Flavonoid C-glycosides Research Articles

Phenolic acids and C-glycoside flavonoids in Merostachys riedeliana (bamboo)

M. riedeliana is a bamboo native to Brazil that might be overabundant after the canopy disturbance of the Atlantic Forest. Previous studies showed the allelopathic and antioxidant potential of aqueous extract (AE) from leaves. The leaves were collected from specimens in the Parque Estadual das Fontes do Ipiranga, São Paulo, Brazil. A voucher specimen (SP 415223) was deposited in the Herbarium Maria Eneida Kauffman Fidalgo, IBt, SP, Brazil). The aim was to study the chemical composition of the M. riedeliana. The AE was prepared with 30 g of leaves and 600mL H2O at 60 °C for three hours. The yield of the extraction was 0.50%. The yields of the fractions obtained by liquid-liquid partition of the AE: hexane (0.028%); ethyl acetate (0.261%) and n-butanol (0.35%). The main compounds identified by LC-ESI+-MS-MS/DAD (LC-10AD, Shimadzu, Esquire 3000, Brüker) analysis of AE were the lactonic dimer of p-hydroxybenzoic (1) at Rt = 2.7 min. (225nm and 279nm) and MS/MS2 [M+H]+m/z = 254 Da and m/z = 139 (100%), the orientin, isovitexin as well as their O-glycoside derivatives. The following were found in the ethyl acetate fraction: 3, 4-methylenedioxymandelic acid (2) at Rt = 8.1 min. (225nm and 320nm), MS/MS2 [M+H]+= 393 Da and m/z = 197 (100%), the orientin ([M+H]+ m/z = 449 Da and isovitexin [M+H]+ m/z = 433 Da. The phenolic acids (BSTFA/TMS) identified by CG-MS (Agilent GC 6890, MSD 5973N, NIST) were: benzoic; benzeneacetic; salicylic; p-hydroxybenzoic; p-hydroxyphenylacetic; isovanilic; m-anisic; p-coumaric; protocatechuic; syringic; gallic; ferulic; m-coumaric; vanillylmandelic; 4-methylmandelic and (2). The AE M. riedeliana is rich in phenolic compounds and many of them have individually demonstrated antioxidant or allelopathic activity. Therefore, the synergistic effect of these combined compounds might be more effective in explaining these results.

Saffloflavonesides A and B, two rearranged derivatives of flavonoid C-glycosides with a furan-tetrahydrofuran ring from Carthamus tinctorius.

Two new rearranged derivatives of flavonoid C-glycosides, saffloflavonesides A (1) and B (2), were isolated from the florets of Carthamus tinctorius. Their structures were determined using UV, IR, HRESIMS, and 1D and 2D NMR data and by comparing experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1 and 2 were unprecedented chalcone and flavanone derivatives possessing a furan conjoining tetrahydrofuran ring. A potential biosynthetic pathway was proposed. At 10 μM, 1 and 2 both showed strong inhibitory activity against PC12 cell damage induced by rotenone.

Flavone C-glycosides from Capsicum annuum L.: relationships between antioxidant activity and lipophilicity

Three flavonoid C-glycosides isolated from pepper fruit (Capsicum annuum L.), var. Capel Hot (luteolin 6-C-glucoside, luteolin 6,8-di-C-glucoside and apigenin 6-C-glucoside-8-C-arabinoside), were investigated to determine their antioxidant activity and lipophilicity. The antioxidant activity was evaluated using in vitro methods to generate free radicals in hydrophilic (superoxide radical) and lipophilic (2,2-diphenyl-1-picrylhydrazyl (DPPH) and peroxide radicals) media. Parameters characterising the lipophilicity (log P) of the studied compounds were calculated using three commonly available software programs. The relationships between the calculated log P of the investigated compounds and the experimentally determined antioxidant activities are discussed. The chemical activity of the flavonoid C-glycosides and aglycones was variable depending on the type of assay used. Luteolin and its C-6 glucoside showed the greatest ability to scavenge superoxide radicals (generated in the enzymatic and non-enzymatic systems) and DPPH radicals and also had the strongest activity in inhibiting xanthine oxidase activity, followed by apigenin-C-glycoside and apigenin. A high positive correlation coefficient was found between the ability of tested C-glycosides to inhibit xanthine oxidase and the calculated log P values. The highest correlation coefficient was obtained for the ACD/log P (Advanced Chemistry Development, Inc.) method (R = 0.790). In contrast, negative correlations were obtained between the abilities to scavenge superoxide, DPPH and lipid peroxyl radicals. The highest negative correlation coefficient was obtained in a β-carotene/linoleic acid model system and the Ghose–Crippen method (R = −0.725).

Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts

The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts (AME). In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride (CCl4)-induced hepatitis in mice, D-galactosamine (D-GalN)-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.

ChemInform Abstract: Glycosylation Reactions in the Synthesis of Flavonoid Glycosides

AbstractReview: [82 refs.

Protective effect of total flavonoid C-glycosides from Abrus mollis extract on lipopolysaccharide-induced lipotoxicity in mice

Abrus mollis is a widely used traditional Chinese medicine for treating acute and chronic hepatitis, steatosis, and fibrosis. It was found that the total flavonoid C-glycosides from Abrus mollis extract (AME) showed potent antioxidant, anti-inflammatory, and hepatoprotective activities. To further investigate the hepatoprotective effect of AME and its possible mechanisms, lipopolysaccharide (LPS)-induced liver injury models were applied in the current study. The results indicated that AME significantly attenuated LPS-induced lipid accumulation in mouse primary hepatocytes as measured by triglyceride (TG) and total cholesterol (TC) assays and Oil Red O staining. Meanwhile, AME exerted a protective effect on LPS-induced liver injury as shown by decreased liver index, serum aminotransferase levels, and hepatic lipid accumulation. Real-time PCR and immunoblot data suggested that AME reversed the LPS-mediated lipid metabolism gene expression, such as sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1). In addition, LPS-induced overexpression of activating transcription factor 4 (ATF4), X-box-binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP) were dramatically reversed by AME. Furthermore, AME also decreased the expression of LPS-enhanced interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). Here, it is demonstrated for the first time that AME ameliorated LPS-induced hepatic lipid accumulation and that this effect of AME can be attributed to its modulation of hepatic de novo fatty acid synthesis. This study also suggested that the hepatoprotective effect of AME may be related to its down-regulation of unfolded protein response (UPR) activation.

Flavonoid C-glycosides from pigeon pea leaves as color and anthocyanin stabilizing agent in blueberry juice

The influences of flavonoid C-glycoside extracts from pigeon pea leaves (FCGE) and its main components vitexin and orientin on the color and anthocyanins stability of blueberry juice were investigated in the thermal experiments. The color of juice was enhanced by FCGE and its main components in a molar ratio of 1:1 (anthocyanins/copigment). The saturated color of juice with FCGE and its main components could hold for a significantly longer time. Additionally, copigment FCGE, vitexin and orientin significantly enhanced the stability of anthocyanins. Half-life of anthocyanins in juice samples with FCGE (1:1), orientin and vitexin increased 87%, 79%, and 62%, respectively. These results indicated FCGE showed dramatic effect on the color and anthocyanins stability of juice. Furthermore, juice samples with copigments possessed higher total phenolics content and higher DPPH radical-scavenging activity. Therefore, natural, easily available, inexpensive FCGE has potential as color enhancer and anthocyanins stabilizer in food industry.

Glycosylation Reactions in the Synthesis of Flavonoid Glycosides

An overview of flavonoid glycoside synthesis has been provided with an emphasis on the construction of the glycosidic linkages. 1 Introduction 2 Synthetic Tactics 3 Synthesis of Flavonoid O-Glycosides 3.1 Glycosylation with Glycosyl Bromides 3.2 Glycosylation with Glycosyl Imidates 3.3 Glycosylation with Glycosyl Esters 3.4 Glycosylation with Glycosyl Fluorides 3.5 Combined Application of Different Types of Glycosyl Donors­ 4 Synthesis of Flavonoid C-Glycosides 5 Synthesis of Flavonoid Mixed O,C-Glycosides 6 Conclusion

Bioactive phenolics of fresh and freeze-dried sweet and semi-spicy pepper fruits (Capsicum annuum L.)

Changes in contents of eight phenolic compounds in extracts from fresh and freeze-dried placentas and pericarps of four cultivars of pepper fruit (Capsicum annuum) were investigated. These compounds comprised two phenolic acid derivatives, four flavonoid O-glycosides, and two flavonoid C-glycosides. Quantitative HPLC–DAD analysis was performed on the basis of the peak area of standards isolated from pepper and identified by MS/MS2 analysis. The main compounds in the pericarp were quercetin O-glycosides, while trans-p-feruloyl-β-d-glucopyranoside predominated in the placenta, at a concentration almost 10 times higher than that in the pericarp. In general, lower levels of phenolic acid derivatives were found in extracts from lyophilised fruits, but different directions of changes in the concentrations of flavonoid O- and C-glycosides from fresh and freeze-dried fruits were noted. The antioxidant activity measured by the DPPH method was higher for samples of fresh fruits than for freeze-dried samples. Additionally, the antioxidant activities of extracts from placentas correlated well with the changes in flavonoid C-glycosides (R2=0.63), while the antioxidant activities from the pericarp correlated with changes in phenolic acid derivatives (R2=0.78).

Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice

Spinosin is a C-glycoside flavonoid isolated from the seeds of Zizyphus jujuba var. spinosa. This study investigated the effect of spinosin on cholinergic blockade-induced memory impairment in mice. Behavioral tests were conducted using the passive avoidance, Y-maze, and Morris water maze tasks to evaluate the memory-ameliorating effect of spinosin. Spinosin (10 or 20mg/kg, p.o.) significantly ameliorated scopolamine-induced cognitive impairment in these behavioral tasks with a prolonged latency time in the passive avoidance task, an increased percentage of spontaneous alternation in the Y-maze task and a lengthened swimming time in target quadrant in the Morris water maze task. In addition, a single administration of spinosin in normal naïve mice also enhanced the latency time in the passive avoidance task. To identify the mechanism of the memory-ameliorating effect of spinosin, receptor antagonism analysis and Western blotting were performed. The ameliorating effect of spinosin on scopolamine-induced memory impairment was significantly antagonized by a sub-effective dose (0.5mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)tetralin, a 5-HT1A receptor agonist. In addition, spinosin significantly increased the expression levels of phosphorylated extracellular signal-regulated kinases and cAMP response element-binding proteins in the hippocampus. Taken together, these results indicate that the memory-ameliorating effect of spinosin may be, in part, due to the serotonergic neurotransmitter system, and that spinosin may be useful for the treatment of cognitive dysfunction in diseases such as Alzheimer's disease.

Experimental and theoretical investigations on the antioxidant activity of isoorientin from Crotalaria globosa

The increasing interests in naturally occurring flavonoids are well known for their bioactivity as antioxidants. The present investigations with combined experimental and theoretical methods are employed to determine the radical scavenging activity and phytochemicals present in Crotalaria globosa, a novel plant source. Preliminary quantification of ethanolic extract of leaves shows high phenolic and flavonoid content than root extract; also it is validated through DPPH assay. Further analysis is carried out with successive extracts of leaves of varying polarity of solvents. In DPPH and FRAP assays, ethyl acetate fraction (EtOAc) exhibit higher scavenging activity followed by ethanol fraction (EtOH) whereas in NOS assay ethanol fraction is slightly predominant over the EtOAc fraction. The LC–MS analysis provides tentative information about the presence of flavonoid C-glycoside in EtOAc fraction (yellow solid). Presence of flavonoid isorientin has been confirmed through isolation (PTLC) and detected by spectroscopy methods (UV–visible and 1HNMR). Utilizing B3LYP/6-311G (d,p) level of theory the structure and reactivity of flavonoid isoorientin theoretically have been explored. The analysis of the theoretical Bond dissociation energy values, for all OH sites of isoorientin reveals that minimum energy is required to dissociate H-atom from B-ring than A and C-rings. In order to validate the antioxidant characteristics of isoorientin the relevant molecular descriptors IP, HOMO–LUMO, Mulliken spin density analysis and molecular electrostatic potential surfaces have been computed and interpreted. From experimental and theoretical results, it is proved that isoorientin can act as potent antiradical scavenger in oxidative system.

Identification of a Bifunctional Maize C- and O-Glucosyltransferase

Flavonoids accumulate in plant vacuoles usually as O-glycosylated derivatives, but several species can also synthesize flavonoid C-glycosides. Recently, we demonstrated that a flavanone 2-hydroxylase (ZmF2H1, CYP93G5) converts flavanones to the corresponding 2-hydroxy derivatives, which are expected to serve as substrates for C-glycosylation. Here, we isolated a cDNA encoding a UDP-dependent glycosyltransferase (UGT708A6), and its activity was characterized by in vitro and in vivo bioconversion assays. In vitro assays using 2-hydroxyflavanones as substrates and in vivo activity assays in yeast co-expressing ZmF2H1 and UGT708A6 show the formation of the flavones C-glycosides. UGT708A6 can also O-glycosylate flavanones in bioconversion assays in Escherichia coli as well as by in vitro assays with the purified recombinant protein. Thus, UGT708A6 is a bifunctional glycosyltransferase that can produce both C- and O-glycosidated flavonoids, a property not previously described for any other glycosyltransferase.

Flavonoids from Tetrastigma obtectum enhancing glucose consumption in insulin-resistance HepG2 cells via activating AMPK

Four new flavonoids including three C-glycosidic flavonoids, named tetrastigma A–D (1–4) and five known flavones (5–9) were isolated from the herbs of Tetrastigma obtectum (Wall.) Planch. The structures of 1–4 were elucidated by 1D- and 2D-NMR and HR mass spectrometric methods. Compound 1 caused significant enhancement in glucose consumption by insulin-resistant HepG2 cells compared with control cells. In addition, compound 1 stimulated phosphorylation of AMPK, which plays an important role in glycometabolism.

New spinosin derivatives from the seeds of Ziziphus mauritiana

Three new acylated flavonoid C-glycosides, 6‴-(-)-phaseoylspinosin (1), 6‴-(3″″,4″″,5″″-trimethoxyl)-(E)-cinnamoylspinosin (2), and 6‴-(4″″-O-β-D-gluco-pyranosyl)-benzoylspinosin (3), were isolated from the seeds of Ziziphus mauritiana (Rhamnaceae). A further 19 known compounds including eight spinosin analogues (4–11) were also isolated. Their structures were elucidated by means of spectroscopic analysis and chemical method. Among spinosin derivatives 1, 2, 4, 7, 8, and triterpenoid saponin 14, jujuboside A (14) displayed moderate acetylcholinesterase (AchE) inhibitory activity with an inhibition value of 46.2% at a concentration of 1 µM. Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007/s13659-013-0028-5 and is accessible for authorized users.

A New Flavonoid C-Glycoside from Solanum elaeagnifolium with Hepatoprotective and Curative Activities against Paracetamol- Induced Liver Injury in Mice

A new flavonoid C-glycoside, kaempferol 8-C-beta-galactoside, along with twelve known glycosidic flavonoids was isolated from the aqueous methanolic extract of Solanum elaeagnifolium Cav. (Solanaceae), by conventional chromatographic methods; their structure elucidation was achieved using UV, ESI-MS, and NMR spectral analyses. Groups of six mice were administered S. elaeagnifolium extracts at 25, 50, and 75 mg/kg body weight (BW) prior to or post administration of a single dose of paracetamol (500 mg/kg BW). The extract showed significant hepatoprotective and curative effects against histopathological and histochemical damage induced by paracetamol in liver. The extract also ameliorated the elevation in glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), and alkaline phosphatase (ALP) levels. These findings were accompanied by a nearly normal architecture of the liver in the treated groups, compared to the paracetamol control group. As a positive control, silymarin was used, an established hepatoprotective drug against paracetamol-induced liver injury. This study provides the first validation of the hepatoprotective activity of S. elaeagnifolium.

The Passiflora tripartita (Banana Passion) Fruit: A Source of Bioactive Flavonoid C-Glycosides Isolated by HSCCC and Characterized by HPLC–DAD–ESI/MS/MS

The banana passion fruit (Passiflora tripartita Breiter, Passifloraceae) known as “tumbo” is very appreciated in tropical and subtropical countries of South America. Methanolic extracts from peel and the fruit juice of P. tripartita growing in Chile were analyzed for antioxidant capacity as well as for flavonoid and phenolic content. A chromatographic method was developed for the rapid identification of the main phenolics in the samples by HPLC-DAD and HPLC-MS. The fast fingerprint analysis allowed the detection of eighteen flavonoid C-glycosides and four flavonoid O-glycoside derivatives which were characterized by UV spectra and ESI-MS-MS analysis. Several of the C-glycosides detected are structurally related to the orientin derivative 4′-methoxy-luteolin-8-C-(6″acetyl)-β-D-glucopyranoside (31), fully elucidated by spectroscopic methods. The antioxidant derivative 31 along with schaftoside, vicenin II, orientin and vitexin were isolated from the fruit extract by high-speed countercurrent chromatography (HSCCC). A suitable method for the preparative isolation of flavonol C-glycosides from “tumbo” extracts by HSCCC is reported. The pulp of the fruits showed good antioxidant capacity (12.89 ± 0.02 μg/mL in the DPPH assay). The peel presented the highest content of flavonoids (56.03 ± 4.34 mg quercetin/100 g dry weight) which is related to the highest antioxidant power (10.41 ± 0.01 μg/mL in the DPPH assay).

Review on Sphaeranthus indicus Linn. (Koṭṭaikkarantai)

Sphaeranthus indicus Linn. is from the aroma family Asteraceae. It is also known with other synonyms such as Munditika, Mundi, Shravana, Bhikshu, Tapodhana, Mahashravani, Shravanahva, Shravanashirshaka. It is abundantly distributed in damp areas in plains and also as a weed in the rice fields. In the Indian system of medicine, the plant as a whole plant or its different anatomical parts viz., leaf, stem, bark, root, flower and seed are widely used for curing many diseases. The plant is bitter, stomachic, restorative, alterative, pectoral, demulcent and externally soothing. The whole plant and its anatomical parts have been reported with different types of secondary metabolites which include eudesmanolides, sesquiterpenoids, sesquiterpene lactones, sesquiterpene acids, flavone glycosides, flavonoid C-glycosides, isoflavone glycoside, sterols, sterol glycoside, alkaloid, peptide alkaloids, amino acids and sugars. The essential oils obtained from the flowers and whole plants were analyzed by different authors and reported the presence of many monoterpene hydrocarbons, oxygenated monoterpenes, sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The whole plants, its isolated secondary metabolites and different anatomical parts have been reported for ovicidal, antifeedant, anthelmintic, antimicrobial, antiviral, macrofilaricidal, larvicidal, analgesic, antipyretic, hepatoprotective, antitussive, wound healing, bronchodilatory, mast cell stabilizing activity, anxiolytic, neuroleptic, immunomodulatory, anti-diabetic, antihyperlipidemic and antioxidant, antioxidant, central nervous system depressant, anti-arthritic, nephroprotective, anticonvulsant activities and many other activities. It is also effective on psoriasis. In the present paper, the plant is reviewed for its phytochemical and pharmacological reports in detail.

A New Flavonoid C-Glycoside from Solanum elaeagnifolium with Hepatoprotective and Curative Activities against Paracetamol-Induced Liver Injury in Mice

A New Flavonoid C-Glycoside from Solanum elaeagnifolium with Hepatoprotective and Curative Activities against Paracetamol-Induced Liver Injury in Mice

Phytochemical analyses of Ziziphus jujuba Mill. var. spinosa seed by ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry

Ziziphus jujuba Mill. var. spinosa (Z. jujuba) seeds have attracted much attention within the field of medicine due to their significant effects against disturbances of the central nervous system. Secondary metabolites composition is key to the influence of the pharmaceutical and commercial qualities of this plant. In this work, the phytochemical profile of Z. jujuba seeds was analysed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS). The UPLC-MS/MS information identified the main secondary metabolites in Z. jujuba seeds, including flavonoid C-glycosides, triterpene acids and unsaturated fatty acids. The leading chemical identified by UPLC-MS/MS was betulinic acid, and oleic acid was the leading volatile from the GC-MS results. All the samples tested showed similar phytochemical profiles, but levels of the chemical compounds varied. Principal component analysis revealed the principal secondary metabolites that could define the differences in quality. It was confirmed that the combination of UPLC-MS/MS and GC-MS was an effective technique to demonstrate the pharmaceutical quality of Z. jujuba seeds.

A comparison of C-glycosidic flavonoid isomers by electrospray ionization quadrupole time-of-flight tandem mass spectrometry in negative and positive ion mode

Flavonoid C-glycosides are important bioactive natural compounds. They often occur as 6-C and 8-C isomers, which makes the structural elucidation difficult. In this paper, the high resolution electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI Q-TOF MS/MS) was employed to distinguish two pairs of isomeric C-glycosidic flavonoids, isoorientin (luteolin-6-C-glucoside), orientin (luteolin-8-C-glucoside), isovitexin (apigenin-6-C-glucoside), and vitexin (apigenin-8-C-glucoside), in negative and positive ion mode with different collision energy (collision-induced dissociation, CID). The two pairs of isomers can be distinguished via product ion mass spectra (MS/MS) of precursor ion [M−H]− and [M+H]+. The results demonstrated that these diagnostic characteristic ions used to identify the differences between 6-C and 8-C isomers were as follows: the product ions [M−H−H2O]−, [0,3X0−H]− and [0,3X0−H−H2O]− in product ion mass spectra (MS/MS) of precursor ion [M−H]− in negative ion mode, the product ions [M+H−4H2O]+, [0,3X0+3H−2H2O]+, [0,4X0+H−H2O]+, [M+H−H2O]+, [M+H−2H2O]+, [M+H−3H2O]+, [0,2X0+H]+, [0,1X0+H]+ and [0,4X0+H−2H2O]+ in product ion mass spectra (MS/MS) of precursor ion [M+H]+ in positive ion mode.