- 1. In vitro permeability analysis, pharmacokinetic and brain distribution study in mice of imperatorin, isoimperatorin and cnidilin in Radix Angelicae Dahuricae.
Coumarins are important constituents of Radix Angelicae Dahuricae, a well-known traditional Chinese medicine possess several known bioactivities with potentials in the treatment of central nervous system diseases. By using an HPLC-MS/MS method, we analyzed the in vivo plasma and brain pharmacokinetics of three ingredients of coumarins, including imperatorin, isoimperatorin and cnidilin in mice after oral administration of Dahuricae extract at doses of 800mg/kg. The biosamples were prepared using acetonitrile precipitation and the separation was achieved on an XDB-C18 column by gradient elution. The BBB permeability and P-gp-mediated efflux were further examined in Madin Canine kidney cells transfected with full length cDNA for human multidrug resistance gene1 (MDCKII-MDR1). Our results demonstrate that the method has excellent and satisfactory selectivity, sensitivity, linearity, precision, and accuracy for simultaneous determination of imperatorin, isoimperatorin and cnidilin. The pharmacokinetics parameters were determined by using noncompartmental analyses, including the AUC(0-t) in plasma (1695.22, 1326.45 and 636.98mg*h/L), the AUC(0-t) in brain (1812.35, 2125.17 and 1145.83ng*h/g) as well as the T1/2 in plasma (0.66, 0.82, 0.97h) and brain (0.96, 1.1, 0.99h) for imperatorin, isoimperatorin and cnidilin, respectively, suggesting that the three coumarins could easily pass through the BBB in vivo. In the in vitro model we observed high permeability of imperatorin and isoimperatorin with the P-gp-mediated efflux ratios of 0.53 and 0.06, as well as medium permeability of cnidilin with 0.82. All data suggest that these three coumarins have high BBB permeability and have pharmacokinetic potentials for the treatment of central nervous system diseases....(more)
Lili W, et al. Fitoterapia 2013 Mar;85:144-53.
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- 2. Simultaneous determination of scopoletin, psoralen, bergapten, xanthotoxin, columbianetin acetate, imperatorin, osthole and isoimperatorin in rat plasma by LC-MS/MS for pharmacokinetic studies following oral administration of Radix Angelicae Pubescentis e
A rapid and sensitive bioassay based on liquid chromatography tandem mass spectrometry (LC-MS/MS) has been developed and validated for the simultaneous determination of eight coumarins in rat plasma. The liquid-liquid extraction method with ethyl acetate was used to prepare the plasma samples after addition of warfarin as an internal standard (IS). Chromatographic separation was performed on an Eclipse plus C18 column (100mm×4.6mm, 1.8μm) using gradient elution when 1mM ammonium acetate aqueous solution - acetonitrile was used as the mobile phase. The lower limit of quantitation (LLOQ) of each coumarin was lower than 2.16ngmL(-1). Intra-day and inter-day precisions were less than 15%. The accuracies were in the range of 88.9-117%. The mean recoveries of coumarins and IS were higher than 84%. The method was successfully applied to a pharmacokinetic study of eight coumarins in rats after oral administration of radix angelicae pubescentis....(more)
Chang YX, et al. J Pharm Biomed Anal 2013 Apr 15;77:71-5.
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- 3. Pharmacokinetics and tissue distribution study of schisandrin B in rats by ultra-fast liquid chromatography with tandem mass spectrometry.
A rapid, sensitive and high throughput ultra-fast liquid chromatography with tandem mass spectrometry (UFLC-MS/MS) method was established and validated for the determination of schisandrin B in rat plasma and various tissues (including heart, liver, spleen, lung, and kidney). The biological samples were prepared by protein precipitation, and the separation was achieved on a shim-pack XR-ODS C18 column (75mm×3.0mm, 2.2μm) with a mobile phase consisting of methanol-0.1% formic acid water (85:15, v/v) at a flow rate of 0.4mL/min. The MS/MS detection was performed on an API 3200 QTRAP mass spectrometry equipped with electrospray ionization (ESI) source using multiple reactions monitoring (MRM) mode by monitoring the fragmentation of m/z 401.2→300.2 for schisandrin B and m/z 271.2→203.1 for imperatorin (internal standard, IS). The calibration curve was linear in the range of 1-500ng/mL for plasma and tissue homogenates (r≥0.9927). The lower limit of quantification (LLOQ) was 1ng/mL. The validated method was successfully applied to the pharmacokinetics and tissue distribution study of schisandrin B after oral administration to rats. The pharmacokinetic curve showed double peaks after oral administration, which demonstrated that a hepatoenteral circulation may exist. Tissue distribution showed the highest level was observed in liver, then in kidney, which indicated schisandrin B was mainly accumulated in liver and renal excretion might be a main elimination route....(more)
Zhu H, et al. J Pharm Biomed Anal 2013 May 5;78-79:136-40.
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- 4. Biotransformation of imperatorin by Penicillium janthinellum. Anti-osteoporosis activities of its metabolites.
Imperatorin (IMP) is a major constituent of many herbal medicines and possesses anti-osteoporosis activity. The present research work aimed to study the biotransformation processes of IMP and evaluated the anti-osteoporosis activity of the transformed metabolites. Among 18 strains of filamentous fungi screened, Penicillium janthinellum AS 3.510 exhibited good capability to metabolise IMP to the new derivatives. Ten transformed products were isolated and purified, and their structures were identified accurately based on spectroscopic data. Eight metabolites (2-8 and 10) were novel and previously unreported. The major biotransformation reactions involved hydroxylation of the prenyloxy side-chain and the lactone ring-opening reaction of furocoumarin skeleton. In addition, anti-osteoporosis activities of all products (1-10) were evaluated using MC3T3-E1 cells. The results showed that products 5 and 8 had the best bioactivities in increasing MC3T3-E1 cell growth. These products could be used in future therapeutic regimens for treating osteoporosis....(more)
Lv X, et al. Food Chem 2013 Jun 15;138(4):2260-6.
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- 5. Quantitative NMR: an applicable method for quantitative analysis of medicinal plant extracts and herbal products.
INTRODUCTION:
Quantitative analysis and standardisation of plant extracts or herbal products is a tedious process requiring time-consuming sample preparation and analytical method development for the resolution of analyte peaks from the complex natural extract. Quantitative analysis by HPLC requires a pure authentic standard of the compound being quantified. We report here a quantitative NMR (qNMR) method for quantitative analysis of three medicinal plant extracts and their herbal products without the need of authentic standards. Quantitation can be done by using any commercially available pure sample as an internal reference standard.
OBJECTIVE:
To develop a reliable method for standardisation and quantitative analysis of extracts from medicinal plants Eugenia jambolana, Withania somnifera and Aegle marmelos and their herbal products using qNMR.
METHODOLOGY:
The (1) H-NMR spectra of known amounts of crude plant extracts with internal standards were recorded in deuterated solvents and quantitation was performed by calculating the relative ratio of the peak area of selected proton signals of the target compounds and the internal reference standard. Anthocyanins [delphinidin-3,5-diglucoside (1), petunidin-3,5-diglucoside (2) and malvidin-3,5-diglucoside (3)] for E. jambolana fruit extract and imperatorin (4) for A. marmelos fruit extract were selected as marker constituents for quantitation and 1,3,5-trimethoxybenzene (TMB) was used as an internal reference standard. Total withanolide content was determined for W. somnifera using 2,4-diformyl phloroglucinol as an internal reference standard.
RESULTS:
The (1) H-NMR gave a linear response for the marker constituents, anthocyanins, withaferin A and imperatorin. Using the described method, the amount of anthocyanins in Amberlite(R) XAD7HP and Sephadex enriched extracts of E. jambolana was 3.77% and 9.57% (delphinidin-3,5-diglucoside), 4.72% and 12.0% (petunidin-3,5-diglucoside), 6.55% and 15.70% (malvidin-3,5-diglucoside), respectively. The imperatorin content was 0.424% in A. marmelos fruit and 0.090 % and 0.114% in sharbat and candies. Total withanolides content was 0.191% in the chloroform extract and 0.234% in the capsule extract. These values are in accordance with HPLC results.
CONCLUSION:
This qNMR technique could be used for NMR fingerprinting and quantitation for the purpose of quality control and standardisation of many plant-based herbal products and medicines and has certain advantages over HPLC.
Copyright © 2012 John Wiley & Sons, Ltd....(more)
Chauthe SK, et al. Phytochem Anal 2012 Nov-Dec;23(6):689-96.
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- 6. [Simultaneous determination of three coumarins in Angelica dahurica var. formosana by QAMS].
OBJECTIVE:
To develop a quantitative analysis of multi-components by single marker(QAMS) method for simultaneous determination of three coumarins in Angelica dahurica var. formosana, by using one standard substance.
METHOD:
With imperatorin as internal reference standard, and 2 relative correction factors (RCF) to imperatorin were calculated within certain ranges. Their contents in 20 batches of samples, collected from different areas, were determined by both external standard method and QAMS. The method was evaluated by comparison of the quantitative results between the two methods.
RESULT:
No significant differences were found in the quantitative results of three coumarins in 20 batches of A. dahurica var. formosana determined by the two methods (RSD < 5%).
CONCLUSION:
QAMS is feasible and suitable for quality control of A. dahurica var. formosana....(more)
Yang F, et al. Zhongguo Zhong Yao Za Zhi 2012 Apr;37(7):956-60. Chinese.
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- 7. Simultaneous determination of imperatorin and its 2 metabolites in dog plasma by using liquid chromatography-tandem mass spectrometry.
In this study, 2 metabolites of imperatorin, imperatorin hydroxylate (IMH) and imperatorin epoxide (IME), were identified for the first time in dog plasma. A sensitive, specific, and accurate high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was then developed for the simultaneous quantification of imperatorin and its 2 metabolites in dog plasma. Separation was achieved on an Agilent ZORBAX Extend-C(18) column (2.1 mm × 50 mm, 3.5 μm) at 30 °C. The mobile phase consisted of 0.02% ammonium acetate solution-methanol with a gradient program at a flow rate of 0.3 mL/min. Detection was performed using an electrospray ionization source operating in positive ion multiple reaction monitoring mode and by monitoring the ion transitions from 271 to 203 m/z for imperatorin, 309.4-224.1 m/z for IMH, 287-203 m/z for IME, and 441.3-325.2 m/z for simvastatin (the internal standard). Good linearity was shown over the concentration range of 1-500 ng/mL for imperatorin, and 0.2-500 ng/mL for IMH and IME. The validated method was successfully applied to a pharmacokinetic study of imperatorin in beagle dogs. The pharmacokinetic profiles of imperatorin and its 2 metabolites showed sex differences after the i.v. administration of imperatorin at a dose of 5 mg/kg....(more)
Wang L, et al. J Pharm Biomed Anal 2012 Nov;70:640-6.
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- 8. Two new tri-nor-eudesmanolides from Inula racemosa.
Two new tri-nor-eudesmane-type sesquiterpenoids were isolated from the roots of Inula racemosa, and their structures were elucidated as 8-oxo-tri-nor-eudesm-6-en-5α-ol (1) and tri-nor-eudesm-5-en-7β,8β-diol (2). The cytotoxic activity of compound 1 against five human cancer cell lines had been tested, but exhibited no cytotoxic activity....(more)
Zhang T, et al. J Asian Nat Prod Res 2013 Apr;15(4):368-72.
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- 9. Structural Investigation and Biological Activity of Sesquiterpene Lactones from the Traditional Chinese Herb Inula racemosa.
Five new sesquiterpene lactones, racemosalactones A-E (1-5), along with 19 known sesquiterpene latones (6-24), were isolated from the roots of Inula racemosa. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 2 was deduced from X-ray diffraction analysis. Compounds 1, 6, 8, 10, 12, 14, and 17 exhibited antiproliferative activities with IC50 values ranging from 0.38 to 4.19 μg/mL against human non-small-cell lung cancer A549, hepatocellular carcinoma HepG2, and human fibrosarcoma HT1080 cells. Compounds 6 and 8 exhibited antiproliferative activities against endothelial cells with IC50 values of 2.4 and 2.5 μg/mL, respectively. Furthermore, compounds 6 and 8 both inhibited endothelial cell tube formation at 1.0 μg/mL. A method for the rapid and straightforward preparative-scale isolation of compound 6 from alantolides is described....(more)
Ma YY, et al. J Nat Prod 2013 Mar 1.
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- 10. Anti-histaminic, mast cell stabilizing and bronchodilator effect of hydroalcoholic extract of polyherbal compound- Bharangyadi.
Bronchial asthma is a chronic inflammatory disorder of the airways associated with reversible airway obstruction and increased airway responsiveness to a variety of stimuli. An intuitive inference from this definition is that a causal relationship may exist between airway inflammation and airway hyperresponsiveness. It can be say that "airway inflammation equal to airway hyperresponsiveness". Attachment of antigen antibody complex to the mast cell causes its disruption and release of inflammatory mediators such as histamine.To evaluate the efficacy of anti-asthmatic property of a drug, evaluation of anti-histaminic, mast cell stabilizing and bronchodilator property can be use as pharmacodynamic parameter. Bharangyadi is a polyherbal compound having Bharangi (Clerodendrum serratum), Sati (Hedychium spicatum) and Pushkarmoola (Inula racemosa) as ingredient herbs The present study aimed to evaluate the anti-asthmatic activity of an indigenous polyherbal compound Bharangyadi through various in-vitro & in-vivo experimental models.The results demonstrate that drug has potent histamine antagonism property with significant mast cell stabilizing and spasmolytic activity in the experimental animals. Compound 48/80, a potent mast cell degranulator, provoked 76% degranulation of mast cells in the control group. Ethanolic extract of Bharangyadi at the doses 500 and 1000 μg/ml protected from compound 48/80-evoked degranulation (P < 0.01) in dose dependent manner.Pre-treatment with Bharangyadi extract showed 80% & 86% protection from histamine induced bronchoconstriction in guinea pigs with 27.8% and 36.1% increase in preconvoulsion time (equal to standard drug). Screening of Histamine antagonism activity on guinea pig ileum showed that drug reduces the smooth muscle contraction in dose dependent manner. Increasing concentration of Bharangyadi extract with maximum dose of histamine (1.6μg) showed maximum inhibition at the dose of 50mg (99.78%). Inhibition of smooth muscle contraction by addition of drug in organ bath before adding histamine showed that drug has preventive type antagonism....(more)
Kajaria D, et al. Anc Sci Life 2012 Jan;31(3):95-100.
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- 11. Sesquiterpenoids from Inula racemosa Hook. f. inhibit nitric oxide production.
A novel trinorsesquiterpene (1), three new (2-4), and 10 known sesquiterpenes were isolated from the roots of Inula racemosa Hook. f. The structures and absolute configurations of the new sesquiterpenes were elucidated by extensive spectroscopic and computational methods. All compounds were evaluated for their inhibition of LPS-induced nitric oxide production in RAW264.7 macrophages, and the results indicated that compounds 9, 12, and 13 moderately inhibited nitric oxide production with IC values of 7.39 ± 0.36, 6.35 ± 0.26, and 5.39 ± 0.18 µM, respectively.
© Georg Thieme Verlag KG Stuttgart · New York....(more)
Zhang SD, et al. Planta Med 2012 Jan;78(2):166-71.
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- 12. A validated Fourier transform infrared spectroscopy method for quantification of total lactones in Inula racemosa and Andrographis paniculata.
INTRODUCTION:
Fourier transform infrared (FT-IR) spectroscopy is a technique widely used for detection and quantification of various chemical moieties. This paper describes the use of the FT-IR spectroscopy technique for the quantification of total lactones present in Inula racemosa and Andrographis paniculata.
OBJECTIVE:
To validate the FT-IR spectroscopy method for quantification of total lactones in I. racemosa and A. paniculata.
METHODOLOGY:
Dried and powdered I. racemosa roots and A. paniculata plant were extracted with ethanol and dried to remove ethanol completely. The ethanol extract was analysed in a KBr pellet by FT-IR spectroscopy. The FT-IR spectroscopy method was validated and compared with a known spectrophotometric method for quantification of lactones in A. paniculata.
RESULTS:
By FT-IR spectroscopy, the amount of total lactones was found to be 2.12 ± 0.47% (n = 3) in I. racemosa and 8.65 ± 0.51% (n = 3) in A. paniculata. The method showed comparable results with a known spectrophotometric method used for quantification of such lactones: 8.42 ± 0.36% (n = 3) in A. paniculata. Limits of detection and quantification for isoallantolactone were 1 µg and 10 µg respectively; for andrographolide they were 1.5 µg and 15 µg respectively. Recoveries were over 98%, with good intra- and interday repeatability: RSD ≤ 2%.
CONCLUSION:
The FT-IR spectroscopy method proved linear, accurate, precise and specific, with low limits of detection and quantification, for estimation of total lactones, and is less tedious than the UV spectrophotometric method for the compounds tested. This validated FT-IR spectroscopy method is readily applicable for the quality control of I. racemosa and A. paniculata.
Copyright © 2011 John Wiley & Sons, Ltd....(more)
Shivali G, et al. Phytochem Anal 2012 Mar-Apr;23(2):171-6.
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- 13. Sesquiterpenoids from Inula racemosa.
Phytochemical research on the roots of Inula racemosa yielded nine sesquiterpenoids including a new nor-eudesmane-type sesquiterpenoid, 11,12,13-trinoreudesm-5-en-7β,8α-diol (1). The structures of isolated compounds were elucidated by extensive spectroscopic methods including 1D and 2D NMR. The structure of compound 2 was confirmed by single-crystal X-ray diffraction analysis....(more)
Xu LW, et al. J Asian Nat Prod Res 2011 Jun;13(6):570-4.
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- 14. Effect of Inula racemosa root extract on cardiac function and oxidative stress against isoproterenol-induced myocardial infarction.
The cardioprotective potential of Inula racemosa root hydroalcoholic extract against isoproterenol-induced myocardial infarction was investigated in rats. The rats treated with isoproterenol (85 mg/kg, s.c.) exhibited myocardial infarction, as evidenced by significant (P < 0.05) decrease in mean arterial pressure, heart rate, contractility, relaxation along with increased left ventricular end diastolic pressure, as well as decreased endogenous myocardial enzymatic and non-enzymatic antioxidants. Isoproterenol also significantly (P < 0.05) induced lipid peroxidation and increased leakage of myocyte injury marker enzymes. Pretreatment with I. racemosa extract (50, 100 or 200 mg/kg per day, p.o.) for 21 consecutive days, followed by isoproterenol injections on days 19th and 20th significantly (P < 0.05) improved cardiac function by increasing the heart rate, mean arterial pressure, contractility and relaxation along with decreasing left ventricular end diastolic pressure. Pretreatment with I. racemosa also significantly (P < 0.05) restored the reduced form of glutathione and endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase from the heart, which were depleted after isoproterenol administration. In addition to restoration of antioxidants, I. racemosa significantly (P < 0.05) inhibited lipid peroxidation and prevented the leakage of myocytes specific marker enzymes creatine phosphokinase-MB and lactate dehydrogenase from the heart. Thus, it is concluded that I. racemosa protects heart from isoproterenol-induced myocardial injury by reducing oxidative stress and modulating hemodynamic and ventricular functions of the heart. Present study findings demonstrate the cardioprotective effect of I. racemosa and support the pharmacological relevance of its use and cardioprotection mechanism in ischemic heart disease as well as substantiate its traditional claim....(more)
Ojha S, et al. Indian J Biochem Biophys 2011 Feb;48(1):22-8.
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- 15. Cardioprotection by Inula racemosa Hook in experimental model of myocardial ischemic reperfusion injury.
To evaluate the cardioprotective potential of Inula racemosa in myocardial ischemic-reperfusion injury, Wistar male albino rats were randomly divided into four groups. The group I and II animals were administered saline orally {(sham, ischemia- reperfusion (I-R) control group)} and animals of group III and group IV received I. racemosa extract (100 mg/kg) for 30 days. On the 30th day, animals of I-R control and I. racemosa treated groups were underwent 45 min of ligation of left anterior descending coronary artery and were thereafter re-perfused for 60 min. In the I-R control group, a significant decrease of mean arterial pressure (MAP), heart rate (HR), contractility, (+)LVdP/dt and relaxation, (-)LVdP/dt and an increase of left ventricular end diastolic pressure (LVEDP) were observed. Subsequent to haemodynamic impairment and left ventricular contractile dysfunction, a significant decline was observed in endogenous myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). Increased lipid peroxidation characterized by malonaldialdehyde (MDA) formation along with depletion of cardiomyocytes specific enzymes, creatine phosphokinase-MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH) in I-R control group compared to sham group revealed I-R injury of heart. However, treatment with I. racemosa significantly restored the myocardial antioxidant status evidenced by increased SOD, CAT, GPx and GSH and prevented leakage of cardio-specific enzymes; CK-MB and LDH and favorably modulated the altered MAP, HR, (+)LVdP/dt, (-)LVdP/dt and LVEDP as compared to I-R control. Furthermore, I-R induced lipid peroxidation was significantly inhibited by I. racemosa treatment. These beneficial cardioprotective effects translated into significant improvement in cardiac function. In conclusion, our study has demonstrated that the cardioprotective effect of I. racemosa likely resulted to improved antioxidant status, haemodynamic and left ventricular contractile function subsequent to suppression of oxidative stress....(more)
Ojha S, et al. Indian J Exp Biol 2010 Sep;48(9):918-24.
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- 16. Two new eudesmanolides from Inula racemosa.
Two new eudesmane-type sesquiterpene lactones were isolated from the roots of Inula racemosa and their structures were elucidated as 3β-hydroxy-11α,13-dihydroalantolactone (1) and 11α-hydroxy-eudesm-5-en-8β,12-olide (2). Their cytotoxic activities against five human cancer cell lines had been tested and compound 2 exhibited weak cytotoxic activity against BEL-7402 and HCT-8 cell lines. The anti-inflammatory activities were also tested, but neither of them showed any activities....(more)
Zhang T, et al. J Asian Nat Prod Res 2010 Sep;12(9):788-92.
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- 17. Activation of caspases and poly (ADP-ribose) polymerase cleavage to induce apoptosis in leukemia HL-60 cells by Inula racemosa.
Inula racemosa Hook.f. commonly known as Pushkarmula (Compositae) has been used as a traditional drug in India, China and Europe. In the present study, 95% ethanolic extract of roots and its fractions (n-hexane, chloroform, n-butanol and aqueous) were evaluated for in vitro cytotoxicity against cancer cell lines of colon, ovary, prostate, lung, CNS and leukemia. The n-hexane fraction containing alantolactone and isoalantolactone as its major constituents was further studied for its mode of action in HL-60 cells. The lowest IC(50) value of n-hexane fraction was 10.25 microg/ml for Colo-205, a colon cancer cell line whereas, 17.86 microg/ml was the highest IC(50) value observed against CNS cancer cell line SF-295. Further studies on HL-60 cells treated with n-hexane fraction at 10, 25 and 50 microg/ml for 6h, revealed that it induces apoptosis through intrinsic as well as extrinsic pathways by generating reactive oxygen species (ROS) intermediates. Mitochondrial dysfunction prompted the release of cytochrome c, translocation of pro-apoptotic protein (Bax), activation of caspase cascade, resulting in the cleavage of some specific substrates for caspase-3 such as poly (ADP-ribose) polymerase (PARP), which eventually leads to apoptosis. The results of present study strongly support further research and development of bioactive constituents from Inula racemosa as potential anticancer agent with possible therapeutic implication.
Copyright 2010 Elsevier Ltd. All rights reserved....(more)
Pal HC, et al. Toxicol In Vitro 2010 Sep;24(6):1599-609.
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- 18. Coumarins from Angelica archangelica Linn. and their effects on anxiety-like behavior.
TRADITIONAL RELEVANCE:
Angelica archangelica Linn. (Apiaceae) is an herb distributed in tropical and subtropical regions of the world. Both in Chinese and Indian system of medicine, it is used for nervous disorders including anxiety, anorexia, migraine and other cerebral diseases.
AIM OF STUDY:
To evaluate the anxiolytic potential of non polar coumarins isolated from A. archangelica Linn.
METHODS AND RESULTS:
A. archangelica Linn. (1 kg) was subjected to extraction in a soxhlet apparatus with petroleum ether (40-60 °C), yield 6.9% w/w. The extract of petroleum ether produced a yellow colored precipitate (YP) which was evaluated for anxiolytic like effect using EPM test and was found significant (**P<0.01) in doses of 5 and 10 mg/kg, po. The precipitate was shown to be a mixture of seven constituents in HPTLC and six on the TLC plate which were further subjected to separation by preparative TLC. Non polar coumarins were isolated namely imperatorin (IM) and isoimperatorin (IIM). YP, IM, IIM were tested for anxiolytic like effects in a dose of 5mg/kg, po along with DZ (1mg/kg, po) using EPM, Light & dark arena and hole board models in rats. All the test drugs were found to have significant (*P<0.05, **P<0.01) activity. IM and IIM have the potential to reduce anxiety but yellow precipitate showed the most promising activity as compared to isolated coumarins. This effect may be due to the synergistic action of all compounds present in the YP or by multiple mechanism of action. The test drugs may have the potential for different receptors.
CONCLUSION:
The mixture of coumarins isolated from A. archangelica and its constituents imperatorin and isoimperatorin have the potential to reduce anxiety but it is the mixture which have more significant activity as compared to its individual components.
Copyright © 2012 Elsevier Inc. All rights reserved....(more)
Kumar D, et al. Prog Neuropsychopharmacol Biol Psychiatry 2013 Jan 10;40:180-6.
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- 19. Determination of cnidilin and its two metabolites in rat plasma by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
Simple, fast, and sensitive HPLC coupled with an electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the simultaneous determination of cnidilin and its two metabolites, 3",8-methoxy-isoimperatorin (M1) and 5"-hydroxyl-8-methoxy-isoimperatorin (M2), in rat plasma has been developed. Pimpinellin was used as the internal standard and the total analysis time was 7 min. Methanol was the only reagent during the process of sample handling used as a protein precipitant. The analytes were separated on a reversed-phase C18 column with gradient elution consisting of 0.5% aqueous formic acid and methanol (containing 0.5% formic acid) in the multiple-reaction monitoring mode. Cnidilin, M1, M2, and the internal standard could be well ionized under positive electrospray ionization conditions. Full validation of the method (linearity, precision, accuracy, limit of detection, and limit of quantification) was carried out and the method was successfully employed in a metabolism study of cnidilin administered to rats at a dose of 24 mg/kg. The pharmacokinetic parameters of cnidilin determined after orally administrating the single coumarin to the rat were obtained and the mass fragmentation pathways for analysis are proposed in this article....(more)
Zhu H, et al. Planta Med 2013 Jan;79(1):30-6.
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- 20. In vitro permeability analysis, pharmacokinetic and brain distribution study in mice of imperatorin, isoimperatorin and cnidilin in Radix Angelicae Dahuricae.
Coumarins are important constituents of Radix Angelicae Dahuricae, a well-known traditional Chinese medicine possess several known bioactivities with potentials in the treatment of central nervous system diseases. By using an HPLC-MS/MS method, we analyzed the in vivo plasma and brain pharmacokinetics of three ingredients of coumarins, including imperatorin, isoimperatorin and cnidilin in mice after oral administration of Dahuricae extract at doses of 800mg/kg. The biosamples were prepared using acetonitrile precipitation and the separation was achieved on an XDB-C18 column by gradient elution. The BBB permeability and P-gp-mediated efflux were further examined in Madin Canine kidney cells transfected with full length cDNA for human multidrug resistance gene1 (MDCKII-MDR1). Our results demonstrate that the method has excellent and satisfactory selectivity, sensitivity, linearity, precision, and accuracy for simultaneous determination of imperatorin, isoimperatorin and cnidilin. The pharmacokinetics parameters were determined by using noncompartmental analyses, including the AUC(0-t) in plasma (1695.22, 1326.45 and 636.98mg*h/L), the AUC(0-t) in brain (1812.35, 2125.17 and 1145.83ng*h/g) as well as the T1/2 in plasma (0.66, 0.82, 0.97h) and brain (0.96, 1.1, 0.99h) for imperatorin, isoimperatorin and cnidilin, respectively, suggesting that the three coumarins could easily pass through the BBB in vivo. In the in vitro model we observed high permeability of imperatorin and isoimperatorin with the P-gp-mediated efflux ratios of 0.53 and 0.06, as well as medium permeability of cnidilin with 0.82. All data suggest that these three coumarins have high BBB permeability and have pharmacokinetic potentials for the treatment of central nervous system diseases....(more)
Lili W, et al. Fitoterapia 2013 Mar;85:144-53.
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- 21. Simultaneous determination of scopoletin, psoralen, bergapten, xanthotoxin, columbianetin acetate, imperatorin, osthole and isoimperatorin in rat plasma by LC-MS/MS for pharmacokinetic studies following oral administration of Radix Angelicae Pubescentis e
A rapid and sensitive bioassay based on liquid chromatography tandem mass spectrometry (LC-MS/MS) has been developed and validated for the simultaneous determination of eight coumarins in rat plasma. The liquid-liquid extraction method with ethyl acetate was used to prepare the plasma samples after addition of warfarin as an internal standard (IS). Chromatographic separation was performed on an Eclipse plus C18 column (100mm×4.6mm, 1.8μm) using gradient elution when 1mM ammonium acetate aqueous solution - acetonitrile was used as the mobile phase. The lower limit of quantitation (LLOQ) of each coumarin was lower than 2.16ngmL(-1). Intra-day and inter-day precisions were less than 15%. The accuracies were in the range of 88.9-117%. The mean recoveries of coumarins and IS were higher than 84%. The method was successfully applied to a pharmacokinetic study of eight coumarins in rats after oral administration of radix angelicae pubescentis....(more)
Chang YX, et al. J Pharm Biomed Anal 2013 Apr 15;77:71-5.
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- 22. Study on pharmacokinetics and tissue distribution of pteryxin in mice by ultra-pressure liquid chromatography with tandem mass spectrometry.
Pteryxin is a coumarin compound naturally occurring in the roots of Radix Peucedani, a commonly used as traditional Chinese medicine for the treatment of certain respiratory diseases and hypertension. An UPLC-MS/MS method was established to quantify pteryxin in mouse plasma and tissue homogenates. Isoimperatorin was used as internal standard (IS). The method was based on protein precipitation with methanol for sample preparation. Pteryxin and IS were separated using a UPLC™ BEH C column and eluted with a mobile phase consisting of methanol and water (70:30, v/v) at a flow-rate of 0.2 mL/min. MS/MS detection was carried out by monitoring the fragmentation of m/z 409.3-287.2 for pteryxin and m/z 271.3-185.2 for IS on a triple-quadrupole mass spectrometer. The total run time was only 6 min. The results showed that it had good linearity over a wide concentration range (r > 0.999), and pteryxin was rapidly distributed and then eliminated from mouse plasma (t(½) =1.463 h). The major distribution tissues of pteryxin in mice were liver, and pteryxin was enabled to cross the blood-brain barrier owing to its low polarity. There was no long-term accumulation of pteryxin in mouse tissues....(more)
Wang J, et al. Biomed Chromatogr 2012 Jul;26(7):802-7.
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- 23. Furocoumarins affect hepatic cytochrome P450 and renal organic ion transporters in mice.
Furocoumarins are a group of natural products with many biological activities. Clinical evidences have demonstrated the important contribution of furocoumarins to the toxicity of some foods and herbs. In order to assess liver and kidney toxicity of furocoumarins, male mice were orally administrated with psoralen, isopsoralen, imperatorin, isoimperatorin and xanthotoxin at 20 and 40 mg/kg once daily for 28 days, respectively. No changes of food or water intake were observed in furocoumarins-treated mice. Only 40 mg/kg isopsoralen reduced body weight. 40 mg/kg furocoumarins altered serum activities of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and/or levels of albumin, showing hepatotoxicity. Furthermore, furocoumarins increased activity and protein expression of hepatic microsomal cytochrome P450 (CYP450) 3A11. CYP 2E1 activity and protein expression were suppressed by psoralen and isopsoralen and increased by xanthotoxin. Renal protein levels of organic cation/carnitine transporters (OCT1, OCT2 and OCTN2) and organic anion transporter 3 were increased by most furocoumarins. Renal urate transporter 1, glucose transporter 9 and multidrug resistance protein 4 were influenced by furocoumarins. These findings suggest that furocoumarins may interfere in metabolism, excretion and bioavailability of endogenous and exogenous compounds to impair liver and kidney functions mediated by affecting hepatic CYP450 and renal organic ion transport system....(more)
Wang X, et al. Toxicol Lett 2012 Feb 25;209(1):67-77.
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- 24. Larvicidal activity of Cnidium monnieri fruit coumarins and structurally related compounds against insecticide-susceptible and insecticide-resistant Culex pipiens pallens and Aedes aegypti.
BACKGROUND:
An assessment was made of the toxicity of imperatorin and osthole identified in Cnidium monnieri fruit, 11 related compounds and five insecticides to larvae from insecticide-susceptible Culex pipiens pallens (KS-CP strain) and Aedes aegypti and wild C.p. pallens (YS-CP colony) using a direct-contact mortality bioassay. Results were compared with those of the conventional larvicide temephos.
RESULTS:
Imperatorin (LC(50) = 3.14 and 2.88 mg L(-1) ) was 1.9-, 3.7- and 4.2-fold and 2.4-, 4.5- and 4.6-fold more toxic than isopimpinellin, isoimperatorin and osthole against susceptible C. p. pallens and A. aegypti larvae respectively. Overall, all of the compounds were less toxic than temephos (0.011 and 0.019 mg L(-1) ). The toxicity of these compounds was virtually identical against larvae from the two Culex strains, even though YS-CP larvae were resistant to fenthion (resistance ratio RR = 390), deltamethrin (RR = 164), cyfluthrin (RR = 14) and temephos (RR = 14). This finding indicates that the coumarins and the insecticides do not share a common mode of action. The structure-activity relationship indicates that the chemical structure and alkoxy substitution and length of the alkoxyl side chain at the C8 position are essential for imparting toxicity.
CONCLUSION:
The C. monnieri fruit-derived coumarins and the related coumarins described merit further study as potential insecticides or lead molecules for the control of insecticide-resistant mosquito populations.
Copyright © 2012 Society of Chemical Industry....(more)
Wang Z, et al. Pest Manag Sci 2012 Jul;68(7):1041-7.
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- 25. Pressurized liquid extraction of coumarins from fruits of Heracleum leskowii with application of solvents with different polarity under increasing temperature.
Coumarins are nowadays an important group of organic compounds from natural sources that are useful in a number of fields. Because they possess different pharmacological properties, finding the proper extraction conditions for their separation from plant matrices is a very important step. In this report Pressurized Liquid Extraction (PLE) under different temperature conditions and with different types of extraction solvents were tested. As a matrix, fruits of Heracleum leskowii have been used. A simple reverse phase high-performance liquid chromatographic method (RP-HPLC) coupled with a photodiode array detector (DAD) has been developed for separation and quantitative analysis of the main coumarins. Umbelliferone, xanthotoxin, angelicin, isopimpinellin, bergapten, imperatorin and isoimperatorin were investigated. Bergapten and imperatorin were dominant in almost all extracts in the range of 9.92 ± 0.02-20.93 ± 0.06 and 12.19 ± 0.98-19.07 ± 0.03 mg/100 g, respectively. Dichloromethane and methanol were chosen as the most proper suitable solvents for extraction of coumarins. By increasing the temperature the amount of extracted coumarins increases in petroleum ether and dichloromethane extracts....(more)
Skalicka-Wo?niak K, et al. Molecules 2012 Apr 5;17(4):4133-41.
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- 26. Geographical variation of the furanocoumarin composition of the fruits of Icelandic Angelica archangelica.
Angelica archangelica fruits were collected from 64 locations around Iceland and analysed for furanocoumarins by high-performance liquid chromatography. The average furanocoumarin content was found to be 22.5 mg/g, ranging from 14.0 to 31.6 mg/g. Whereas imperatorin was the main compound in all samples, the order of other compounds was highly diverse. Considerable differences were observed between individuals from the same location and between neighbouring locations. However, strong geographical impact was observed on the composition, with isoimperatorin and bergapten being more pronounced in South Iceland, and oxypeucedanin and an unidentified compound being more pronounced in North Iceland and absent in many samples from South Iceland....(more)
Sigurdsson S, et al. Z Naturforsch C 2012 Jan-Feb;67(1-2):1-7.
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- 27. Simultaneous analysis of six major compounds in Osterici Radix and Notopterygii Rhizoma et Radix by HPLC and discrimination of their origins from chemical fingerprint analysis.
Osterici Radix, the dried roots of Ostericum koreanum Maximowicz, has long been used to treat cold, headache and arthralgia in Chinese medicine. Notopterygii Rhizoma et Radix, the dried rhizomes and roots of Notopterygium incisum Ting et H.T. Chang or Notopterygium forbesii Boiss (family: Umbelliferae), are well-known traditional Chinese medicines. These all herbal medicines were named kangwhoal in China, Japan and Korea. However no discrimination methods for the origin and no simultaneous analysis methods for bioactive components are currently available. We developed simultaneous analysis of six biomarkers including nodakenin (1), oxypeucedanin (2), bisabolangelone (3), notopterol (4), imperatorin (5), and isoimperatorin (6) using HPLC method. HPLC chromatographic separation was conducted with C18 column and mobile phase of acetonitrile (A) - water (B) (gradient, (A) 35%-65% (30 min)). The analytical condition was validated with specificity, selectivity, linearity (correlation coefficients of all bio marker were more than 0.999.), recovery (94.9-106.8%), precision and accuracy (intra and inter RSD < 2.99%). In addition, principal component analysis and cluster analysis was performed on analytical data of 38 commercial kangwhoal samples from different places. We confirmed to classify kangwhoal origins and this study was applied to quality evaluation and chemotaxonomy of medicinal herbs....(more)
Kim S, et al. Arch Pharm Res 2012 Mar;35(4):691-9.
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- 28. Polyphenolics composition of the leaves of Zanthoxylum bungeanum Maxim. grown in Hebei, China, and their radical scavenging activities.
High performance liquid chromatography coupled with tandem mass spectrometry with electrospray ionization and negative ion detection (HPLC-ESI-MS/MS) was used to identify the polyphenols from the leaves of a traditional vegetable and spice, Zanthoxylum bungeanum Maxim., in China by comparison of the retention times and mass spectral fragment with standard substances or related literature. A phenolic acid glucoside, two acids, and eight flavonoids were determined including vanillic acid-4-glucoside (22.75 μg/g, dry weight of leaves), quinic acid (58.58 μg/g), chlorogenic acid (2515.96 μg/g), epicatechin (77.80 μg/g), 5-feruloyquinic acid (16.63 μg/g), syringetin-3-glucoside (103.23 μg/g), rutin (89.41 μg/g), hyperoside (886.36 μg/g), quercetin-3-arabinoside (118.75 μg/g), quercitrin (645.82 μg/g), and isorhamnetin-3-glucoside (104.27 μg/g). The obtained polyphenols show good radical scavenging activities in DPPH and superoxide anion. Through the intracellular antioxidation assay, the result shows that the polyphenols could reduce the ROS in HT-29 cells without cell toxicity....(more)
Yang LC, et al. J Agric Food Chem 2013 Feb 27;61(8):1772-8.
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- 29. Anticoagulant activities of persicarin and isorhamnetin.
Persicarin and isorhamnetin were isolated from Oenanthe javanica and their anticoagulant activities were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). In addition, the effects of persicarin and isorhamnetin on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). The data obtained showed that persicarin and isorhamnetin both prolonged aPTT and PT significantly and inhibited the activities of thrombin and FXa. In addition, they both inhibited the generations of thrombin and FXa in HUVECs. In accordance with these anticoagulant activities, persicarin and isorhamnetin prolonged in vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by persicarin. Interestingly, the anticoagulant and profibrinolytic effects of persicarin were greater than those of isorhamnetin, which suggest that the sulfonate group of persicarin positively regulates its anticoagulatory function. Accordingly, our results suggest that persicarin and isorhamnetin possess antithrombotic activities and that they could provide bases for the development of new anticoagulant agents....(more)
Ku SK, et al. Vascul Pharmacol 2013 Apr;58(4):272-9.
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- 30. Bioavailability of quercetin from its aglycone and its glucorhamnoside rutin in lactating dairy cows after intraduodenal administration.
Because of their health-promoting properties, flavonoids are used in feed supplements for ruminants, although scientific evidence for their efficacy in vivo is limited. It has been shown recently that bioavailability of quercetin is low after ruminal administration in cows because of degradation by the ruminal microbiota. It is unknown whether quercetin could be absorbed from the small intestine in ruminants if degradation is prevented; therefore, we investigated the bioavailability of quercetin after duodenal administration in 6 German Holstein cows. On 88 ± 3 d in milk, each cow received equivalent doses of quercetin [9, 18, or 27 mg of quercetin equivalents (QE)/kg of body weight] either as quercetin aglycone (QA) or as its glucorhamnoside rutin (RU). In addition, 2 control studies with duodenal administration of NaCl solution (0.9%) were conducted per cow to examine concentrations of flavonoids in plasma during regular feeding. Blood samples were collected at defined time intervals over a period of 24h before and after administration of the test compounds. A washout period of 2d was applied between the runs to avoid possible carryover effects. Concentrations of plasma quercetin aglycone and its metabolites isorhamnetin, tamarixetin, and kaempferol were measured after treatment with glucuronidase/sulfatase by HPLC with fluorescence detection. After administration of RU, levels of plasma quercetin did not increase above baseline, irrespective of dose administered. After duodenal administration of QA, the plasma concentration of QA and its methylated metabolites clearly increased above baseline. The maximal plasma concentrations of total flavonols (about 2h after application) increased in a dose-dependent manner but showed high interindividual variability (range 368.8 to 983.3 nmol/L at 27 mg of QE/kg of body weight) but peak time did not differ. Preadministration baseline values of total flavonols were reached again 3 to 4h after QA administration. The bioavailability of quercetin and its metabolites, as measured by the area under the concentration-time curve, was affected by the quercetin source applied, whereby quercetin from RU was unavailable. Taken together, duodenal administration enhanced bioavailability of QA almost to values previously reported in pigs after oral administration of QA. In contrast to findings in monogastrics or after oral administration in cows, quercetin from RU seems to be unavailable when administered duodenally....(more)
Gohlke A, et al. J Dairy Sci 2013 Apr;96(4):2303-13.
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- 31. Evolution of flavonoids in Mouratón berries taken from both bunch halves.
Galicia (N.W. Spain) is a Spanish region with several old-traditional winegrowing areas. There are autochthonous grapevine varieties, such as Vitis vinifera L. cv. Mouratón, considered a biodiversity resource in viticulture and an opportunity for Galician sustainable wine production. Therefore, it is necessary to assess the potential of traditional cultivars to produce quality red wines. In this work, anthocyanin and flavonol evolution was followed in red berries from V. vinifera L. cv. Mouratón. The novelty of this study is that grapes were separately collected from two different positions (tips and shoulders) within the cluster, over ripening to examine the effects of berry position within the fruit cluster on the flavonoid compounds. Derivatives of five anthocyanins (malvidin, peonidin, petunidin, delphinidin and cyanidin) and derivatives of six flavonols (quercetin, myricetin, kaempherol, laricitrin isorhamnetin and syringetin) were detected in both positions within the cluster. Dynamic of anthocyanins (from 819 mg/kg to 1206 mg/kg in tips; and from 786 mg/kg to 1077 mg/kg in shoulders) and dynamic of flavonols (from 25mg/kg to 41 mg/kg in tips; and from 18 mg/kg to 21 mg/kg in shoulders) confirmed their upward trends over ripening. Grapes located inside the shoulder bunch receive less sunlight radiation than those located inside the tip bunch and this fact could explain the different accumulation observed for both positions. These results can be useful for winemakers in order to obtain different final red wine quality....(more)
Figueiredo-González M, et al. Food Chem 2013 Jun 1;138(2-3):1868-77.
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- 32. Antimicrobial activity of Calotropis procera Ait. (Asclepiadaceae) and isolation of four flavonoid glycosides as the active constituents.
Antimicrobial activity of solvent extracts and flavonoids of Calotropis procera growing wild in Saudi Arabia was evaluated using the agar well-diffusion method. A bioassay-guided fractionation of the crude flavonoid fraction (Cf(3)) of MeOH extract which showed the highest antimicrobial activity led to the isolation of four flavonoid glycosides as the bioactive constituents. Structure of compounds have been elucidated using physical and spectroscopic methods including (UV, IR, (1)H, (13)C-NMR, DEPT, 2D (1)H-(1)H COSY, HSQC, HMBC and NOESY). Compounds were found to be the 3-O-rutinosides of quercetin, kaempferol and isorhamnetin, besides the flavonoid 5-hydroxy-3,7-dimethoxyflavone-4'-O-β-glucopyranoside. Most of the isolated extracts showed antimicrobial activity against the test microorganisms, where the crude flavonoid fraction was the most active, diameter of inhibition zones ranged between 15.5 and 28.5 mm against the tested bacterial strains, while reached 30 mm against the fungal Candida albicans. The minimal inhibitory concentrations varied from 0.04 to 0.32 mg/ml against all of the tested microorganisms in case of the crude flavonoid fraction. Quercetin-3-O-rutinoside showed superior activity over the remainder flavonoids. The Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) were more susceptible than the Gram-negative (Pseudomonas aeruginosa and Salmonella enteritidis) and the yeast species were more susceptible than the filamentous fungi. The study recommend the use of such natural products as antimicrobial biorationals....(more)
Nenaah G. World J Microbiol Biotechnol 2013 Feb 17.
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- 33. Potent α-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris.
As a part of our ongoing effort to identify anti-diabetic constituents from natural sources, we examined the inhibitory activity of the methanol extracts of 12 species of the genus Artemisia, against α-glucosidase and protein tyrosine phosphatase 1B (PTP1B). The methanol extracts of different species exhibited promising α-glucosidase and PTP1B inhibitory activities. Since the methanol extract of Artemisia capillaris exhibited the highest α-glucosidase inhibitory activity together with significant PTP1B inhibitory activity, it was selected for further investigation. Repeated column chromatography based on bioactivity guided fractionation yielded 10 coumarins (esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7-methoxy coumarin, scoparone, scopoletin, 6-methoxy artemicapin C), 8 flavonoids (hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3-robinobioside, linarin, isorhamnetin 3-glucoiside), 6 phenolic compounds (1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid methyl ester, 4,5-dicaffeoylquinic acid, 3-caffeoylquinic acid), and one chromone (capillarisin). Among these compounds, esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3,5-dicaffeoylquinic acid methyl ester, 3,4-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid exhibited potent α-glucosidase inhibitory activity when compared to the positive control acarbose. In addition, esculetin and 6-methoxy artemicapin C displayed PTP1B inhibitory activity. Interestingly, all isolated dicaffeoylquinic acids showed significant PTP1B inhibitory activity. Therefore, the results of the present study clearly demonstrate the potential of the A. capillaris extract to inhibit α-glucosidase and PTP1B. These inhibitory properties can be largely attributed to a combination of different chemical structures, including coumarins, flavonoids, and dicaffeoylquinic acids, which could be further explored to develop therapeutic or preventive agents for the treatment of diabetes....(more)
Nurul Islam M, et al. Arch Pharm Res 2013 Feb 24.
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- 34. Isorhamnetin inhibits Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages via anti-inflammatory heme oxygenase-1 induction and inhibition of nuclear factor-&amp;kgr;B and signal transducer and activat
BACKGROUND AND OBJECTIVE:
Interleukin-6 (IL-6) is a key proinflammatory cytokine that has been considered to be important in the pathogenesis of periodontal disease. Therefore, host-modulatory agents directed at inhibiting IL-6 appear to be beneficial in terms of attenuating periodontal disease progression and potentially improving disease susceptibility. In the current study, we investigated the effect of the flavonoid isorhamnetin on the production of IL-6 in murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action.
MATERIAL AND METHODS:
Lipopolysaccharide from P. intermedia ATCC 25611 was isolated using the standard hot phenol-water method. Culture supernatants were collected and assayed for IL-6. We used real-time PCR to quantify IL-6 and heme oxygenase-1 (HO-1) mRNA expression. The expression of HO-1 protein and the levels of signaling proteins were monitored using immunoblot analyses. The DNA-binding activity of nuclear factor-κB (NF-κB) was analyzed using ELISA-based assay kits.
RESULTS:
Isorhamnetin significantly down-regulated P. intermedia LPS-induced production of IL-6 as well as its mRNA expression in RAW264.7 cells. Isorhamnetin up-regulated the expression of HO-1 at both gene transcription and translation levels in cells stimulated with P. intermedia LPS. In addition, inhibition of HO-1 activity by tin protoporphyrin IX blocked the inhibitory effect of isorhamnetin on IL-6 production. Isorhamnetin failed to prevent LPS from activating either c-Jun N-terminal kinase or p38 pathways. Isorhamnetin did not inhibit NF-κB transcriptional activity at the level of inhibitory κB-α degradation. Isorhamnetin suppressed NF-κB signaling through inhibition of nuclear translocation and DNA binding activity of NF-κB p50 subunit and attenuated signal transducer and activator of transcription 1 signaling.
CONCLUSION:
Although further research is required to clarify the detailed mechanism of action, we propose that isorhamnetin may contribute to blockade of the host-destructive processes mediated by IL-6 and could be a highly efficient modulator of the host response in the treatment of inflammatory periodontal disease. Further research in animal models of periodontitis is required to better evaluate, the potential of isorhamnetin as a novel agent for treating periodontal disease.
© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd....(more)
Jin JY, et al. J Periodontal Res 2013 Feb 27.
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- 35. Phenolic Composition Analysis and Gene Expression in Developing Seeds of Yellow- and Black- seeded Brassica napus.
Breeders have focused on yellow-seeded Brassica napus (rapeseed) for its better quality compared with the black-seeded variety. Moreover, flavonoids have been associated with this kind of rapeseed. In this study, we applied LC-ESI-MS<sup>n</sup> to compare flavonoids in developing seeds of natural black-seeded B. napus and yellow-seeded introgression lines selected from progenies of B. napus-Sinapis alba somatic hybrids. Aside from the most abundant phenolic compounds (sinapine and sinapic acid) and 1, 2-disinapoylglucose, 16 different flavonoids were identified and quantified, including (-)-epicatechin, five monocharged oligomers of (-)-epicatechin ([DP 2]<sup>-</sup> , [DP 3]<sup>-</sup> , [DP 4][DP 2]<sup>-</sup> B2 and [DP 2]<sup>-</sup> B5), quercetin, kaempferol, isorhamnetin-dihexoside, kaempferol-sinapoyl-trihexoside, isorhamnetin-sinapoyl-trihexoside, isorhamnetin-hexoside-sulfate, and isorhamnetin-3-O-glucoside. Most of the flavonoids accumulated with seed development, whereas some rapidly decreased during maturation. The content of these flavonoids were lower in the yellow-seeded materials than in the black seeds. In addition, variations of insoluble procyanidin oligomers and soluble phenolic acids were observed among both rapeseed varieties. Transcriptome changes of genes participating in the flavonoid pathway were discovered by qRT-PCR analysis. Consistent with flavonoid changes identified by HPLC analysis, the expression of most genes in the flavonoid biosynthetic pathway was also down-regulated....(more)
Jiang J, et al. J Integr Plant Biol 2013 Feb 27.
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