Beyerene derivatives and other constituents from Petunia patagonica

Two new diterpenes of the beyerene type, ent-19-hydroxy-1 7-acetoxybeyer-15-ene and ent-beyer-15-en-17-oic acid, and two previously characterized kauranoids, ent-16β-hydroxy-17-acetoxykaurane and ent-16β,1 7-dihydroxy-kaurane, as well as two known flavonoids, luteolin-7,3′,4′-trimethyl ether and luteolin-7,3′-dimethyl ether, and a triterpenoid, oleanoic acid, were obtained from a chloroform extract of Petunia patagonica. The new structures were elucidated by spectral data and chemical transformations.     

Iridoid and megastigmane glycosides from Phlomis aurea

From the leaves of Phlomis aurea, two new iridoids of unique structures named 3-epiphlomurin (1) and phlomurin (2), a new megastigmane glucoside phlomuroside (3) and a new benzyl alcohol glycoside having the structure benzyl alcohol-O-beta-xylopyranosyl-(1-->2)-beta-glucopyranoside (4) have been isolated together with four known iridoids auroside, lamiide, 8-epiloganin and ipolamiide, two known phenolic glycosides acteoside (verbascoside) and syringin, one known phenylethanoid glycoside 2-phenylethyl-O-beta-xylopyranosyl-(1-->2)-beta-glucopyranoside, one known lignan liriodendrin and three known flavonoids chrysoeriol-7-O-beta-glucopyranoside, acacetin-7-O-beta-glucopyranoside and luteolin-7-O-beta-glucopyranoside. The structures of the isolated compounds were verified by means of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectral analyses.     

Phenolic glycosides from Phagnalon rupestre

Analysis of the butanol-soluble fraction from the methanolic extract of the aerial parts of Phagnalon rupestre (Asteraceae) has led to the isolation of seven phenolic compounds. Three have been identified on the basis of their NMR spectra as new natural compounds: the lignan 7,7'-bis-(4-hydroxy-3,5-dimethoxyphenyl)-8,8'-dihydroxymethyl-tetrahydrofuran-4-O-beta-glucopyranoside (1), the prenylhydroquinone glycoside 1-O-beta-glucopyranosyl-1,4-dihydroxy-2-(3'-hydroxy-3'-methylbutyl) benzene (2) and the acetophenone glycoside 12-O-beta-glucopyranosyl-9beta,12-dihydroxytremetone (3). The known flavonoids apigenin-7-O-beta-glucoside, luteolin-7-O-beta-glucoside, luteolin-7-O-beta-glucuronide and the acetophenone picein were also isolated.     

Development of an HPLC-PAD-MS assay for the identification and quantification of major phenolic edelweiss (Leontopodium alpium Cass.) constituents

The analytical assessment of edelweiss (Leontopodium alpinum) herb extracts, used in traditional alpine medicine, has resulted in the development of a HPLC-PAD-MS method that allows baseline separation of almost all constituents. Peak assignment of 14 analytes was achieved by comparison of retention times, UV and mass spectra with those of reference compounds either commercially available (luteolin, apigenin and chlorogenic acid) or isolated from edelweiss plants by column chromatography. Ten of the isolated analytes were identified as the known natural products: quercetin-3-O-beta-D-glucoside, luteolin-7-O-beta-D-glucoside, luteolin-3'-O-beta-D-glucoside, luteolin-4'-O-beta-D-glucoside, apigenin-7-O-beta-D-glucoside, 6-hydroxy-luteolin-7-O-beta-D-glucoside, luteolin-7,4'-di-O-beta-D-glucoside, chrysoeriol-7-O-beta-D-glucoside, leontopodic acid and 3,5-dicaffeolyquinic acid. One analyte, 3,4,5-tri-(E)-caffeoly-D-glucaric acid proved to be a new natural product and was named leontopodic acid B. Structure elucidation was carried out by means of MS and NMR spectroscopy in all cases. The aerial plant parts of L. alpinum (capitula, inflorescence leaves, stems, stem leaves and leaves of the basal rosette) showed variable amounts of the above-mentioned constituents, although qualitative differences were not observable.     

Flavonoids from Achillea nobilis L

The detailed investigation of a methanolic extract of aerial parts of Achillea nobilis resulted in the isolation of 10 flavonoids. A new C-glycosylflavone, luteolin-6-C-apiofuranosyl-(1'-->2')-glucoside, was isolated besides orientin, isoorientin, vitexin, isoschaftoside, luteolin-7-O-beta-glucuronide, luteolin-4'-O-beta-glucoside and quercetin-3-O-methyl ether and two rare flavonolglycosides, quercetin-3-O-alpha-arabinosyl-(1'-->6')-glucoside and quercetin-3-O-methylether-7-O-beta-glucoside. The structures were established either by comparison with authentic substances or by UV, 1H NMR and 13C NMR spectroscopic methods including 2D-NMR techniques and ESI-MS.     

The inhibitory effect of luteolin-7-O-glucoside on the formation of pentyl and 7-carboxyheptyl radicals from 13-hydroperoxy-9,11-octadecadienoic acid in the presence of iron(II) ions

A flavone glucoside, luteolin-7-O-glucoside (luteolin-7-G) inhibited the formation of pentyl and 7-carboxyheptyl radicals in the reaction of 13-hydroperoxy-9,11-octadecadienoic (13-HPODE) acid with iron(II) ions. The inhibitory effect of luteolin-7-G was diminished in the presence of EDTA. These results indicated that the inhibitory effects of luteolin-7-G occur partly through the chelation of iron ions. Measurement of visible spectra also showed that luteolin-7-G chelates iron ions. On the other hand, luteolin-7-G did not inhibit the reaction under anaerobic conditions, suggesting that oxygen molecules participate in the inhibition. Oxygen consumption measurements showed that the luteolin-7-G/iron ion complexes react with oxygen molecules in competition with 13-HPODE acid, and free iron ions exclusively react with 13-HPODE acid. The reaction of luteolin-7-G/iron ion complexes with oxygen molecules possibly diminishes the formation of pentyl and 7-carboxyheptyl radicals.     

Studies on the Flavonoids of Dracocephalum integrifolium Bge

From EToAc extracts of over-ground parts of Dracocephalum integrifolium Bge, 2 flavonoide compounds, were isolated and identified as luteolin-7-O-β-D-glucopyrano-side and luteolin-7-O-glucuronide by their chemical studies and spectral analysis.     

Studies on the Chemical Constituents of Elsholtzia eriostachya Benth.

Sixteen constituents were isolated from the hot alcohoic extract of the whole plant of a Chinese medicinal herb Elsholtzia eriostachya Benth.. Twelve of them were elucidated by spectroscopic and chemical evidences as follows: dotriacontanoic acid （l）, β-sitosterol（2）, succinic acid （3）, aretigenin (5), 3-hydroxyarctiin （7）, luteolin-5-O-β-D-glucoside （8）, luteolin-7-O-β-D-glucoside (9), gentisic acid -5-O-β-D-glucopranoside (10), hyperoside (11), morin-7-O-β-D-glucopranoside （12）, isoskuranetin-7-O-β-D-neohesperidoside （14）, acacetin-7-O-β-D-rutinoside （15） 7 is a new compound, and eight compounds (3, 5, 8, 10,11,12,14 and 15) were isolated from Elsholtzia for the first time.     

Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW264.7 cells

Both reactive oxygen- and nitrogen-derived reactive species play important roles in physiological and pathophysiological conditions. Flavones, luteolin and luteolin-7-O-glucoside along with a rich plant source of both flavones, namely dandelion (Taraxacum officinale) flower extract were studied for antioxidant activity in different in vitro model systems. In this current study, luteolin and luteolin-7-O-glucoside at concentrations lower than 20 microM, significantly (p < 0.05) suppressed the productions of nitric oxide and prostaglandin E2 (PGE2) in bacterial lipopolysaccharide activated-mouse macrophage RAW264.7 cells without introducing cytotoxicity. The inhibitory effects were further attributed to the suppression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression, and not reduced enzymatic activity. Similar suppression for both inducible enzymes was also found with the presence of dandelion flower extract, specifically, the ethyl acetate fraction of dandelion flower extract which contained 10% luteolin and luteolin-7-O-glucoside.     

A new hepatoprotective flavone glycoside from the flowers of Onopordum alexandrinum growing in Egypt

A bioactivity-guided fractionation of the ethyl acetate fraction of the flowers of Onopordum alexandrinum L. (Asteraceae) yielded a new flavonoidal glycoside designated as acacetin-7-O-galacturonide (9), alongside with nine known flavonoids; 6-methoxy-apigenin (hispidulin) (1), acacetin (2), apigenin (3), luteolin (4), kaempferol (5), eriodictyol (6), apigenin-7-O-glucoside (7), luteolin-7-O-glucoside (8), and kaempferol-3-O-rutinoside (10). The compounds were assayed for their hepatoprotective activity against CCl4-induced hepatic cell damage in rats and free radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds 4, 6, 9, and 10 have not been previously reported from flowers of O. alexandrinum L., and this is the first report of acacetin-7-O-galacturonide (9) in nature which has also shown significant hepatoprotective and free radical scavenging effects. The isolated compounds were identified using different spectroscopic methods (UV, 1H NMR, 13C NMR, HMQC, HMBC, and COSY).     

Two major flavonoids from Ballota nigra

Two lactoylate flavonoids, luteolin-7-lactate and luteolin-7-glucosyl-lactate were isolated from Ballota nigra. They should be used for the chemical standardization of this drug of medicinal interest.     

崇左金花茶花朵和叶片类黄酮UPLC-Q-TOF-MS分析

以崇左金花茶（Camellia chuangtsoensis）为材料,利用超高效液相色谱-四极杆-飞行时间质谱（UPLC-Q-TOF-MS）联用技术定性定量分析其花朵（花瓣、雄蕊）和叶片（老叶、新叶）中类黄酮成分与含量。结果表明,崇左金花茶中共检测到14种类黄酮成分,木犀草素、木犀草素-7-O-芸香糖苷、槲皮素-3,7-O-二葡萄糖苷、芸香柚皮苷、圣草素和染料木苷为山茶属金花茶组植物中首次发现,其中槲皮素-3,7-O-二葡萄糖苷、芸香柚皮苷、圣草素和染料木苷主要存在于花朵中,木犀草素和木犀草素-7-O-芸香糖苷在花朵中含量高于叶片,雄蕊中高于花瓣;槲皮素-3-O-葡萄糖苷、槲皮素-7-O-葡萄糖苷、槲皮素-3-O-芸香糖苷和山柰酚-3-O-葡萄糖苷为金花茶组植物叶片中首次发现,其叶片中含量远低于花朵,老叶中远低于新叶,雄蕊中远低于花瓣;儿茶素和表儿茶素在花朵中含量高于叶片,雄蕊中高于花瓣;槲皮素和山萘酚在花朵和叶片中含量均较低。崇左金花茶花瓣和雄蕊中含量较高的类黄酮为儿茶素类、木犀草素类和槲皮素类,主要是表儿茶素、木犀草素和槲皮素-3-O-葡萄糖苷;叶片中为儿茶素类和木犀草素类,主要是表儿茶素、木犀草素和木犀草素-7-O-芸香糖苷。崇左金花茶花瓣和雄蕊中儿茶素类、木犀草素类及类黄酮总量均高于叶片,且雄蕊高于花瓣;花瓣和雄蕊中槲皮素类远高于叶片,且花瓣中远高于雄蕊。     

Antiradical and anti-H2O2 properties of polyphenolic compounds from an aqueous peppermint extract

Polyphenolic compounds such as eriocitrin, luteolin-7-O-rutinoside, diosmin, hesperidin, narirutin, isorhoifolin, rosmarinic and caffeic acids were identified in an aqueous extract (Ex) obtained from peppermint leaves (Menthae x piperitae folium). The content of polyphenols in Ex was as follows: eriocitrin 38%, luteolin-7-O-rutinoside 3.5%, hesperidin 2.9%, diosmin 0.8%, isorhoifolin 0.6%, narirutin 0.3%, rosmarinic acid 3.7% and caffeic acid 0.05%. The strongest antiradical activity (determined as DPPH* scavenging features) was observed for luteolin-7-O-rutinoside, eriocitrin and rosmarinic acid. Caffeic acid and hesperidin revealed a lower antiradical activity while isorhoifolin, narirutin and diosmin showed the lowest activity. The strongest anti-H2O2 activity was observed for eriocitrin, a little lower for rosmarinic acid. The rate of hydrogen peroxide scavenging activity displayed by luteolin-7-O-rutinoside and caffeic acid was lower than that of rosmarinic acids. Hesperidin appeared to be a very weak scavenger of hydrogen peroxide. Almost no anti-H2O2 activity was demonstrated for diosmin, narirutin and isorhoifolin. Among examined flavonoids, the strongest antiradical and anti-H2O2 activity was shown for compounds with two hydroxy groups bound to the Bring in ortho position in relation to each other. Replacement of one hydroxy group in the Bring with a methoxy group or removing one hydroxy group leads to decrease of antiradical and anti-H2O2 activity of flavonoids. Our results suggest that eriocitrin is a powerful peppermint antioxidant and a free radical scavenger.     

Flavon- and flavonolglycosides from Achillea pannonica Scheele

The detailed investigation of a methanolic extract of aerial parts of Achillea pannonica SCHEELE. within a chemotaxonomic study led to the isolation of 6 flavonoid glycosides. Besides rutin, apigenin-7-O-glucopyranoside, luteolin-7-O-glucopyranoside, apigenin-7-O-rutinoside and acacetin-7-O-rutinoside, an unusual flavondiglucoside was isolated. Its structure was established by UV, 1H NMR and 13C NMR spectroscopic methods including 2D-NMR techniques and ESI-MS as luteolin-7,4'-O-beta-diglucoside. This substance is reported for the first time in the genus Achillea. Chemotaxonomic aspects are discussed briefly.     

Biosynthesis of a water solubility-enhanced succinyl glucoside derivative of luteolin and its neuroprotective effect

The natural flavonoids luteolin and luteoloside have anti-bacterial, anti-inflammatory, anti-oxidant, anti-tumour, hypolipidemic, cholesterol lowering and neuroprotective effects, but their poor water solubility limits their application in industrial production and the pharmaceutical industry. In this study, luteolin-7-O-β-(6″-O-succinyl)-d -glucoside, a new compound that was prepared by succinyl glycosylation of luteolin by the organic solvent tolerant bacterium Bacillus amyloliquefaciens FJ18 in an 8.0% DMSO (v/v) system, was obtained and identified. Its greater water solubility (2293 times that of luteolin and 12 232 times that of luteoloside) provides the solution to the application problems of luteolin and luteoloside. The conversion rate of luteolin (1.0 g l⁻¹) was almost 100% at 24 h, while the yield of luteolin-7-O-β-(6″-O-succinyl)-d -glucoside reached 76.2%. In experiments involving the oxygen glucose deprivation/reoxygenation injury model of mouse hippocampal neuron cells, the cell viability was significantly improved with luteolin-7-O-β-(6″-O-succinyl)-d -glucoside dosing, and the expressions of the anti-oxidant enzyme HO-1 in the nucleus increased, providing a neuroprotective effect for ischemic cerebral cells. The availability of biosynthetic luteolin-7-O-β-(6″-O-succinyl)-d -glucoside, which is expected to replace luteolin and luteoloside, would effectively expand the clinical application value of luteolin derivatives.     

Flavonoids from Dracocephalum tanguticum and their cardioprotective effects against doxorubicin-induced toxicity in H9c2 cells

Two new flavonoids, ladanetin-6-O-β-(6″-O-acetyl)glucoside (1) and pedalitin-3'-O-β-glucoside (2), together with 15 known compounds (3-17), were isolated from the whole plants of Dracocephalum tanguticum. Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by the comparison with spectroscopic data reported in the literature. Antioxidant capacities of the isolated substances were determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferrous ions, and ABTS(·)(+) radical in vitro assay, and their cytoprotective activities were also tested on doxorubicin (DOX)-induced toxicity in H9c2 cardiomyocytes. Among all the tested compounds, luteolin-7-O-β-D-glucopyranoside (7) exhibited both strong antioxidative effect and high protective activity against DOX-induced toxicity. Further investigation found 7 could decrease DOX-induced death of H9c2 cell, reduce LDH and CK level, and inhibit the elevated intracellular concentration of ROS and [Ca(2+)](i). The preliminary structure-activity relationships (SAR) of these compounds revealed the Δ(2,3) double bond on C-ring and 3',4'-di-OHs on B-ring with a flavone skeleton such as luteolin and its derivatives, were necessary for their cardioprotective effects.     

Choleretic effects of yarrow (Achillea millefolium s.l.) in the isolated perfused rat liver

Different species from the Achillea millefolium aggregate are used against gastrointestinal and hepato-biliary disorders in traditional European medicine. In this work, a fraction enriched in dicaffeoylquinic acids (DCCAs) and luteolin-7-O-β-d-glucuronide was investigated on its choleretic effect in the isolated perfused rat liver (IPRL) compared to cynarin (1,3-DCCA), the main choleretic compound of Cynara scolymus L. A fraction containing 3,4-, 3,5- and 4,5-DCCA and luteolin-7-O-β-d-glucuronide was prepared by solid phase extraction from a 20% methanolic extract of yarrow. A total amount of 48.8% DCCAs and 3.4% luteolin-7-O-β-d-glucuronide was determined by HPLC analysis with cynarin as internal standard. IPRL experiments revealed a dose-dependant increase in bile flow (23–44–47%) by the Achillea fraction. Choleresis was two- to three-fold higher than that of cynarin. The combined effect of DCCAs and luteolin-7-O-β-d-glucuronide stimulated bile flow more effectively than the single compound cynarin. Due to their polar structure, these compounds are quantitatively extracted into teas and tinctures; hence, they seem to be the choleretic active principles in the traditional application forms of yarrow.     

Deoxypodophyllotoxin content and antioxidant activity of aerial parts of Anthriscus sylvestris Hoffm

Deoxypodophyllotoxin content of the aerial parts of Anthriscus sylvestris Hoffm. growing at different altitudes was evaluated in comparison to the roots. The lignan accumulation in ground parts was at least double compared to aerial ones. In addition antioxidant-guided fractionation of the crude methanol extract of aerial parts was performed with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Active fractions contained mainly luteolin-7-O-glucoside and chlorogenic acid. Antioxidant properties of both crude extract and isolated compounds were also investigated with the Briggs-Rauscher (BR) oscillating reaction. A satisfactory agreement between the results obtained with the two methods was observed.     

Leuconostoc mesenteroides glucansucrase synthesis of flavonoid glucosides by acceptor reactions in aqueous-organic solvents

The enzymatic glucosylation of luteolin was attempted using two glucansucrases: the dextransucrase from Leuconostoc mesenteroides NRRL B-512F and the alternansucrase from L. mesenteroides NRRL B-23192. Reactions were carried out in aqueous-organic solvents to improve luteolin solubility. A molar conversion of 44% was achieved after 24h of reaction catalysed by dextransucrase from L. mesenteroides NRRL B-512F in a mixture of acetate buffer (70%)/bis(2-methoxyethyl) ether (30%). Two products were characterised by nuclear magnetic resonance (NMR) spectroscopy: luteolin-3'-O-alpha-d-glucopyranoside and luteolin-4'-O-alpha-d-glucopyranoside. In the presence of alternansucrase from L. mesenteroides NRRL B-23192, three additional products were obtained with a luteolin conversion of 8%. Both enzymes were also able to glucosylate quercetin and myricetin with conversion of 4% and 49%, respectively.     

Screening of various phenolic acids and flavonoid derivatives for their anticholinesterase potential

Alzheimer's disease (AD), the most common form of dementia, is a neurodegenerative disease characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioural changes. The oldest, on which most currently available drug therapies are based, is known as the "cholinergic hypothesis" and suggests that AD begins as a deficiency in the production of the neurotransmitter acetylcholine. Therefore, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors have gained a great popularity for the treatment of AD. In this study, we screened in vitro inhibitory activities of a number of phenolic acids (chlorogenic, caffeic, gallic, and quinic acids) as well as of various flavonoid derivatives (genistein, biochanin A, naringin, apigenin, quercetin, luteolin-7-O-rutinoside, kaempferol-3-O-galactoside, diosmin, silibinin, and silymarin) against AChE and BChE at 1 mg/ml concentration using a microplate-reader assay based on the Ellman method. Among them, only quercetin showed a substantial inhibition (76.2%) against AChE, while genistein (65.7%), luteolin-7-O-rutinoside (54.9%), and silibinin (51.4%) exerted a moderate inhibition on BChE.