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Biomedical subjects

Hyeong-Kyu Lee

Publications and source records attributed to Hyeong-Kyu Lee.

At least 19 recordsLinked to original sources

Inhibitory effects of tilianin on the expression of inducible nitric oxide synthase in low density lipoprotein receptor deficiency mice.

We investigated the effect of tilianin upon inducible nitric oxide synthesis in the plasma of low-density lipoprotein receptor knock-out (Ldlr-/-) mice fed with high cholesterol diet and in primary peritoneal macrophages of Ldlr-/- mice. High cholesterol diet induced nitric oxide production in the plasma of Ldlr-/- mice. Tilianin reduced the level of nitric oxide (NO) in plasma from Ldlr-/- mice induced by the high cholesterol diet. Tilianin also inhibited the NO production from the primary culture of peritoneal macrophages treated with lipopolysaccharide. The inhibition of NO production was caused by the suppression of inducible nitric oxide synthase (iNOS) gene expression in peritoneal macrophages isolated from Ldlr-/- mice. Moreover, tilianin inhibited the transcriptional activation of iNOS promoter that has NF-kappaB binding element. Thus, these results provide the first evidence that tilianin inhibit iNOS expression and production of NO and may act as a potential anti-inflammatory agent.

Animals↗

Two novel furan derivatives from Phellinus linteus with anti-complement activity.

Two novel stereoisomers of furan derivatives, phellinusfurans A (1) and B (2), were isolated from the fruiting body of Phellinus linteus. Their structures were elucidated by spectroscopic analysis. Compounds 1 and 2 exhibited significant anti-complement activity with IC50 values of 33.6 and 33.7 microM, respectively, in inhibiting the hemolytic activity of human serum against erythrocytes.

Basidiomycota↗

Suppressive effect of verproside isolated from Pseudolysimachion longifolium on airway inflammation in a mouse model of allergic asthma.

Allergic inflammation of the airways has a critical role in asthma development. We investigated a suppressive effect of verproside (3,4-dihydroxy catalpol) isolated from the extract of Pseudolysimachion longifolium on asthmatic parameters--such as immunoglobulin E (IgE) level, cytokine release, eosinophilia, airway hyperresponsiveness and mucus hypersecretion--in an OVA-sensitized/challenged mouse model. Verproside significantly inhibited the increase of total IgE and the cytokines IL-4 and IL-13 in plasma and bronchoalveolar lavage fluid, and also effectively suppressed airway hyperresponsiveness, eosinophilia and mucus hypersecretion in OVA-induced asthmatic mice. The efficacy of verproside was comparable to montelukast, an anti-asthmatic drug that is currently available. These results suggest that verproside could be a major marker in herbal medicines that are used for asthma treatment, and could also act as a lead for anti-asthmatic drugs.

Acetates↗

Isolation of flavonoids, a biscoumarin and an amide from the flower buds of Daphne genkwa and the evaluation of their anti-complement activity.

As part of an ongoing study aimed at identifying the anti-complement active compound from the flower buds of Daphne genkwa, ten flavonoids, one biscoumarin and one amide were isolated. Their structures were identified from spectroscopic and physicochemical data as genkwanin 5-O-beta-d-primveroside (1), apigenin 7-O-beta-d-glucuronide (2), genkwanin 5-O-beta-d-glucopyranoside (3), apigenin 5-O-beta-d-glucopyranoside (4), genkwanin (5), apigenin (6), luteolin 7-methyl ether (7), luteolin (8), daphnoretin (9), velutin (10), 7-methoxyacacetin (11) and aurantiamide acetate (12). Among them, compounds 9, 10 and 12 were isolated from this plant for the first time. The anti-complement activity of these compounds was tested against the classical pathway of the complement system. Among the compounds, daphnoretin (9) exhibited significant anti-complement activity with an IC(50) value of 11.4 microm, whereas the other compounds were not active in the assay.

Amides↗

Anticomplement activity of cycloartane glycosides from the rhizome of Cimicifuga foetida.

A tetranor-cycloartane glycoside and two 9,19-cycloartane glycosides were isolated from the EtOAc-soluble fraction of the rhizome of Cimicifuga foetida. The structures of the compounds were determined to be cimilactone A (1), 25-O-acetylcimigenol 3-O-beta-d-xylopyranoside (2) and cimigenol 3-O-alpha-l-arabinopyranoside (3), respectively, using spectroscopic analysis. The three compounds were examined for their anticomplement activity against the classical pathway of the complement system. Compound 1 showed significant anticomplement activity with an IC(50) value of 28.6 microm, whereas compounds 2 and 3 were inactive.

Animals↗

Anti-complementary activity of ursane-type triterpenoids from Weigela subsessilis.

A new ursane-type triterpenoid, weigelic acid (1), and seven known compounds, ursolic acid (2), ilekudinol A (3), corosolic acid (4), ilekudinol B (5), esculentic acid (6), pomolic acid (7), and asiatic acid (8) were isolated from the leaf and stem of Weigela subsessilis. The structure of the new triterpenoid was established as 1beta,2alpha,3alpha,23-tetrahydroxyurs-12-en-28-oic acid on the basis of spectroscopic analyses. In addition, the isolated compounds were evaluated for their anti-complement activity against the classical pathway of the complement system. Of these, compounds 1-2 and 4-8 exhibited anti-complement activity with IC50 values of 152, 90, 130, 51, 56, 4, and 163 microM, respectively, whereas 3 was inactive. This shows that a carboxylic group of ursane-type triterpenoids seems to play an important role in inhibiting the hemolytic activity of human serum against erythrocytes.

Animals↗

The effect of sativan from Viola verecunda A. Gray on the expressions of matrix metalloproteinase-1 caused by ultraviolet irradiated cultured primary human skin fibroblasts.

Matrix metalloproteinases (MMPs) are a family of enzymes whose main function is degradation of the extracellular matrix. Matrix metalloproteinase-1 (MMP-1) degrades type I procollagen constituting the major structural component of the basement membrane and extra cellular membrane. The enzymatic activity is found to be elevated in photoaging. With the aim of finding novel MMP-1 inhibitors from natural products, 15 extracts of the Viola taxa, which are used as prescriptions for skin eruption treatment in traditional medicine, were screened for their inhibitory activities towards MMP-1. Among the 15 tested materials, the methanol extracts of Viola hondoensis W. BECKER et H. BOISS, Viola ibukiana MAKINO, Viola lactiflora NAKAI and Viola verecunda A. GRAY were potential inhibitory to MMP-1, and other Viola taxa showed a weak inhibitory effect at a concentration of 100 microg/ml. We investigated the effect of MMP-1 inhibitory of the solvent fractions of the same plants (Viola hondoensis, Viola ibukiana and Viola verecunda). Therefore, a strong inhibition was found in the ethylacetate fractions of Viola verecunda with inhibitory activity (>90%) at a concentration of 10 microg/ml. Here we investigated the effect of sativan isolated from the ethylacetate fractions of Viola verecunda on the expression of MMPs in UV-irradiated human skin fibroblasts in vitro. Sativan markedly reduced UV-induced MMP-1 expression at the protein levels in a dose-dependent manner. Our report is the first description for the ability of sativan to regulate UV-induced MMP-1 expression.

Cells, Cultured↗

Flavonoids from the leaves of Litsea japonica and their anti-complement activity.

Four flavonoids, epicatechin (1), afzelin (2), quercitrin (3), and tiliroside (4), were isolated from the leaves of Litsea japonica (Thunb.) Jussieu (Lauraceae). The structures of compounds were identified by comparing their chemical and spectral data with those previously reported. The flavonoids (1-4) were tested for their anti-complement activity against classical pathway of complement system. Compounds 2-4 showed inhibitory activity against complement system with IC50 values of 258, 440, and 101 microm, respectively, whereas 1 was inactive. For the evaluation of the structure-activity relationship of 5,7-dihydroxyflavones, myricitrin (5) from Juglans mandshurica also tested for it's anti-complement activity and is inactive in this assay system. Furthermore, compounds 2, 3, and 5 were hydrolyzed with naringinase to give kaempferol (2a), quercetin (3a), and myricetin (5a), and these were also tested for their activity. Of the three aglycones, 2a exhibited anti-complement activity with an IC50 value of 730 microM, while 3a and 5a were inactive. The inhibitory potencies of 2, 2a, 3, 3a, 5, and 5a against complement activity increased in inverse proportion to number of free hydroxyls on B-ring of 5,7-dihydroxyflavone. Of the compounds tested, 4 showed the most potent inhibitory activity against the complement system.

Complement Inactivator Proteins↗

Neuroprotective and free radical scavenging activities of phenolic compounds from Hovenia dulcis.

The EtOAc-soluble fraction from a methanolic extract of Hovenia dulcis Thunb. exhibited neuroprotective activity against glutamate-induced neurotoxicity in mouse hippocampal HT22 cells. The neuroprotective activity-guided isolation resulted in 8 phenolic compounds (1-8), such as vanillic acid (1), ferulic acid (2), 3,5-dihydroxystilbene (3), (+)-aromadendrin (4), methyl vanillate (5), (-)-catechin (6), 2,3,4-trihydrobenzoic acid (7), and (+)-afzelechin (8). Among these, compounds 6 and 8 had a neuroprotective effect on the glutamate-induced neurotoxicity in HT22 cells. Furthermore, compound 6 had a DPPH free radical scavenging effect with an IC50 value of 57.7 microM, and a superoxide anion radical scavenging effect with an IC50 value of 8.0 microM. Both compounds 6 and 8 had ABTS cation radical scavenging effects with IC50 values of 7.8 microM and 23.7 microM, respectively. These results suggest that compounds 6 and 8 could be neuroprotectants owing to their free radical scavenging activities.

Animals↗

A new furofuran lignan with antioxidant and antiseizure activities from the leaves of Petasites japonicus.

A new furofuran lignan (1) was isolated from the n-butanol fraction of the methanolic extract of the leaves of Petasites japonicus (Sieb. et Zucc.) Maxim. (Compositae). The structure of compound 1 was determined to be 2alpha-(4'-hydroxy-3'-methoxyphenyl)-6alpha-(4"-hydroxy-3"-methoxyphenyl)-8alpha-hydroxy-3,7-dioxabicyclo[3.3.0octane 4'-O-(beta-D-glucopyranoside) by spectroscopic methods including 2D-NMR. In further studies, it was found that the compound 1 expressed an antioxidant activity in DPPH radical scavenging assay, and moreover, ameliorated the seizure in kainic acid-treated mice.

Animals↗

Wogonin inhibits excitotoxic and oxidative neuronal damage in primary cultured rat cortical cells.

The present study evaluated effects of wogonin (5,7-dihydroxy-8-methoxyflavone) on excitotoxic and oxidative stress-induced neuronal damage in primary cultured rat cortical cells. Wogonin was shown to inhibit the excitotoxicity induced by glutamate or N-methyl-D-aspartic acid, whereas it showed no effects on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- or kainate-induced toxicity. In addition, wogonin inhibited the oxidative neuronal damage induced by H(2)O(2), xanthine/xanthine oxidase, and by a glutathione depleting agent D,L-buthionine [S,R]-sulfoximine. Furthermore, wogonin dramatically inhibited lipid peroxidation initiated by Fe(2+) and L-ascorbic acid in rat brain homogenates. It also exhibited 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together, these results demonstrate that wogonin exhibits neuroprotective actions in cultured cortical cells by inhibiting excitotoxicity and various types of oxidative stress-induced damage, and that its antioxidant actions with radical scavenging activity may contribute, at least in part, to the neuroprotective effects.

Animals↗

Isolation and anticomplement activity of compounds from Dendropanax morbifera.

Dendropanax morbifera Leveille (Araliaceae) is used in Korea for a variety of disease, such as migraine headache and dysmenorrhea. A new polyacetylene (1) and six known compounds (2-7) were isolated from the leaves of this plant by conventional chromatographic techniques. The structure of the new polyacetylene (1) was determined as (9Z,16S)-16-hydroxy-9,17-octadecadiene-12,14-diynoic acid by spectroscopic means including 2D NMR, which comprised the determination of a chiral by modified Mosher's ester method. Compounds 1-7 were investigated in vitro for their anticomplement activity against the classical pathway of the complement system. Of these, compound 1 showed significant anticomplement activity with 50% inhibitory concentration (IC50) value of 56.98 microM, whereas compounds 2-7 were inactive.

Araliaceae↗

New furofuran and butyrolactone lignans with antioxidant activity from the stem bark of Styrax japonica.

A new furofuran lignan, styraxlignolide B (1), and four new dibenzyl-gamma-butyrolactone lignans, styraxlignolides C-F (2-5), were isolated from the EtOAc-soluble fraction of stem bark of Styrax japonica. Known compounds, taraxerol (6), syringin (7), and (-)-pinoresinol glucoside (8), were also obtained. The structures of styraxligonolides B-F were determined as 2alpha-(4'-hydroxy-3'-methoxyphenyl)-6alpha-(3' ',4' '-methylenedioxyphenyl)-8-oxo-3,7-dioxabicyclo[3.3.0]octane 4'-O-(beta-D-glucopyranoside) (1), (2S,3S)-2alpha-(3' '-hydroxy-4' '-methoxybenzyl)-3beta-(4'-hydroxy-3'-methoxybenzyl)-gamma-butyrolactone 4'-O-(beta-D-glucopyranoside) (2), (2S,3S)-2alpha-(4' '-hydroxy-3' '-methoxybenzyl)-3beta-(4'-hydroxy-3'-methoxybenzyl)-gamma-butyrolactone 4'-O-(beta-D-glucopyranoside) (3), (2S,3S)-2alpha-(4' '-hydroxy-3' '-methoxybenzyl)-3beta-(4'-hydroxy-3'-methoxybenzyl)-gamma-butyrolactone 4' '-O-(beta-D-glucopyranoside) (4), and (2S,3S)-2alpha-(3' ',4' '-dimethoxybenzyl)-3beta-(4'-hydroxy-3'-methoxybenzyl)-gamma-butyrolactone 4'-O-(beta-D-glucopyranoside) (5) by spectroscopic means including 2D NMR. Compounds 1-8 were tested in vitro for antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Styraxlignolide C (2), styraxlignolide D (3), styraxlignolide E (4), and (-)-pinoresinol glucoside (8) exhibited weak radical-scavenging activity in the DPPH assay, with IC50 values of 380, 278, 194, and 260 microM, respectively.

4-Butyrolactone↗

Furo-1,2-naphthoquinones from Crataegus pinnatifida with ICAM-1 expression inhibition activity.

Two new furo-1,2-naphthoquinones, crataequinones A (1) and B (2), were isolated from the fruits of Crataegus pinnatifida. The structures of two new compounds were determined as 11,12-dimethoxy-3,4-furo-1,2-naphthoquinone (1) and 11,12-dimethoxy-5-hydroxy-3,4-furo-1,2-naphthoquinone (2) by spectroscopic analysis. The two compounds 1 and 2 showed significant inhibitory activity with IC50 values of 33 and 90 microM, respectively, against the expression of intercellular adhesion molecule-1 (ICAM-1).

Animals↗

Anti-complement activity of norlignans and terpenes from the stem bark of Styrax japonica.

A new norlignan, styraxlignolide A (1), and two new terpenes, styraxosides A (2) and B (3), were isolated from the MeOH-soluble fraction of Styrax japonica Sieb. et Zucc. (Styracaceae) stem bark, together with two known compounds, egonol (4) and masutakeside I (5). The new compounds were determined as 5-(3''-hydroxypropyl)-7-methoxy-2-(3',4'-dimethoxyphenyl)-benzofuran 3''- O-[beta-D-xylopyranoside-(1-->6)-beta- D-glucopyranoside] (1), 3beta,7beta-dihydroxy-4alpha,4beta,8beta,10beta,14alpha-pentamethyl-5alpha-gon-16-en-2-one 3-O-[beta-D-glucopyranoside-(1-->2)-beta-D-glucopyranoside] (2), and 3beta,17beta-dihydroxy-28-norolean-12-en-16-one 3-O-[alpha-L-rhamopyranoside-(1-->2)-beta-D-glucuronopyranoside] (3) by spectroscopic means including 2D-NMR. The five compounds were tested in vitro for anti-complement activity against the complement system. Compounds 1, 3, 4, and 5 displayed inhibitory activity in the anti-complement assay, with IC50 values of 123, 65, 33, and 166 microM, respectively. Compound 1a and camellenodiol (3a), obtained from acid hydrolysis of 1 and 3, respectively, did not affect the hemolytic activity of human serum against sensitized erythrocytes. This shows that a sugar seems to play a role of enhancing significantly anti-complement activity.

Complement System Proteins↗

Increase of caspase-3 activity by lignans from Machilus thunbergii in HL-60 cells.

Nine lignans and two butanolides were isolated from the stem bark of Machilus thunbergii and their structures were identified as machilin A (1), licarin B (2), zuonin B (3), macelignan (4), secoisolancifolide (5), isolancifolide (6), oleiferin C (7), meso-dihydroguaiaretic acid (8), licarin A (9), machilin F (10), and nectandrin B (11) by spectroscopic means. These compounds were assessed for their abilities to activate a caspase-3 activity in human promyeloid leukemic HL-60 cells. The intracellular caspase-3 activity of macelignan (4), oleiferin C (7), meso-dihydroguaiaretic acid (8), and licarin A (9) increased approximately 3.04, 6.16, 2.10, and 3.10-fold at 100 microM over that of untreated control. In addition, compounds 4, 7, 8, and 9 induced internucleosomal DNA fragmentation in HL-60 cells.

4-Butyrolactone↗

Wogonin inhibits ischemic brain injury in a rat model of permanent middle cerebral artery occlusion.

The present study evaluated the effect of wogonin, a flavonoid originated from the root of Scutellaria baicalensis GEORGI, on focal ischemic brain injury in rats. Focal brain ischemia was induced by the permanent occlusion of middle cerebral artery (pMCAO) for 24 h with a silicone rubber cylinder inserted through the right internal carotid artery. We found that wogonin, intraperitoneally administered at a dosage of 20 mg/kg at 30 min before and 4 h after the surgery, reduced the pMCAO-induced infarct areas in the cerebral cortex as well as in the striatum. The total volume of infarction was significantly reduced by the treatment with wogonin. In addition, wogonin was found to significantly improve the pMCAO-induced behavioral deficits at 24 h after the surgery. Taken together, these results demonstrate that wogonin inhibits ischemic brain injury and improves behavioral dysfunction caused by pMCAO. These findings, along with previous reports demonstrating the neuroprotective effects of wogonin, provide strong pharmacological basis for the use of wogonin or Scutellaria baicalensis in the treatment of stroke.

Animals↗

Anti-complementary activity of triterpenoides from fruits of Zizyphus jujuba.

In order to determine on the anti-complement activity of triterpenes, following eleven triterpenoides were isolated from the fruits of the Zizyphus jujuba MILL: ceanothane-type triterpenes: colubrinic acid (1), zizyberenalic acid (11); lupane-type triterpenes: alphitolic acid (2), 3-O-cis-p-coumaroyl alphitolic acid (3), 3-O-trans-p-coumaroyl alphitolic acid (4), betulinic acid (7), betulonic acid (9); and oleanane-type triterpenes: 3-O-cis-p-coumaroyl maslinic acid (5), 3-O-trans-p-coumaroyl maslinic acid (6), oleanolic acid (8), oleanonic acid (10). These compounds were examined for their anti-complement activity against the classical pathway of the complement system. Among them, compounds 5, 6, and 8 exhibited significant anti-complement activity with IC(50) values of 101.4, 143.9, and 163.4 microM, respectively, whereas the ceanothane-type and the lupane-type triterpenes were inactive. This suggests that the oleanane-structure plays an important role in inhibiting the hemolytic activity of human serum against erythrocytes.

Chromatography, High Pressure Liquid↗