Hyoung Jae Lee

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.

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.

Chemical conversions of salvianolic acid B by decoction in aqueous solution

Salvianolic acid B (Sal B) is the most abundant phenolic compound in Salvia miltiorrhiza, which has been widely used for the treatment of cardiovascular diseases in Oriental medicine. To elucidate structure of the converted compounds of Sal B by decoction in aqueous solution, Sal B (200 mg) was decocted in an aqueous solution (200 mL) at pH 4.9 and the decocted solution was purified by Sephadex LH-20 column chromatography and preparative HPLC. The 13 converted compounds were isolated and the chemical structures were determined by NMR and MS. In addition to the 4 compounds previously reported as conversion products of Sal B by decoction, 9 compounds were first reported with the complete structure of compounds isolated from decocted Sal B solution and three of the compounds were determined to be novel compounds. In addition, a conversion mechanism of compounds converted by decoction was proposed on the basis of kinetics studies, which reasonably supported the conversion mechanism of Sal B. The 13 compounds seemed to be produced by the hydrolysis of an ester bond, decarboxylation, retro oxa-Michael reaction, hydration, and radical reaction during decoction in aqueous solution.

Isolation and Identification of Antioxidants from Makgeolli

The present study was carried out to isolate and identify of antioxidants from makgeolli. Makgeolli (3 L) was filtered and the residue was extracted by MeOH. The combined filtrates and MeOH extracts were successively solvent- fractionated by n-hexane, EtOAc, and BuOH. In the antioxidative activity against DPPH and ABTS + radicals of each fraction obtained after solvent-fractionation, EtOAc and BuOH layers showed higher activities than other fractions. Therefore, the two layers were respectively purified by column chromatography and HPLC. The isolated compounds were subjected to NMR and MS analyses and identified as 4-hydroxybenzaldehyde (1, 2.0 mg), 2-(4-hydroxyphenyl)ethanol (2, tyrosol, 15.3 mg), trans- and cis-ferulic acids (3 and 4, 1.2 mg), 1H-indole-3-ethanol (5, tryptophol, 3.4 mg), dimethyl succinate (6, 14.9 mg), succinic acid (7, 7.4 mg), and mono-methyl succinate (8, 7.8 mg). The presence of 1-5 in makgeolli have never before been reported.

Behavior of flavonoid glycosides contained in Korean red pepper paste (Gochujang) during fermentation: Participation of a β-glucosidase inhibitor

Gochujang is a red pepper-soybean paste and a popular Korean fermented food. The aim of this study was to investigate the behavior of flavonoids and activity of β-glucosidase during fermentation of gochujang prepared using Aspergillus oryzae. The content of flavonoid glycosides (genistin, daidzin, apigenin 7-O-β-d-glucopyranoside, and quercetin 3-O-α-l-rhamnopyranoside) and their aglycones did not change significantly during preparation of gochujang. However, β-glucosidase was produced by A. oryzae. The polar layer of the gochujang methanol (MeOH) extract more strongly inhibited the β-glucosidase activity of the crude enzyme extracted from gochujang than that of the nonpolar layer. The red pepper extract and high salt solution of the gochujang ingredients showed high β-glucosidase inhibition activity. These results indicate that flavonoid glycosides were not hydrolyzed by the β-glucosidase produced by A. oryzae during gochujang fermentation, which may have been due to the salt and hydrophilic compound(s) present in red pepper as main ingredients of gochujang.

Bioconversion of Capsaicin by Aspergillus oryzae

This study identified metabolites of capsaicin bioconverted by Aspergillus oryzae, which is generally used for mass production of gochujang prepared by fermenting red pepper powder in Korea. A. oryzae was incubated with capsaicin in potato dextrose broth. Capsaicin decreased depending on the incubation period, but new metabolites increased. Five capsaicin metabolites purified from the ethyl acetate fraction of the capsaicin culture were identified as N-vanillylcarbamoylbutyric acid, N-vanillyl-9-hydroxy-8-methyloctanamide, ω-hydroxycapsaicin, 8-methyl-N-vanillylcarbamoyl-6(E)-octenoic acid, and 2-methyl-N-vanillylcarbamoyl-6(Z)-octenoic acid by nuclear magnetic resonance (NMR) and mass spectrometry (MS). The capsaicin metabolites in gochujang were confirmed and quantitated by selective multiple reaction monitoring detection after liquid chromatography electrospray ionization MS using the isolated compounds as external standards. On the basis of the structures of the capsaicin metabolites, it is proposed that capsaicin metabolites were converted by A. oryzae by ω-hydroxylation, alcohol oxidation, hydrogenation, isomerization, and α- and/or β-oxidation.

Four New Dicaffeoylquinic Acid Derivatives from Glasswort (Salicornia herbacea L.) and Their Antioxidative Activity.

Four new dicaffeoylquinic acid derivatives and two known 3-caffeoylquinic acid derivatives were isolated from methanol extracts using the aerial parts of Salicornia herbacea. The four new dicaffeoylquinic acid derivatives were established as 3-caffeoyl-5-dihydrocaffeoylquinic acid, 3-caffeoyl-5-dihydrocaffeoylquinic acid methyl ester, 3-caffeoyl-4-dihydrocaffeoylquinic acid methyl ester, and 3,5-di-dihydrocaffeoylquinic acid methyl ester. Their chemical structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy (LC-ESI-MS). In addition, the presence of dicaffeoylquinic acid derivatives in this plant was reconfirmed by LC-ESI-MS/MS analysis. The isolated compounds strongly scavenged 1,1-diphenyl-2-picrylhydrazyl radicals and inhibited cholesteryl ester hydroperoxide formation during rat blood plasma oxidation induced by copper ions. These results indicate that the caffeoylquinic acid derivatives may partially contribute to the antioxidative effect of S. herbacea.

Change in the content of phenolic compounds and antioxidant activity during manufacturing of black raspberry (Rubus coreanus Miq.) wine

The changes in total phenolics, total anthocyanins, gallic acid (GA), and 3,4-dihydroxybenzoic acid (DHBA) contents during black raspberry (BR, Rubus coreanus) wine manufacturing were investigated. Total phenolic content gradually increased during BR wine manufacturing. The total anthocyanin content slightly increased, but the changes were not significant. The GA and DHBA in BR wine were detected as main compounds and their content greatly increased during manufacturing. The DPPH radical-scavenging activity was also increased during BR wine manufacturing. In particular, the antioxidant activity in the blood plasma of rats administered with BR wine concentrate was significantly higher than those administered with BR fruit extracts in inhibition of copper ion-induced cholesteryl ester hydroperoxide formation. These results indicate that an increase in antioxidant activity of BR wine may be due to low molecular phenolic compounds including GA and DHBA produced during the manufacturing.

Furan, phenolic, and heptelidic acid derivatives produced by Aspergillus oryzae

Eleven compounds, including a new sesquiterpene, were isolated from the culture medium of Aspergillus oryzae incubated with capsaicin. The structure of the new compound was determined to be 1,3,5a,6,7,8,9,9a-octahydro-9-hydroxy-9-(hydroxymethyl)-6-isopropyl-1-oxobenzo[c]oxepine-4- carboxylic acid, a heptelidic acid derivative. In addition, 10 known compounds were identified, namely 5-(hydroxymethyl)-3-furancarboxylic acid (flufuran), 3-hydroxypropanoic acid, 5-(hydroxymethyl)-2- furancarboxylic acid, 2-(4-hydroxyphenyl)-ethanol, 4-hydroxybenzoic acid, vanillic acid, 3,4-dihydroxybenzoic acid, 2-furanol, hydroheptelidic acid, and trichoderonic acid A, using spectroscopic data from nuclear magnetic resonance and electrospray ionization–mass spectroscopy.