Academic literature on the topic 'Isoferulic acid'

Tea and coffee are rich in polyphenols with a variety of biological activities. Many of the demonstrated activities are consistent with favourable effects on the risk of chronic diseases. 4-O-methylgallic acid (4OMGA) and isoferulic acid are potential biomarkers of exposure to polyphenols derived from tea and coffee respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid is derived from chlorogenic acid in coffee. Our major objective was to explore the relationships of tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid in human subjects. The relationships of long-term usual (111 participants) and contemporaneously recorded current (344 participants) tea and coffee intake with 24 h urinary excretion of 4OMGA and isoferulic acid were assessed in two populations. 4OMGA was related to usual (r 0·50, P<0·001) and current (r 0·57, P<0·001) tea intake, and isoferulic acid was related to usual (r 0·26, P=0·008) and current (r 0·18, P<0·001) coffee intake. Overall, our present results are consistent with the proposal that 4OMGA is a good biomarker for black tea-derived polyphenol exposure, but isoferulic acid may be of limited usefulness as a biomarker for coffee-derived polyphenol exposure.

Antioxidant and antiradical activities of ferulates (i.e., ferulic acid, isoferulic acid, coniferyl aldehyde, and methyl ferulate) were investigated using a &beta;-carotene-linoleate model system and a DPPH radical scavenging assay, respectively. Compounds so tested exhibited antioxidant and antiradical properties to varying degrees. Methyl ferulate showed the strongest antioxidant activity, whereas the parent phenolic acid was the most active ferulate to scavenge the DPPH radical (DPPH^&middot;). Isoferulic acid at concentrations ranging from 10 to 100 nmol/assay did not impart an antiradical efficacy; this may be attributed to the location of the hydroxyl group in the meta position on the aromatic ring. &nbsp;

Isoferulic acid (3-hydroxy-4-methoxycinnamic acid, IFA), the isomer of ferulic acid (4-hydroxy-3-methoxycinnamic acid), is a rare phenolic acid occurring in Rhizoma Cimicifugae. Unlike ferulic acid, which has been well investigated, the antioxidant activity of IFA has not been measured. In this study, IFA was systematically evaluated for its in vitro antioxidant activity for the first time. IC50 values were calculated of 7.30±0.57, 4.58±0.17, 1.08±0.01, 8.84±0.43, 7.69±0.39, 1.57±0.2, 13.33±0.49 μg/mL, respectively, for lipid peroxidation, DPPH (1,1-diphenyl-2-picrylhydrazyl radical) and ABTS (3-ethylbenzthiazoline-6-sulfonic acid diammonium salt) radical scavenging, reducing power on Fe3+ and Cu2+ ions, and hydroxyl and superoxide anion radical scavenging. Comparison with the IC50 values with those of the positive controls, Trolox and butylated hydroxyanisole (BHA), it can be concluded that isoferulic acid is an effective natural antioxidant in both lipid and aqueous media.

Abstract Caffeoyltartronic acid and other eleven phenolic com pounds were identified in the MeOH extract of Chondrilla juncea: the flavonoids luteolin, luteolin-7-glucoside, luteolin-7-galactosylglucuronide and quercetin-3-galactoside; the phenolic acids protocatechuic, caffeic, chlorogenic, isochlorogenic and isoferulic and the coumarins cichoriin and aesculetin. The taxonomic im plications of these com pounds have been discussed.

The Mg(II) and heterometallic Mn(II)/Na(I) complexes of isoferulic acid (3-hydroxy-4-methoxycinnamic acid, IFA) were synthesized and characterized by infrared spectroscopy FT-IR, FT-Raman, electronic absorption spectroscopy UV/VIS, and single-crystal X-ray diffraction. The reaction of MgCl2 with isoferulic acid in the aqueous solutions of NaOH resulted in synthesis of the complex salt of the general formula of [Mg(H2O)6]⋅(C10H9O4)2⋅6H2O. The crystal structure of this compound consists of discrete octahedral [Mg(H2O)6]2+ cations, isoferulic acid anions and solvent water molecules. The hydrated metal cations are arranged among the organic layers. The multiple hydrogen-bonding interactions established between the coordinated and lattice water molecules and the functional groups of the ligand stabilize the 3D architecture of the crystal. The use of MnCl2 instead of MgCl2 led to the formation of the Mn(II)/Na(I) complex of the general formula [Mn3Na2(C10H7O4)8(H2O)8]. The compound is a 3D coordination polymer composed of centrosymmetric pentanuclear subunits. The antioxidant activity of these compounds was evaluated by assays based on different antioxidant mechanisms of action, i.e., with •OH, DPPH• and ABTS•+ radicals as well as CUPRAC (cupric ions reducing power) and lipid peroxidation inhibition assays. The pro-oxidant property of compounds was measured as the rate of oxidation of Trolox. The Mg(II) and Mn(II)/Na(I) complexes with isoferulic acid showed higher antioxidant activity than ligand alone in DPPH (IFA, IC50 = 365.27 μM, Mg(II) IFA IC50 = 153.50 μM, Mn(II)/Na(I) IFA IC50 = 149.00 μM) and CUPRAC assays (IFA 40.92 μM of Trolox, Mg(II) IFA 87.93 μM and Mn(II)/Na(I) IFA 105.85 μM of Trolox; for compounds’ concentration 10 μM). Mg(II) IFA is a better scavenger of •OH than IFA and Mn(II)/Na(I) IFA complex. There was no distinct difference in ABTS•+ and lipid peroxidation assays between isoferulic acid and its Mg(II) complex, while Mn(II)/Na(I) complex showed lower activity than these compounds. The tested complexes displayed only slight antiproliferative activity tested in HaCaT human immortalized keratinocyte cell line within the solubility range. The Mn(II)/Na(I) IFA (16 μM in medium) caused an 87% (±5%) decrease in cell viability, the Mg salt caused a comparable, i.e., 87% (±4%) viability decrease in a concentration of 45 μM, while IFA caused this level of cell activity attenuation (87% ± 5%) at the concentration of 1582 μM (significant at α = 0.05).

To pursue an effective method to control phytoplankton blooms, the allelochemicals of Typha angustifolia L. were purified and identified and their allelopathic effects were studied in phytoplankton assemblage assays. We found that the Typha angustifolia L. allelochemicals included 3 phenic acids (o-hydroxycinnamic acid, syringic acid and isoferulic acid, which inhibited the growth of phytoplankton assemblage and the o-hydroxycinnamic acid proved most potent. The combined activity of these phenic acids exerted synergistic inhibitory effects on the growth of phytoplankton assemblage. The results suggested that Typha angustifolia L. and its allelochemicals may control the phytoplankton blooms in eutrophic waters.

From the chloroform and ethyl acetate extracts of the leaves of Kalanchoe pinnata L. (Crassulaceae), two flavonoids and three phenolic compounds were isolated; named quercetin (1), 5,7,4’-trihydroxy-8,3’-dimethoxyflavone (2), gallic acid (3), ferulic acid (4) and isoferulic acid (5). Based on the NMR spectroscopy, their chemical structures were elucidated and the result was confirmed by comparison with published data.

Wholegrain oats contain a variety of phenolic compounds thought to help maintain healthy vascular function, through the maintenance of local levels of the vasodilator nitric oxide (NO). Thus, the full molecular mechanisms involved are not yet clear. With this work we aim to understand the possible cellular mechanisms by which avenanthramides and ferulic acid derivatives, present in oats, may help maintain a healthy vascular function through the modulation of the NO pathway. Primary Human Umbilical Vein Endothelial Cells (HUVEC) were exposed to ferulic acid, isoferulic acid, hydroferulic acid, ferulic acid 4-O-glucuronide, isoferulic acid 3-O-sulfate, dihydroferulic acid 4-O-glucuronide, avenanthramide A, avenanthramide B and avenanthramide C (1 μM) or vehicle (methanol) for 24 h. Apocynin and Nω-Nitro-L-arginine (L-NNA) were additionally included as controls. NO and cyclic GMP (cGMP) levels, superoxide production and the activation of the Akt1/eNOS pathway were assessed. The statistical analysis was performed using one-way ANOVA followed by a Tukey post-hoc t-test. Apocynin and all phenolic compounds increased NO levels in HUVEC cells (increased DAF2-DA fluorescence and cGMP), and significantly reduced superoxide levels. Protein expression results highlighted an increase in the Akt1 activation state, and increased eNOS expression. Overall, our results indicated that the glucuronide metabolites do not enhance NO production through the Akt1/eNOS pathway, thus all compounds tested are able to reduce NO degradation through reduced superoxide formation.

Tea and coffee are rich in polyphenols with a variety of biological activities. Polyphenols found in tea are predominantly flavonoids, of which up to 15% are present as free or esterified gallic acid. Coffee polyphenols are almost wholly comprised of chlorogenic acids. Many of the demonstrated activities of polyphenols are consistent with favourable effects on the risk of chronic diseases. In investigating the relationships between intake and exposure to such compounds and chronic disease-related endpoints, it is important to be able to identify biomarkers that are specific to the compounds of interest. 4-O-methyl gallic acid (4OMGA) and isoferulic acid have been identified as potential biomarkers of intake and exposure to polyphenols derived from tea and coffee, respectively. 4OMGA is derived from gallic acid in tea, and isoferulic acid from chlorogenic acid in coffee. The major objectives of the research which is the subject of this thesis were (1) to establish a dose-response relationship of 24h urinary excretions of 4OMGA and isoferulic acid following ingestions of black tea and coffee of different strengths, and (2) to explore relationships of tea and coffee intake with 24h urinary excretion of 4OMGA and isoferulic acid in human populations. It was found that there was rapid excretion of both 4OMGA and isoferulic acid in the first 6h after tea and coffee ingestion, respectively. Approximately 60 80% of the ingested dose was excreted during the first 6h after ingestion. Urinary excretion of 4OMGA and isoferulic acid was directly related to the dose of tea and coffee, respectively. That is, higher intake resulted in increased urinary excretion of the metabolites. The relationships of 24h urinary excretion of 4OMGA and isoferulic acid with long-term usual (111 participants) and contemporary recorded current (344 participants) tea and coffee intake were assessed. 4OMGA was strongly related to usual (r = 0.50, P < 0.001) and current (r = 0.57, P < 0.001) tea intake. Isoferulic acid was less strongly, but significantly associated with usual (r = 0.26, P = 0.008) and current (r = 0.18, P < 0.001) coffee intake. Overall, the results are consistent with the proposal that 4OMGA is a good biomarker for black tea derived polyphenol intake and exposure, but isoferulic acid may have only limited use as a biomarker for coffee-derived polyphenol exposure.

碩士
台北醫學院
藥學研究所
88
Abstract Isoferulic acid is the major constituent of Cimicifugae rhizoma and Clematidis radix. In previous papers, isoferulic acid has been demonstrated to have anti-inflammatory, hypothermic, antipyretic, antiedematous, and anti-hyperglycemic effects. Although isoferulic acid has several pharmacological actions, the pharmacokinetics of isoferulic acid has not been studied. The aim of this studies was to investigate the pharmacokinetics of isoferulic acid in the rabbits. An accuracy, simple and specific high performance liquid chromatographic (HPLC) method was developed to detect the isoferulic acid in biological sample firstly. A C18 reverse phase column with UV detection at 320 nm was used in chromatographic separation. The calibration curve of plasma sample shows good linearity within the concentration range of 0.01 to 50 g/ml ; the calibration curve of urine sample also shows good linearity within the concentration range of 0.05 to 100 g/ml. The coefficients of variation (C.V.) of the within-run and between-run validation are all within 15%. The stability of isoferulic acid in various pH buffer solutions were investigated. The result shows that isoferulic acid was very stable in pH 2.66  9.60 at room temperature (25C), and there was no degradation of isoferulic acid. Besides, the stability of isoferulic acid in urine under air was also very stable and no degradation. The pharmacokinetics of isoferulic acid was studied by intravenous administration of three different doses (2, 5, 25 mg/kg) in six rabbits, respectively. The plasma concentration-time profiles of isoferulic acid could be descried by a bi-exponential equation with each dose. The elimination half-life are 13.883.95, 13.331.91, 14.000.95 minutes , and systemic clearance(ClT) are 23.75 4.83, 20.922.13, 21.332.87 ml/min. There are no significant difference in elimination half-life and systemic clearance of isoferulic acid under these three doses. The area under the curves (AUCs) calculated from time zero to infinite are 88.6022.78, 266.5436.86, 1382.67172.19 gmin/ml. It is proportional to the dose administrated. It indicated that isoferulic acid may be have dose-independent pharmacokinetics between 2 ~ 25 mg/kg IV injection. In addition, 25 mg/kg of isoferulic acid was oral administration to six rabbits. The concentration-time profiles of plasma could be fitted by one-compartment model or two-compartment model. The area under the curves (AUCs) was 306.9024.22 gmin/ml. Comparing with that of intravenous administration in the dose of 25 mg/kg , the absolute bioavailability of isoferulic acid was 0.220.03 through the oral administration. On the other hand, the ratio of isoferulic acid excreted from kidney was less than 1%, but percentages of glucuronidation for isoferulic acid is more than 37.4912.25%. It shows that first-pass effect of liver and other tissue were major pathway of metabolism for isoferulic acid instead of kidney.

博士
國立成功大學
基礎醫學研究所
89
Diabetes mellitus (DM) is one of the serious disorders around the world. Cimicifuga rhizoma is contained in the prescription of “Bu-Zhong-I-Chi-Tang”, a medication to be effective for the handling of DM in traditional Chinese medicine. Isoferulic acid is one of the active prinicles in Cimicifuga rhizoma. The present study is performed to investigate the antihyperglycemic action of isoferulic acid. A dose-dependent lowering of plasma glucose was obtained in the fasting rats with insulin dependent DM, both Bio—Breeding/Worcester rats and steptozotocin-induced diabetic rats (STZ-diabetic rats). However, plasma glucose levels in normal and non-insulin dependent DM rats can be lowered by isoferulic acid at a higher dose. Isoferulic acid at the effective dose significantly attenuated the increase of plasma glucose induced by intravenous glucose challenge test in Wistar rats. Isoferulic acid enhanced the uptake of radioactive glucose into mouse myoblast cells, C2C12 cells, in a concentration-dependent manner. Effect of isoferulic acid on a1-adrenoceptors was supported by the displacement of [3H]YM617 binding in C2C12 cells. The action of isoferulic acid to enhance the uptake of radioactive glucose was abolished in C2C12 cells pre-incubated with the antagonist at concentrations sufficient to block a1A-adrenoceptor (a1A-AR). The plasma glucose lowering effect of isoferulic acid in the STZ-diabetic rats was also abolished by pretreatment with a1A-AR antagonists. Pharmacological inhibition of phospholipase C (PLC) resulted in a concentration-dependent reduction of the isoferulic acid-stimulated uptake of radioactive glucose into C2C12 cells. Moreover, chelerythrine and GF 109203X diminished the action of isoferulic acid at concentration sufficient to inhibit protein kinase C (PKC).The obtained data suggest that activation of a1A-AR may play an important role in the plasma glucose lowering activity of isoferulic acid in the absence of insulin. Injection of isoferulic acid at the effective dose increased the plasma b-endorphin-like immunoreactivity (BER) in STZ-diabetic rats that can be abolished by a1A-AR. Treatment with b-endorphin enhanced the uptake of radioactive glucose in a concentration-dependent manner in skeletal muscle and hepatocytes isolated from STZ-diabetic rats. The plasma glucose lowering effect of isoferulic acid was also abolished by pretreatment with naloxone or naloxonazine at doses sufficient to block opioid m-receptors. Plasma glucose lowering action of isoferulic acid disappeared in opioid m-receptors knockout mice, while the plasma glucose lowering response to isoferulic acid was still observed in wild-type mice. Mediation of opioid m-receptors in the plasma glucose lowering action of isoferulic acid can thus be considered. In addition, isoferulic acid enhanced the BER secretion from isolated adrenal medulla of STZ-diabetic rats in a concentration-dependent manner and the antagonists of a1A-AR abolished this action. In the presence of PLC inhibitor, isoferulic acid-induced change of BER was reduced in a concentration-dependent manner. Moreover, pharmacological inhibition of PKC diminished this action of isoferulic acid. Bilateral adrenalectomy made the loss of the plasma glucose lowering action of isoferulic acid and no increase of plasma BER was obtained in isoferulic acid treated STZ-diabetic rats. The mRNA and protein levels of glucose transporter subtype 4 form (GLUT4) in skeletal muscle was increased by isoferulic acid after repeated treatment for 1 day in STZ-diabetic rats. Otherwise, similar repeated treatment with isoferulic acid reversed the elevated mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) in liver of STZ-diabetic rats to the normal level. Pharmacological inhibition of a1A-AR or opioid m-receptors resulted in the loss of isoferulic acid-induced action. These results suggest that release of b-endorphin from the adrenal gland seems responsible for the lowering of plasma glucose in STZ-diabetic rats by isoferulic acid through an activation of a1A-AR. Activation of opioid m-receptors by the released b-endorphin can increase the utilization of glucose and/or decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin.

碩士
台北醫學院
藥學研究所
89
Recently, isoferulic acid isolated from the rhizome of Cimicjfuga dahurica Maxim.(Ranunculaceae) has been identified to have in vivo antihyperglycemic activity in our laboratory. The effect for lowering of plasma glucose by isoferulic acid in IDDM rats is more active than that in NIDDM rats. Furthermore, the plasma glucose in normal rats is not markedly influenced by isoferulic acid under similar treatment. The antihyperglycemic mechanism is through the enhancement of glucose utilization in peripheral tissues and a reduction of hepatic gluconeogenesis. In order to study the structure and activity relationship (SAR) of isoferulic acid (1), a series of isoferulic acid analogues are prepared and their antidiabetic activities are evaluated. Isoferulic acid (1) and its 3-O-alkyl analogues are prepared by Knoevenagel condensation. Condensation of malonic acid with various 3-O-alkyl benzaldehydes (e.g. isovanillin, veratraldehyde, piperonal, compound 5, 7, and 9) in the presence of pyridine and a trace of piperidine gave the 3-O-alkyl analogues 1, 3, 4, 6, 8, and 10. The 3-O-acyl analogues, 11 and 12, are prepared by isoferulic acid and anhydrides in acid medium. The 4-O-alkyl analogues 14 and 16 are prepared by condensation of various 4-O-alkyl benzaldehydes (13 and 15) and malonic acid. The ester analogues 17∼19 are prepared by esterification of isoferulic acid with various alcohols. Condensation of 3-hydroxy-4-methoxycinnamoyl chloride with various primary and secondary amines gave the amide analogues 20∼25. The cis-form analogue 26 is generated by photochemical reaction with direct UV irradiation of the trans-isoferulic acid. Catalytic hydrogenation of isoferulic acid gave the dihydroisoferulic acid 27. Cyclopropane analogue 29 was prepared by treated isoferulic acid methyl ester (17) with diazomethane and palladium (II) acetate followed with hydrolysis. The α-methyl analogue 30 is prepared by the condensation of methyl malonic acid and 3-hydroxy-4-methoxybenzaldehyde. Twenty three products were prepared including 1, 3, 4, 6, 8, 10∼12, 14, 16∼27, 29, and 30. All these analogues were characterized by M.P., IR, 1H-NMR, mass spectrometry, 13C-NMR and element analysis. Initially, 15 analogues including 1∼4, 6, 11, 16, 17, 20, 22, 24, 25, 27, 29, and 30 were selected to evaluate their antidiabetic activities. The glucose uptake study of soleus muscle cells from streptozotocin induced diabetic rats shows that 6, 11, 16, 22, and 24 were more active than that of isoferulic acid (1). Among these compounds, 6 and 11 have the most remarkable antidiabetic activities. The preliminary results of structure and activity relationships show that the 4-OCH3 on aromatic ring and the unsaturated double bond are essential for antidiabetic activities. The tertiary amides, the 3-O-ethyl or 3-O-acetyl substitutions also enhance the activity.

碩士
臺北醫學大學
藥學研究所
97
Caffeic acid (CA), ferulic acid (FA) and isoferulic acid (IFA) are naturally occurring phenolic cmpounds and they have similar chemical structures. CA is the derivative of catechol, and FA and IFA are the methylation products of CA on meta- and para-position of catechol functional group, respectively. Therefore, the aim of this study was to investigate the structure-relationship pharmacokinetics of CA, FA and IFA in the rabbits. CA, FA and IFA were given intravenously with a dose of 10 mg/kg to six male New Zealand white rabbits, respectively, in a crossover treatment. Pharmacokinetic parameters were determined with plasma concentration of CA, FA and IFA by noncompartmental method. After intravenous administration of CA at a dose 10 mg/kg in rabbits, the AUC0-∞, elimination half-life (t1/2) and clearance of CA were 377.80 ± 72.32 μg/mL×min, 24.77 ± 10.08 min and 27.26 ± 5.03 mL/min/kg, respectively. The AUC0-∞ of FA and IFA transformed from CA were 57.38 ± 15.05 μg/mL×min and 6.08 ± 1.15 μg/mL×min, and the elimination half-life (t1/2) of FA and IFA were 15.85 ± 3.39 and 17.57 ± 1.95 min. After intravenous administration of FA at a dose 10 mg/kg in rabbits, the AUC0-∞, elimination half-life (t1/2) and clearance of of FA was 577.39 ± 76.64 μg/mL×min, 14.87 ± 2.77 min and 17.56 ± 2.21 mL/min/kg, respectively. After intravenous administration of IFA at a dose 10 mg/kg in rabbits, the AUC0-∞, elimination half-life (t1/2) and clearance of of of IFA was 513.98 ± 179.16 μg/mL×min, 17.16 ± 2.27 min and 21.45 ± 7.24 mL/min/kg, respectively. Inaddition, the percentage of CA, FA and IFA excreted in the urine with unchanged form were 46.93 ± 17.17, 27.63 ± 10.13 and 1.77 ± 1.24(%), respectively. On the other hand, CA, FA and IFA excreted with conjugated form (glucuronidation plus sulfation) were 27.50 ± 5.59%、27.65 ± 10.02%及35.61 ± 8.98%, respectively. Percent glucuronidation of CA, FA and IFA were 13.62 ± 3.81%、16.12 ± 6.86%及15.06 ± 3.38%, respectively, and percent sulfation of CA, FA and IFA were 13.88 ± 2.92%、11.53 ± 3.95%及20.55 ± 5.69%, respectively. After intravenous administration of CA, the percentage of CA excreted in urine as FA and IFA were 15.16± 9.53 and 0.29 ± 0.13(%), respectively. It indicated the formation ratio of FA was much higher than that of IFA, after administration of CA. It indicated that methylation of CA had regioselectivity. However, the percentage of IFA and FA excreted in urine as CA were negligible.