Jae-Hak Moon

Quercetin metabolites inhibit copper ion‐induced lipid peroxidation in rat plasma1

The oxidative susceptibility of plasma obtained from rats after intragastric administration of quercetin was studied to know whether or not quercetin acts as an in vivo antioxidant after metabolic conversion. Quercetin was raised in the rat blood plasma essentially as glucuronide and/or sulfate conjugates. The plasma obtained from rats after quercetin administration was more resistant against copper sulfate‐induced lipid peroxidation than the control plasma on the basis of the accumulation of cholesteryl ester hydroperoxides and the consumption of α‐tocopherol. The results strongly suggest that some conjugated metabolites of quercetin act as effective antioxidants when plasma is subject to metal ion‐induced lipid peroxidation.

Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway

We previously reported that quercetin, a bioflavonoid belonging to polyphenols, inhibited Angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) hypertrophy through the inhibition of c-Jun N-terminal kinase (JNK) activation. However, we recently found that orally administered quercetin appeared in plasma as glucuronide-conjugated forms in rats and humans. Therefore we examined the effect of chemically synthesized quercetin glucuronide on Ang II-induced mitogen-activated protein (MAP) kinase activation and hypertrophy of cultured rat aortic smooth muscle cells (RASMC). Ang II activated extracellular signal-regulated kinase (ERK)1/2, JNK, and p38 in RASMC. Ang II-induced JNK activation was inhibited by quercetin 3-O-beta-d-glucuronide (Q3GA) whereas ERK1/2 and p38 activations were not affected. Q3GA scavenged 1,1-diphenyl-2-picrylhydrazyl radical measured by a method of electron paramagnetic resonance. Q3GA also inhibited Ang II-induced increases in activator protein-1 (AP-1) DNA binding, a downstream transcription factor of JNK. Finally, Ang II-induced [3H]leucine incorporation into RASMC was abolished by Q3GA. These findings suggest that the preventing effect of Q3GA on Ang II-induced VSMC hypertrophy is attributable in part to its inhibitory effect on JNK and the AP-1 signaling pathway. Q3GA would be an active metabolite of quercetin in plasma and may possess a preventing effect for cardiovascular diseases relevant to VSMC growth.

Attenuation of lipid peroxidation and hyperlipidemia by quercetin glucoside in the aorta of high cholesterol-fed rabbit

Antioxidative activity of dietary flavonoids is suggested to be, at least partly, responsible for a wide variety of their biological effects relating to anti-atherosclerosis. However, it is not known whether dietary flavonoids reach to the target site and act as antioxidants. In this study, we tried to evaluate the antioxidative effect of quercetin 3-O-β-d-glucoside (Q3G), a typical flavonoid present in vegetables, in rabbit aorta. New Zealand White rabbits were fed a control diet (control group), 2.0% cholesterol diet (HC group) and 2.0% cholesterol plus 0.1% Q3G (HC + Q3G group) for one month. The amounts of total cholesterol, triacylglycerol and total fatty acids in both the plasma and aorta were significantly lower in the HC + Q3G group as compared with the HC group. Quercetin was detected in the aorta of the HC + Q3G group after enzymatic deconjugation, indicating that quercetin accumulated as conjugated metabolites in the aorta. The contents of TBA-reacting substances (TBARS) and cholesteryl ester hydroperoxides (CEOOH) in the aorta of the HC + Q3G group were significantly lower than those in the HC group. The aorta of HC + Q3G group was more resistant than that of HC group in copper ion-induced lipid peroxidation ex vivo. HC + Q3G group accumulated a higher amount of vitamin E per total cholesterol than HC group in the aorta. These results strongly suggest that quercetin glucosides accumulate in the aorta as their metabolites and attenuate lipid peroxidation occurring in the aorta, along with the attenuation of hyperlipidemia.

Protection by quercetin and quercetin 3-O-β-D-glucuronide of peroxynitrite-induced antioxidant consumption in human plasma low-density lipoprotein

Effect of quercetin and its conjugated metabolite quercetin 3-O-β-D-glucuronide (Q3GA), on peroxynitrite-induced consumption of lipophilic antioxidants in human plasma low-density lipoprotein (LDL) was measured to estimate the role of dietary flavonoids in the defense system against oxidative modification of LDL based on the reaction of nitric oxide and superoxide anion. Synthesized peroxynitrite-induced consumption of endogenous lycopene β-carotene and α-tocopherol was effectively suppressed by adding quercetin aglycone into LDL solution. Q3GA also inhibited the consumption of these antioxidants effectively. These results indicate that dietary quercetin is capable of inhibiting peroxynitrite-induced oxidative modification of LDL in association with lipophilic antioxidants present within this lipoprotein particle.

Effect of Quercetin and Its Conjugated Metabolite on the Hydrogen Peroxide-induced Intracellular Production of Reactive Oxygen Species in Mouse Fibroblasts

To clarify the antioxidative role of quercetin metabolites in cellular oxidative stress, we measured the inhibitory effects of the quercetin aglycon and quercetin 3-O-β-D-glucuronide (Q3GA), which is one of the quercetin metabolites in the blood after an intake of quercetin-rich food, on the production of hydrogen peroxide (H2O2)-induced intracellular reactive oxygen species in mouse fibroblast 3T3 cultured cells. When the cells were exposed to H2O2 in the presence of quercetin or Q3GA, Q3GA was found to be less effective than quercetin. In the case of a pretreatment with quercetin or Q3GA before the exposure, Q3GA, but not the quercetin aglycon, exerted an inhibitory effect, although its cellular uptake was unlikely. The quercetin aglycon appeared to fail in its antioxidative effect due to metabolic conversion into isorhamnetin conjugates, with substantial oxidative degradation resulting from the pretreatment. It is, therefore, suggested that quercetin metabolites take part in the protection of intracellular oxidative stress induced by the extraneous attack of H2O2.

Cognitive dysfunctions induced by a cholinergic blockade and Aβ25–35 peptide are attenuated by salvianolic acid B

Alzheimers disease (AD) is a neurodegenerative disorder associated with progressive cognitive and memory loss and neuronal cell death. Current therapeutic strategies for AD are very limited; thus, traditional herbal medicines or their active constituents receive much attention. The aim of this study was to investigate the cognitive enhancing effects of salvianolic acid B (SalB) isolated from Salvia miltiorrhiza and its ameliorating effects on various drug-induced amnesic models using the passive avoidance, Y-maze, and Morris water maze tasks. Drug-induced amnesia was induced by administering scopolamine, diazepam, muscimol, or amyloid-β (Aβ)(25-35) peptide. SalB (10 mg/kg, p.o.) was found to significantly reverse the cognitive impairments induced by scopolamine (1 mg/kg, i.p.) or Aβ(25-35) (10 nmol/5 μl, i.c.v.) injection. This ameliorating effect of SalB was antagonized by the GABA(A) receptor agonists, muscimol or diazepam, respectively. In addition, SalB alone was capable of improving cognitive performances. Furthermore, SalB (100 μM) was found to inhibit GABA-induced outward Cl(-) currents in single hippocampal CA1 neuron. These results suggest that the observed ameliorations of cholinergic dysfunction- or Aβ(25-35)-induced memory impairment by SalB were mediated, in part, via the GABAergic neurotransmitter system after a single administration.

Coumaroyl quinic acid derivatives and flavonoids from immature pear ( Pyrus pyrifolia nakai) fruit

Fourteen compounds were isolated from 60% ethanol extracts of immature pear (Pyrus pyrifolia Nakai cv. Chuhwangbae) fruit using Amberlite XAD-2 column HPLC with guided DPPH radical scavenging assay. Based on MS and NMR analysis, the isolated compounds were identified as 5-O-trans-caffeoyl quinic acid methyl ester (1), malaxinic acid (2), 5-O-trans-p-coumaroyl quinic acid methyl ester (3), 5-O-cis-p-coumaroyl quinic acid methyl ester (4), 5-O-trans-p-coumaroyl quinic acid (5), trans-p-coumaric acid (6), methyl cis-p-coumarate (7), methyl trans-p-coumarate (8), 3,5-O-dicaffeoyl quinic acid (9), (-)-epicatechin (10), (S)-(+)-2-cis-abscisic acid (11), isorhamnetin 3-O-β-d-galacto-pyranoside (12), isorhamnetin-3-O-β-d-glucopyranoside (13), and isorhamnetin 3-O-α-l-rhamnopyranosyl (1→6)-O-β-d-glucopyranoside (14). Six compounds (1, 2, 6, 9, 10, and 13) were identified previously, but other compounds (3–5, 7, 8, 11, 12, and 14) were isolated for the first time from pear.

Caffeoyl Triterpenes from Pear (Pyrus pyrifolia Nakai) Fruit Peels and Their Antioxidative Activities against Oxidation of Rat Blood Plasma

Six triterpenes, including three caffeoyl triterpenes, were purified and isolated from pear fruit ( Pyrus pyrifolia Nakai cv. Chuwhangbae) peel extracts using various column chromatography techniques with a guided 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay. The isolated compounds were identified as betulinic aldehyde (1), lupeol (2), betulinic acid (3), 3-O-cis-caffeoylbetulinic acid (4), 3-O-trans-caffeoylbetulinic acid (5), and 3-O-trans-caffeoyloleanolic acid (6) on the basis of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. Four compounds (1, 4-6) were identified from Asian pear fruit for the first time. In addition, compounds 4-6, containing a caffeic acid moiety, showed higher DPPH radical-scavenging and suppression effects against copper ion-induced oxidation of rat blood plasma than other compounds without a caffeic acid moiety.

Hydroxycinnamoylmalic acids and their methyl esters from pear (Pyrus pyrifolia Nakai) fruit peel.

Two novel caffeoylmalic acid methyl esters, 2-O-(trans-caffeoyl)malic acid 1-methyl ester (6) and 2-O-(trans-caffeoyl)malic acid 4-methyl ester (7), were isolated from pear (Pyrus pyrifolia Nakai cv. Chuhwangbae) fruit peels. In addition, 5 known hydroxycinnamoylmalic acids and their methyl esters were identified: 2-O-(trans-coumaroyl)malic acid (1), 2-O-(cis-coumaroyl)malic acid (2), 2-O-(cis-coumaroyl)malic acid 1-methyl ester (3), 2-O-(trans-coumaroyl)malic acid 1-methyl ester (4), and 2-O-(trans-caffeoyl)malic acid (phaselic acid, 5). The chemical structures of these compounds were determined by spectroscopic data from ESI MS and NMR. Of all the isolated compounds, five hydroxycinnamoylmalic acids and their methyl esters (2-4, 6, 7) were identified in the pear for the first time.

Roseomonas riguiloci sp. nov., isolated from wetland freshwater.

A non-motile, coccobacillus-shaped and pink pigmented bacterium, designated strain 03SU10-P(T), was isolated from wetland freshwater (Woopo wetland, Republic of Korea). Cells were Gram reaction-negative and catalase- and oxidase-positive. The major fatty acids (>10% of total) were C(18:1)ω7c and summed feature 3 (iso-C(15:0) 2-OH and/or C(16:1)ω7c). The predominant respiratory lipoquinone was Q-10. The DNA G+C content was 68 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylcholine and an unknown aminolipid. Spermidine, putrescine and 1,3-diaminopropane were the major polyamines. A phylogenetic tree based on 16S rRNA gene sequence comparisons showed that strain 03SU10-P(T) formed an evolutionary lineage within the radiation enclosing the members of the genus Roseomonas. The nearest neighbour to the novel strain was Roseomonas stagni HS-69(T) (96.3% gene sequence similarity). The evidence provided by the polyphasic taxonomic approach used in this study indicated that strain 03SU10-P(T) could not be assigned to any recognized species; therefore a novel species is proposed, Roseomonas riguiloci sp. nov., with 03SU10-P(T) ( = KCTC 23339(T) = JCM 17520(T)) as the type strain.