Effect and mechanism of eriodictyol on non-alcoholic fatty liver disease by regulating MAPK and Nrf2/HO-1 signaling pathway / 中国药房

OBJECTIVE To study the effect and potential mechanism of eriodictyol on non-alcoholic fatty liver disease （NAFLD）. METHODS Sixteen C57BL/6J mice were randomly divided into control group， NAFLD model group， and eriodictyol low-dose and high-dose groups （50， 100 mg/kg）， with 4 mice in each group. Except for control group， the other groups were fed with high fat diet to induce NAFLD model. After four weeks of preprocessing， they were given relevant medicine intraperitoneally （0.01 mL/g）， once a day， for 6 consecutive weeks. The body weight and liver weight of mice were measured， and the pathological damage of liver tissue in mice was observed. The levels of aspartate aminotransferase （AST）， alanine aminotransferase（ALT）， and triglycerides （TG） in serum， as well as the protein expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were determined. In vitro NAFLD model was established by using 0.5 mmol/L oleic acid （OA） in HepG2 cells. Normal control group， NAFLD model group and eriodictyol low-， medium- and high-concentration groups （50， 100， 150 μmol/L） were set up. HepG2 cells in drug groups were treated with eriodictyol for 24 h at the time of modeling. The lipid deposition was observed in cells， and the levels of TG， malondialdehyde （MDA） and reactive oxygen species （ROS） as well as the phosphorylation levels of the mitogen-activated protein kinase （MAPK） signal pathway related proteins [extracellular signal-regulated kinase （ERK）， c- Jun N-terminal kinase （JNK）] and the protein expressions of Nrf2 and HO-1 were all determined. RESULTS In the in vivo experiment， compared with the NAFLD model group， the body weight， liver weight， the serum levels of AST， ALT and TG were all decreased significantly in eriodictyol low- and high-dose groups （except for serum level of AST in eriodictyol low-dose group） （P＜0.01）； liver lipid deposition was reduced significantly and the protein expressions of Nrf2 and HO-1 in liver tissues were further up-regulated （P＜0.01）. In the in vitro experiment， compared with the NAFLD model group， the lipid deposition in hepatocytes was reduced in eriodictyol low-， medium- and high-concentration groups （P＜0.01）， and the levels of ROS， MDA and TG were down-regulated （P＜0.05 or P＜0.01）； the phosphorylation levels of ERK and JNK were significantly down-regulated （P＜0.01）， while the protein expressions of Nrf2 and HO-1 were up-regulated significantly （P＜0.01）. CONCLUSIONS Eriodictyol can inhibit MAPK signaling pathway and activate Nrf2/HO-1 signaling pathway to alleviate NAFLD.

Identification of flavonoids 3-hydroxylase from Silybum marianum (L.) Gaertn and its application in enhanced production of taxifolin / 生物工程学报

(2S)-taxifolin is an important flavonoid that has anti-inflammatory and anti-oxidation effects. It is widely used in pharmaceutical and nutraceutical industries. Flavone 3-hydroxylase (F3H) can catalyze the synthesis of (2S)-taxifolin and other 3-hydroxylated flavonoids from (2S)-eriodictyol. Due to the low catalytic efficiency of F3H, the titer of many 3-hydroxyflavones, such as taxifolin, synthesized by microbial method is relatively low. In this study, a SmF3H was identified from the transcriptome of Silybum marianum (L.) Gaertn. The results of fermentation showed that SmF3H can catalyze the flavone 3-hydroxylation reaction, and its catalytic efficiency was significantly higher than that of commonly used SlF3H from Solanum lycopersicum. Six promoters with different transcription strength were selected to optimize the synthesis pathway from the flavonoid precursor (2S)-naringenin to (2S)-taxifolin. The results showed that the highest titer of (2S)-taxifolin (695.90 mg/L in shake flask) could be obtained when the P(GAL7) promoter was used to control the expression of SmF3H. The titer of (2S)-taxifolin was further improved to 3.54 g/L in a 5-L fermenter, which is the highest titer according to current available literatures.

A new diphenylpropanoid from Cassia floribunda / 中草药

Objective: To study the chemical composition of the stems and leaves of Cassiafloribunda. Methods: The chemical constituents from stems and leaves of C. floribunda were isolated by silica gel MCI, RP-18, TLC, and HPLC methods. Their structures were elucidated by spectroscopic methods and physicochemical properties. Results: Eighteen compounds were isolated from the 90% EtOH extract of C. floribunda and their structures were established ascassia cis-transdiphenylpropanoid(1), ethyl p-hydroxycinnamate (2), shonanin(3), dibutyl phthalate(4), 1,6,8-trihydroxyl-3-methyl-anthraquinone (5), 2,5-dimethyl-7-hydroxyl-chromogen, (6), 2-(2'-hydroxypropyl)-5-methyl-7-hydroxytryptophan(7), 4',7-dihydroxy-5-methoxy flavone(8), chrysoeriol(9), kaempferol(10), apigenin(11), 3-methoxy quercetin(12), 6-demethoxycapillarisin(13), 7,4'-dihydroxyflavone(14), luteolin(15), butin(16), liquiritigenin(17) anderiodictyol(18). Conclusion: Compound 1 is a new compound, and 2-18 are isolated from this plant for the first time.At the moment,2-4, 8, 9, 11, 13, 14, 16-18 are isolated from Cassia for the first time.

Chemical Constituents of Hypericum uralum and the Analgesic and Antimalarial Activities / 中国药学杂志

OBJECTIVE: To study the chemical constituents of Hypericum uralum were isolated and identified and test the analgesic activity and β-hematin formation inhibitory activity of some selected compounds. METHODS: The compounds were isolated and purified by column chromatography padded with the separating material including silica gel and Sephadex LH-20, and their structures were elucidated based on the analyses of modern spectrum technology. Analgesic and antimalarial activities of selected compounds from H. uralum were evaluated by acetic acid-induced writhing, hot water tail-flick test in mice, and β-hematin formation inhibition method, respectively. RESULTS: Thirteen compounds were isolated from ethyl acetate portion of 95% ethanol extract of H. uralum and identified as (-)-eriodictyol (1), 3,4,5-trihydroxyxanthone (2), 1,7-dihydroxyxanthone (3), 4-hydroxy-2,3-dimethoxyxanthone (4), toxyloxanthone B (5), 1,3,6,7-tetrahydroxyxanthone (6), 2,3-dimethoxyxanthone (7), 1,5,6-trihydroxy-3-methoxyxanthone (8), hyperielliptone HD (9), 3,3′,4,4′-tetrahydroxybiphenyl (10), shikimic acid (11), quercetin-3-O-(4″-methoxy)-α-L-rahmnopyranosyl (12), and proanthocyanidin A-2 (13). The analgesic activity test indicated that compounds 3 and 12 had certain peripheral analgesic activity, while compound 1 exhibited strong β-hematin formation inhibitory activity. CONCLUSION: All the compounds are obtained from this plant for the first time.The analgesic and antimalarial activities of H. uralum have corresponding material basis.

Advances in studies on pharmacological effects of eriodictyol / 中草药

Eriodictyol is a natural flavonoid which is abundant in vegetables, fruits and some Chinese medicines with many pharmacological effects such as anti-oxidation, anti-inflammatory, antitumor and neuroprotection. It has been used in the treatment of asthma, allergic rhinitis, rheumatism and other diseases frequently. With the deeper research on eriodictyol, the mechanism of its pharmacological effect has been found to be involved in nuclear factor erythroid-2-related factor 2 (Nrf2), nuclear transcription factor-κB (NF-κB), and protein kinase B (PKB/Akt) signal pathways. In this paper, we summarize the recent research progress on pharmacological effects of eriodictyol, with purpose to offer reference in further research, development and utilization.

Chemical constituents of acrial part of Bupleunum malconense / 中草药

Objective: To investigate the chemical constituents in the dried acrial part of Bupleunum malconense. Methods: Column chromatography, such as silica gel, MCI, and Sephadex LH-20 were used to isolate the compounds. Spectroscopic methods such as 1H-NMR and 13C-NMR were used to elucidate their structures. Results: Eleven compounds were separated and identified as quercetin (1), quercetin-3-O-α-L-arabinofuranoside (2), eriodictyol (3), 3',4',5,7-tetrahydroxy-3-methoxyflavone (4), protocatechuic acid (5), quercetin-3-O-α-L-rhamnopyranoside (6), kaempferol (7), isorhanmetin (8), rutin (9), β-sitosterol (10), and daucosterol (11). Conclusion: All 11 compounds are isolated from the plants in B. malconense for the first time. Compounds 3 and 4 are isolated from the plants in genus Bupleunum L. for the first time.

Chemical constituents from aerial parts of Leonurus macranthus / 中草药

Objective: To investigate the chemical constituents from the aerial parts of Leonurus macranthus. Methods: The chemical constituents were separated and purified by silica gel, Sephadex LH-20, ODS column chromatographies, and semi-preparative HPLC. Their structures were determined by physicochemical properties and spectroscopic data. Results: Nineteen compounds were isolated from the CH2Cl2 layer of 70% aqueous acetone extract in the aerial parts of L. macranthus, and identified as (+)-syringaresinol (1), (+)-1-hydroxysyringaresinol (2), rayalinol (3), erythro-guaiacylglycerol-β-O-4'-coniferyl ether (4), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-3', 4″- dihydroxy-3, 5, 4', 5″-tetramethoxy-7, 9': 7', 9-diepoxy-4, 8″-oxy-8, 8'-sesquineo-lignan-7″, 9″-diol (5), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4', 5″- dihydroxy-3, 5, 3', 4″-tetramethoxy-7, 9': 7', 9-diepoxy-4, 8″-oxy-8, 8'-sesquineo-lignan-7″, 9″-diol (6), genkwanin (7), 3'-hydroxy- genkwanin (8), eriodictyol (9), isoscopoletin (10), p-coumaric acid (11), caffeic acid methyl ester (12), trans-ferulic acid (13), syringic aldehyde (14), vanillic acid (15), oct-1-en-3-yl β-glucopyranoside (16), 5-hydroxy-2-pyrrolidone (17), pterolactam (18), and nicotinamide (19), respectively. Conclusion: Compounds 1-6 and 9-19 are isolated from the plants of genus Leonurus Linn. for the first time, and compounds 7 and 8 are found from L. macranthus for the first time.

Eriodictiol protege camundongos submetidos à isquemia cerebral focal permanente, do danoneuronal, déficit de memória e resposta inflamatória

O Acidente Vascular Encefálico (AVE) é definido como um quadro clínico de déficit neurológico que pode perdurar ou exceder as primeiras vinte e quatro horas do evento. A Organização Mundial de Saúde (OMS) revela que entre os anos de 2000 e 2011, o AVE apresentou-se como a segunda principal causa de óbitos em todo o mundo. Segundo o Ministério da Saúde, o AVE é a principal causa de morte no Brasil. É causado pela diminuição da perfusão sanguínea com depleção de oxigênio e glicose ao cérebro, causando redução dos níveis de ATP e predispondo a eventos como: excitotoxicidade glutamatérgica, influxo exacerbado de Ca++, estresse oxidativo, inflamação e apoptose, resultando em morte neuronal. O eriodictiol (3‟,4‟,5,7-tetrahidroxiflavanona) é um flavonóide encontrado na erva chinesa (Dracocephalum rupestre). Possui atividades anti-inflamatória, antioxidante e antiapoptótica já reportadas. O objetivo deste trabalho foi estudar os efeitos do eriodictiol sobre o dano neuronal, déficits de memória e resposta infamatória de camundongos submetidos à isquemia cerebral focal por oclusão permanente da artéria cerebral média (pMCAO). Os animais foram tratados oralmente com eriodictiol (1, 2 e 4 mg / kg) ou veículo (5% Tween 80 em salina 0,9%) 30 min antes, 2 horas depois da pMCAO e diariamente durante 4 dias. A pMCAO promoveu dano cerebral nos animais isquemiados, sendo esse comprovado, por meio da detecção do aumento significativo nas percentagens das áreas de infarto, pelos déficits sensório-motores observados e pela perda da viabilidade neuronal. O eriodictiol reduziu a área de infarto cerebral nas doses de 1, 2 e 4 mg/kg e preveniu os animais isquemiados dos déficits neurológicos 24h após pMCAO...

Stroke is defined as a clinical neurological deficit that may last or exceed the first twenty-four hours of the event. The World Health Organization (WHO) reveals that between 2000 and 2011, the Stroke was presented as the second leading cause of death worldwide. According to the Ministry of Health, stroke is the leading cause of death in Brazil. It is caused by decreased blood perfusion depleted of oxygen and glucose to the brain,causing ATP reduction levels and predisposing to events such as glutamatergic excitotoxicity, exacerbated influx of Ca++, oxidative stress, inflammation and apoptosis, resulting in neuronal death. The eriodictyol (3 ', 4', 5,7-tetrahydroxyflavanone) is a flavonoid found in the Chinese herb (Dracocephalum rupestre) having anti-inflammatory, antioxidant and anti-apoptotic effects previously reported. The objective of this study was to analyze the effects of eriodictyol on neuronal damage, memory deficits and inflammatory-response of mice subjected to focal cerebral ischemia by permanent meddle cerebral artery occlusion (pMCAO). The animals were treated orally with eriodictyol (1, 2 and 4 mg / kg) or vehicle (5% Tween 80 in saline 0,9%) 30 minutes before, 2 hours after the pMCAO and daily for 4 days. The promoted pMCAOischemic brain damage in animals, this being confirmed by means of detection of a significant increase in the percentage of infarcted areas, the observed sensorimotor deficits and loss of neuronal viability. The eriodictyol reduced the area of cerebral infarction in doses of 1, 2 and 4 mg / kg and prevented the animal-ischemic neurological deficits 24h post-pMCAO...

Phytochemical analysis of Vernonanthura tweedieana and a validated UPLC-PDA method for the quantification of eriodictyol

AbstractVernonanthura tweedieana (Baker) H. Rob., Asteraceae, is used in the Brazilian folk medicine for the treatment of respiratory diseases. In this work the phytochemical investigation of its ethanol extracts as well as the development and validation of an UPLC-PDA method for the quantification of the eriodictyol from the leaves were performed. The phytochemical study for this species lead to the identification of ethyl caffeate, naringenin and chrysoeriol in mixture, eriodictyol from leaves, and the mixture of 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-propan-1-one and evofolin B, apigenin, the mixture of caffeic and protocatechuic acid and luteolin from stems with roots, being reported for the first time for V. tweedieana, except for eriodictyol. The structural elucidation of all isolated compounds was achieved by 1H and 2D NMR spectroscopy, and in comparison with published data. An UPLC-PDA method for quantification of the eriodictyol in leaves of V. tweedieana was developed and validated for specificity, linearity, precision (repeatability and intermediate precision), limit of detection (LOD) and limit of quantification (LOQ), accuracy and robustness. In this study, an excellent linearity was obtained (r2 = 0.9999), good precision (repeatability RSD = 2% and intermediate precision RSD = 8%) and accuracy (average recovery from 98.6% to 99.7%). The content of eriodictyol in the extract of leaves of V. tweedieana was 41.40 ± 0.13 mg/g. Thus, this study allowed the optimization of a simple, fast and validated UPLC-PDA method which can be used to support the quality assessment of this herbal material.

Acetylcholinesterase Inhibitory Activity After in vitro Gastrointestinal Digestion of Infusions of Mentha Species.

Aims: To study the acetylcholinesterase inhibitory activity of Mentha infusions before and after the gastrointestinal digestion and to correlate this activity with the chemical compounds present in these infusions. Place and Duration of Study: Fresh Mentha x piperita, M. spicata, M. pulegium were bought in a local supermarket. These plants were composed of leaves, stems and flowers for the identification, which was carried out in Plant Biotechnology Centre, Faculty of Sciences, University of Lisbon. The chemical identification of the infusions and the enzymatic tests were carried out in the Center of Chemistry & Biochemistry, Faculty of Science University of Lisbon from September 2010 till June 2011. Methodology: The compounds present in the infusions were identified by LC-MS. The enzyme activity assay was carried out using a spectrophotometric method. The digestive simulation was accomplished using enzymatic juices prepared in the laboratory and Caco-2 cells lines simulating the intestine barrier. Results: All the Mentha infusions contained rosmarinic acid. M. spicata infusion contained also eriocitrin and eriodictyol. The IC50 values for acetylcholinesterase inhibitory activity of the infusions, before digestion, stayed between 0.72 and 1.9 mg/mL. These activities are statistically different at p<.05. These activities can be explained by the presence of the phenolic compounds mentioned. Rosmarinic acid has an IC50 equal to 0.439 mg/mL (1.22 mM), eriocitrin and eriodictyol have IC50 equal to 0.439 mg/mL (0.29 mM) and 0.256 mg/mL (0.89 mM) respectively. The presence of these two flavonoids, eriocitrin and eriodictyol, can account for the higher activity detected for M. spicata. The gastric juice or the pancreatic juices used to simulate the gastrointestinal digestion did not originate any difference in the chemical composition of the infusions (analysed by HPLCDAD). This was also corroborated by the enzymatic tests. The Caco-2 cells did not originate any modification in the enzymatic activity of the infusions. The analysis of the cell homogenate revealed the presence of rosmarinic acid and the phenolic compounds, although in minor amount. Conclusion: Mentha infusions have the capacity to inhibit acetylcholinesterase, due to the presence of rosmarinic acid, eriocitrin and eriodictyol The composition of the Mentha herbal teas was not modified by the gastro-intestinal juices, or by the intestinal cell line.

Polyphenols from leaves of Olea europaea / 中草药

Objective: To study the polyphenols from the leaves of Olea europaea. Methods: The polyphenols from ethyl acetate fraction were separated and purified by silica chromatographic method and identified by spectroscopic analysis. Results: In combination with the data from literatures, the structure of 15 polyphenols had been elucidated on the basis of various spectroscopic methods, including tyrosol (1), hydroxytyrosol (2), hydroxytyrosol acetate (3), 1H-2-benzopyran-6,7-diol (4), 3,4-dihydroxyl-benzoic acid (5), 3-methoxyl-4-hydroxyl benzoic acid (6), isorhamnetin (7), eriodictyol (8), taxifolin (9), quercetin (10), luteolin (11), ligstroside (12), oleuropein (13), apigenin-7-O-glucoside (14), and luteolin-7-O-glucoside (15). Conclusion: Compounds 4-9 are isolated from this plant for the first time.

Flavanones from aerial parts of Cordia globosa (Jacq.) Kunth, Boraginaceae / Flavanonas isoladas das partes aéreas de Cordia globosa (Jacq.) Kunth (Boraginaceae)

The phytochemical analysis of aerial parts of Cordia globosa, collected in the Municipality of Picuí, State of Paraíba, Brazil, resulted in the isolation and structural identification of narigenin-4',7-dimethyl ether (0.025 g) and eriodictyol (0.015 g). These compounds are the first flavanones aglycones isolated from the genus Cordia.

A análise fitoquímica das partes aéreas de Cordia globosa, coletadas no município de Picuí, PB, Brasil, resultou no isolamento e identificação estrutural da 7,4'-dimetilnarigenina (0,025 g) e eriodictiol (0,015 g). Estas duas flavanonas são as primeiras agliconas, desta classe, isoladas no gênero Cordia.

Determination of total flavonoids,eriodictyol-7-methylether and isosakuranetin in seeds of Artemisia halodendron Turcz / 中华中医药杂志

Objective:To establish a method for determination of total flavonoids,eriodictyol-7-methylether and isosakuranetin in Artemisia halodendron seeds.Method:The content of total flavonoids was determined by ultraviolet spectrophotometry at 506 nm,and compared with eriodictyol-7-methylether as a reference substance;the content of eriodictyol-7-methylether and isosakuranetin was determined by RP-HPLC,the analytical column was YMC-Pack ODS-A column(5?m,4.6 mm?250 mm),the mobile phase consisted of acetonitrile-0.2% phosphoric acid aqueous(35:65) at a ow rate of 1.0 ml?min-1,and the detection wavelength was 288 nm.Results:The linear range of total avonoids was 0.1228--0.7368mg(r=0.9991) and the average recovery(n=6) was 100.5%(RSD=1.41%);the linear ranges of eriodictyol-7-methylether and isosakuranetin were 3.016--30.16?g/ml(r=0.9999)and 3.304--33.04?g/ml(r=0.9999),respectively;the average recoveries(n=6) were 98.9%(RSD=1.20%)and 96.8%(RSD=1.38%),respectively.Conclusion:The methods of UV and HPLC are simple,accurate with good reproducibility and suitable for determination of total avonoids,eriodictyol-7-methylether and isosakuranetin.