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.     

Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of Artichoke leaf extracts in humans

Extracts from artichoke leaves are traditionally used in the treatment of dyspeptic and hepatic disorders. Various potential pharmacodynamic effects have been observed in vitro for mono- and dicaffeoylquinic acids (e.g. chlorogenic acid, cynarin), caffeic acid and flavonoids (e.g. luteolin-7-O-glucoside) which are the main phenolic constituents of artichoke leaf extract (ALE). However, in vivo not only the genuine extract constituents but also their metabolites may contribute to efficacy. Therefore, the evaluation of systemic availability of potential bioactive plant constituents is a major prerequisite for the interpretation of in vitro pharmacological testing. In order to get more detailed information about absorption, metabolism and disposition of ALE, two different extracts were administered to 14 healthy volunteers in a crossover study. Each subject received doses of both extracts. Extract A administered dose: caffeoylquinic acids equivalent to 107.0 mg caffeic acid and luteolin glycosides equivalent to 14.4 mg luteolin. Extract B administered dose: caffeoylquinic acids equivalent to 153.8 mg caffeic acid and luteolin glycosides equivalent to 35.2 mg luteolin. Urine and plasma analysis were performed by a validated HPLC method using 12-channel coulometric array detection. In human plasma or urine none of the genuine target extract constituents could be detected. However, caffeic acid (CA), its methylated derivates ferulic acid (FA) and isoferulic acid (IFA) and the hydrogenation products dihydrocaffeic acid (DHCA) and dihydroferulic acid (DHFA) were identified as metabolites derived from caffeoylquinic acids. Except of DHFA all of these compounds were present as sulfates or glucuronides. Peak plasma concentrations of total CA, FA and IFA were reached within 1 h and declined over 24 h showing almost biphasic profiles. In contrast maximum concentrations for total DHCA and DHFA were observed only after 6-7 h, indicating two different metabolic pathways for caffeoylquinic acids. Luteolin administered as glucoside was recovered from plasma and urine only as sulfate or glucuronide but neither in form of genuine glucosides nor as free luteolin. Peak plasma concentrations were reached rapidly within 0.5 h. The elimination showed a biphasic profile.     

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.     

Neural cell protective compounds isolated from Phoenix hanceana var. formosana

A platform for screening drugs for their ability to protect neuronal cells against cytotoxicity was developed. Nerve growth factor (NGF) differentiates PC12 cells into nerves, and these differentiated PC12 cells enter apoptosis when challenged with 6-hydroxydopamine (6-OHDA). A screening spectrophotometer was used to assay cytotoxicity in these cells; pretreatment with test samples allowed identification of compounds that protected against this neuronal cytotoxicity. The 95% ethanol extract of Phoenix hanceana Naudin var. formosana Beccari. (PH) showed potential neuroprotective activity in these assays. The PH ethanol extract was further fractionated by sequential partitioning with n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH), and water. Subsequent rounds of assaying resulted in the isolation of ten constituents, and their structures were characterized by various spectroscopic techniques and identified by comparison with previous data as: isoorientin (1), isovitexin (2), veronicastroside (3), luteolin-7-O-β-d-glucopyranoside (4), isoquercitrin (5), tricin-7-neohesperidoside (6), tricin-7-O-β-d-gluco-pyranoside (7), (+)-catechin (8), (−)-epicatechin (9), and orientin 7-O-β-d-glucopyranoside (10). Among these compounds, isovitexin (2), luteolin-7-O-β-d-glucopyranoside (4) and (+)-catechin (8) showed significant neuroprotective activity in cell viability (WST-8 reduction), anti-apoptosis (Annexin V-FITC/propidium iodide double-labeled flow cytometry), and cellular ROS scavenging assays (besides isovitexin (2)), as well as a decreased caspase-8 activity in 6-OHDA-induced PC12 cells. Hence, isovitexin (2), luteolin-7-O-β-d-glucopyranoside (4), and (+)-catechin (8) protected PC12 cells from 6-OHDA-induced apoptotic neurotoxicity.     

Molecular mechanisms of luteolin-7-O-glucoside-induced growth inhibition on human liver cancer cells: G2/M cell cycle arrest and caspase-independent apoptotic signaling pathways

Luteolin-7-O-glucoside (LUT7G), a flavone subclass of flavonoids, has been found to increase anti-oxidant and anti-inflammatory activity, as well as cytotoxic effects. However, the mechanism of how LUT7G induces apoptosis and regulates cell cycles remains poorly understood. In this study, we examined the effects of LUT7G on the growth inhibition of tumors, cell cycle arrest, induction of ROS generation, and the involved signaling pathway in human hepatocarcinoma HepG2 cells. The proliferation of HepG2 cells was decreased by LUT7G in a dose-dependent manner. The growth inhibition was due primarily to the G2/M phase arrest and ROS generation. Moreover, the phosphorylation of JNK was increased by LUT7G. These results suggest that the anti-proliferative effect of LUT7G on HepG2 is associated with G2/M phase cell cycle arrest by JNK activation. [BMB Reports 2013; 46(12): 611-616]     

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.     

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.     

Polyphenols from Cornulaca monacantha

The aerial parts of the Egyptian herb Cornulaca monacantha have yielded two new galloyltannin analogs (named monacanthin A and monacanthin B) characterized by protoctechuoyl moiety at C-6, and also a new flavonol glycoside, quercetin-4'-O-beta-D-galactoside. The structures of the new compounds were established by conventional analytical methods and confirmed by spectral analyses. Two known flavonoids, luteolin-7-O-rhamnoside, luteolin-7-O-glucoside, and two known gallotannins, penta-O-galloyl-beta-D-glucose and 1,2,3,6-tetra-O-galloyl-beta-D-glucose were also isolated.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

神农香菊花的化学成分研究(Ⅱ)

对采自湖北神农架的神农香菊（Dendranthema indicum（L）Des Monl．vaY．aromaticum Q．H．LiuetS．F．Zhang var．nov．）的化学成分进行研究,从中分离到5个化合物,利用波谱分析技术和文献对照确定了其结构,分别鉴定为木犀草素（luteolin）,木犀黄酮甙（luteolin-7-O-β-glucopyranoside）,刺槐素甙（acacetin-7-rhamnosidgluoside）,1-单山萮酸甘油酯（glyceryl-1-monobehenate）,山萮酸（behenic acid）。     

Polyphenolic compounds from Plantago lagopus L

In the present study we report the isolation of a phenylpropanoid glucoside, plantamajoside, together with rosmarinic acid, chlorogenic acid and luteolin-7-O-monoglucoside. This is the first report of these compounds from Plantago lagopus.     

Protective effects of luteolin-7-O-β-D-glucuronide methyl ester from the ethyl acetate fraction of Lycopi Herba against pro-oxidant reactive species and low-density lipoprotein peroxidation

In this study the potent scavenging activity of “Lycopi Herba” (LH) extract was studied using the following: evaluation of the total phenolics, measuring the antioxidant activity by Trolox equivalent antioxidant concentration, measuring the scavenging effects on reactive oxygen species, on reactive nitrogen species, and measuring the inhibitory effect on Cu²⁺ induced human low-density lipoprotein oxidation in vitro. The ethyl acetate fraction from the LH extracts were found to have a potent scavenging activity against all of the reactive species tested, as well as an inhibitory effect on LDL oxidation. Therefore, we isolated and identified luteolin-7-O-β-D-glucuronide methyl ester as the major compound from the ethyl acetate fraction of LH and their antioxidant activities were evaluated.     

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。