxylphenol O-(6-O-oleuropeoyl)-ß-D-glucopyranoside (6), quercetin-3-O-rutinoside (7). Compounds 5 and 6 are new monoterpene phenolic glycosides, compounds 1, 3 and 4 were isolated from the Viburnum genus for the first time, and compounds 2 and 7 from the Viburnum sargentii Koehne for the first time. Compounds 1-7 were also assayed for their antioxidant activities with DPPH free radicals.

An optimal defense strategy for phenolic glycoside production in Populus trichocarpa--isotope labeling demonstrates secondary metabolite production in growing leaves.

Large amounts of carbon are required for plant growth, but young, growing tissues often also have high concentrations of defensive secondary metabolites. Plants' capacity to allocate resources to growth and defense is addressed by the growth-differentiation balance hypothesis and the optimal defense hypothesis, which make contrasting predictions. Isotope labeling can demonstrate whether defense compounds are synthesized from stored or newly fixed carbon, allowing a detailed examination of these hypotheses. Populus trichocarpa saplings were pulse-labeled with 13CO2 at the beginning and end of a growing season, and the 13C signatures of phenolic glycosides (salicinoids), sugars, bulk tissue, and respired CO2 were traced over time. Half of the saplings were also subjected to mechanical damage. Populus trichocarpa followed an optimal defense strategy, investing 13C in salicinoids in expanding leaves directly after labeling. Salicinoids turned over quickly, and their production continued throughout the season. Salicin was induced by early-season damage, further demonstrating optimal defense. Salicinoids appear to be of great value to P. trichocarpa, as they command new C both early and late in the growing season, but their fitness benefits require further study. Export of salicinoids between tissues and biochemical pathways enabling induction also needs research. Nonetheless, the investigation of defense production afforded by isotope labeling lends new insights into plants' ability to grow and defend simultaneously.