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Biomedical subjects

Sam Sik Kang

Publications and source records attributed to Sam Sik Kang.

At least 37 records · Page 2Linked to original sources

Inhibitory effects of furoquinoline alkaloids from Melicope confusa and Dictamnus albus against human phosphodiesterase 5 (hPDE5A) in vitro.

Eight furoquinoline alkaloids were purified from two plants belonging to the Rutaceae family. Kokusaginine, skimmianine, evolitrine, and confusameline were purified from Melicope confusa, and haplopine, robustine, dictamine, and gamma-fagarine from Dictamnus albus. In this study, the eight furoquinoline alkaloids were examined for inhibitory potency against human phosphodiesterase 5 (hPDE5A) in vitro. DNA encoding the catalytic domain of human PDE5A was amplified from the mRNA of T24 cells by RT-PCR and was fused to GST in an expression vector. GST-tagged PDE5A was then purified by glutathione affinity chromatography and used in inhibition assays. Of the eight alkaloids, gamma-fagarine was the most potent inhibitor of PDE5A, and its single methoxy group at the C-8 position was shown to be critical for inhibitory activity. These results clearly illustrate the relationship between PDE5A inhibition and the methoxy group position in furoquinoline alkaloids.

3',5'-Cyclic-GMP Phosphodiesterases↗

A phenolic glucoside isolated from Prunus serrulata var. spontanea and its peroxynitrite scavenging activity.

A new phenolic glucoside (1), pursargentoside, was isolated from the leaves of Prunus serrulata var. spontanea, along with three other known compounds, orobol 7-omicron-glucoside (2), 1beta, 2alpha, 3alpha, 24-tetrahydroxy-urs-12-en-28-oic acid (3), and chlorogenic acid (4). The structure of pursargentoside (1) was identified by spectroscopic data analysis including 1D and 2D NMR spectroscopy, as 2-omicron-beta-(6'-benzoyl)-glucopyranosyl omicron-(Z)-coumaric acid. Compounds 1, 2, and 4 exhibited ONOO scavenging activity, whereas compound 3 was determined to be virtually inactive.

Free Radical Scavengers↗

Antioxidant activity of anthraquinones and flavonoids from flower of Reynoutria sachalinensis.

Bioassay-guided fractionation of methanol extract of Reynoutria sachalinensis flower using DPPH assay has led to the isolation of three anthraquinones and three flavonoids. Their structures were identified as emodin (1), emodin-8-O-beta-D-glucopyranoside (2), physcion-8-O-beta-D-glucopyranoside (3), quercetin-3-O-alpha-L-arabinofuranoside (4), quercetin-3-O-beta-D-galactopyranoside (5), and quercetin-3-O-beta-D-glucuronopyranoside (6) by comparing their physicochemical and spectral data with those published in literatures. All isolated compounds were evaluated for antioxidant activities with free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging, superoxide radical scavenging and Cu2+-mediated low density lipoprotein (LDL) oxidation assay. The results demonstrated that three flavonoids, 4, 5, and 6 had remarkable antioxidant activities with the IC50 values of 64.3, 54.7, and 46.2 microM (DPPH scavenging), the IC50 values of 6.0, 6.7, and 4.4 microM (superoxide radical scavenging) and the IC50 values of 3.8, 3.2, and 5.4 microM against LDL oxidation, respectively.

Anthraquinones↗

Inhibitory constituents against cyclooxygenases from Aralia cordata Thunb.

Seven diterpenes, four polyacetylenes, a lipid glycerol, and two sterols were isolated from the methylene chloride fraction of the root of Aralia cordata. Their chemical structures were determined as (-)-pimara-8(14),15-dien-19-oic acid (2), pimaric acid (3), (-)-kaur-16-en-19-oic acid (4), 17-hydroxy-ent-kaur-15-en-19-oic acid (9), 7alpha-hydroxy-(-)-pimara-8(14),15-dien-19-oic acid (10), 16alpha,17-dihydroxy-(-)-kauran-19-oic acid (11), 16-hydroxy-17-isovaleroyloxy-ent-kauran-19-oic acid (12), falcarindiol (5), dehydrofalcarindiol (6), dehydrofalcarindiol-8-acetate (7), falcarindiol-8-acetate (8), alpha-mono palmitin (13), stigmasterol (1), and daucosterol (14) by the spectral evidences. These compounds were tested with COX-1 and COX-2 inhibition assays. This study found that compounds 2, 4, 5, 6, 7, 8, and 10 inhibited COX-1 dependent conversion of the exogenous arachidonic acid to PGE2 in a dose-dependent manner with IC50 values of 134.2 microM, 121.6 microM, 170 microM, 50.4 microM, 11.7 microM, 99.6 microM, and 69.6 microM, respectively. But, most of these compounds weakly inhibited COX-2 dependent PGE2 generation. Among them, only compound 4 showed relatively significant inhibitory activity (IC50: 127.6 microM).

Aralia↗

New anti-inflammatory formulation containing Synurus deltoides extract.

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1% inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7-day model of multiple treatment of TPA (38.1% inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin E2 production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

Acetic Acid↗

Anti-estrogenic activity of lignans from Acanthopanax chiisanensis root.

Anti-estrogenic activity of (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), and 3-(3,4-dimethoxybenzyl)-2-(3,4-methylenedioxybenzyl)butyrolactone (5) isolated from the root of Acanthopanax chiisanensis was tested using Ishikawa cells. Among them, compound 3 exhibited anti-estrogenic activity (IC50 = 4.86 microM).

Adenosine Triphosphatases↗

In vitro free radical and ONOO- scavengers from Sophora flavescens.

Activity-guided fractionation of the CH2Cl2-soluble fraction of the roots of Sophora flavescens furnished five 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavengers: trans-hexadecyl ferulic acid (1), cis-octadecyl ferulic acid (2), trans-hexadecyl sinapic acid (3), (-)-4-hydroxy-3-methoxy-(6aR,11aR)-8,9-methylenedioxypterocarpan (4) and desmethylanhydroicaritin (8), along with nine known inactive compounds: (-)-maackiain (5), xanthohumol (6), formononetin (7), (2S)-2'-methoxykurarinone (9), (2S)-3beta,7,4'-trihydroxy-5-methoxy-8-(gamma,gamma-dimethylallyl)-flavanone (10), (2S)-7,4'-dihydroxy-5-methoxy-8-(gamma,gamma-dimethylallyl)-flavanone (11), umbelliferone (12), kuraridin (13), and trifolirhizin (14). Compounds 1-4 and 8 exhibited DPPH free radical scavenging effects at IC50 values of 33.01 +/- 0.20, 57.06 +/- 0.16, 39.84 +/- 0.36, 35.83 +/- 0.47, and 18.11 +/- 0.04 microM, respectively. L-Ascorbic acid, when used as a positive control, exhibited an IC50 value of 7.39 +/- 0.01 microM. Compounds 1-4 and 8 also appeared to exert significant scavenging effects on authentic ONOO-, with IC50 values of 5.76 +/- 1.19, 15.06 +/- 1.64, 8.17 +/- 4.97, 1.95 +/- 0.29, and 4.06 +/- 2.41 microM, respectively. Penicillamine (IC50 = 2.36 +/- 0.79 microM) was used as a positive control. In addition, compounds 2, 4, 6, 8, and 10 were isolated from this plant for the first time.

Free Radical Scavengers↗

Norditerpenoid alkaloids and other components from the processed tubers of Aconitum carmichaeli.

A new norditerpenoid and a known alkaloid were isolated from the alkaloidal fraction of the processed tubers of Aconitum carmichaeli. The structure of the new norditerpenoid alkaloid was elucidated as lipoforesaconitine (1) on the basis of spectroscopic analysis. The known norditerpenoid alkaloid was characterized as lipoyunanaconitine (2). In addition, a new flavonoid, 6"-O-acetylliquiritin (7), along with a known ceramide, (2S,3S,4R,8E)-2-[(2'R)-2'-hydroxylignoceroylamino]-8(E)-octadecene-1,3,4-triol (3), as well as a known steroid saponin, gracillin (8), and three known flavonoids, liquiritigenin (4), isoliquiritigenin (5), and liquiritin (6), were also isolated and characterized. All known compounds were isolated from this plant for the first time. The structures of the isolates were established by spectroscopic and chemical methods.

Acetylation↗

Aldose reductase inhibitors from the fruiting bodies of Ganoderma applanatum.

The isolation and characterization of rat lens aldose reductase (RLAR) inhibitors from the fruiting bodies of Ganoderma applanatum were conducted. Among the extracts and fractions from G. applanatum tested, the MeOH extract and EtOAc fraction were found to exhibit potent RLAR inhibition in vitro, their IC50 being 1.7 and 0.8 microg/ml, respectively. From the active EtOAc fraction, seven compounds with diverse structural moieties were isolated and identified as D-mannitol (1), 2-methoxyfatty acids (2), cerebrosides (3), daucosterol (4), 2,5-dihydroxyacetophenone (5), 2,5-dihydroxybenzoic acid (6), and protocatechualdehyde (7). Among them, protocatechualdehyde (7) was found to be the most potent RLAR inhibitor (IC50=0.7 microg/ml), and may be useful for the prevention and/or treatment of diabetic complications.

Aldehyde Reductase↗

Ginkgetin, a Biflavone from Ginko biloba leaves, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells.

Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A(2) inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D(2) (PGD(2)) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC(50) values of 0.75 microM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD(2) product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C(4) (LTC(4)) in a dose dependent manner, with an IC(50) value of 0.33 microM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC(50) value of 6.52 microM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.

Animals↗

Antiinflammatory activity of astilbic acid from Astilbe chinensis.

This study examined the effect of astilbic acid (3beta,6beta-dihydroxyolean-12-en-27-oic acid), which is a herbal medicine isolated from Astilbe chinensis. Astilbic acid inhibited 5-lipoxygenase (5-LOX)-dependent leukotriene C4 (LTC4) generation in bone marrow-derived mast cells in a concentration-dependent manner with an IC50 value of 2.1 microM. In addition, astilbic acid was tested in a rat passive cutaneous anaphylaxis (PCA) reaction assay by administering 10 to 50 mg/kg i.p. Astilbic acid dose dependently inhibited the PCA reaction, which was activated by anti-dinitrophenyl (DNP) IgE. Furthermore, this compound inhibited mouse acetic acid-induced writhing (47-62% inhibition at 0.4-50 mg/kg) after being administered orally, while aspirin (200 mg/kg) showed 62% inhibition. These results suggest that astilbic acid may be beneficial in regulating various inflammatory processes.

Animals↗

Araloside A, an antiulcer constituent from the root bark of Aralia elata.

Araloside A, a potent inhibitor of gastric lesion and ulcer formation in rats, was isolated from the root bark of Aralia elata through a bioassay-guided separation procedure. The compound exhibited significant reduction of HCl.ethanol-induced gastric lesions and aspirin-induced gastric ulcers at oral doses of 50 and 100 mg/kg, respectively. These activities are comparable to those of cimetidine.

Animals↗

Biflavone glucosides from Ginkgo biloba yellow leaves.

Phytochemical investigation of Ginkgo biloba (Ginkgoaceae) has resulted in the isolation of two new biflavone glucosides, ginkgetin 7''-O-beta-D-glucopyranoside (1) and isoginkgetin 7-O-beta-D-glucopyranoside (2). The structures were determined on the basis of chemical and spectroscopic evidences.

Chromatography, Thin Layer↗

Saponins and other constituents from the leaves of Aralia elata.

A new triterpenoid saponin, together with five known saponins, were isolated from the nonpolar n-hexane fraction of the leaves of Aralia elata. The structure of the new saponin, durupcoside C, was elucidated as hederagenin 3-O-beta-D-glucopyranosyl(1-->3)-beta-D-glucopyranosyl(1-->3)-alpha-L-arabinopyranoside on the basis of spectroscopic analysis. The known saponins were characterized as 3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranosyl hederagenin 28-O-beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl ester, hederagenin 3-O-beta-D-glucopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranoside, oleanolic acid 3-O-beta-D-glucopyranosyl(1-->3)-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranoside, hederagenin 3-O-alpha-L-rhamnopyranosyl(1-->2)-alpha-L-arabinopyranoside (alpha-hederin), and hederagenin 3-O-beta-D-glucopyranosyl(1-->3)-alpha-L-arabinopyranoside (collinsonidin). In addition, two known lipids, Arisaema glyceride 3 and ceramide mixtures were also isolated and characterized. Collinsonidin and two known lipids were isolated for the first time from this plant.

Aralia↗

Humulene derivatives from Zingiber zerumbet with the inhibitory effects on lipopolysaccharide-induced nitric oxide production.

A new humulene sesquiterpene, 5-hydroxyzerumbone (5-hydroxy-2E,6E,9E-humulatrien-8-one) (1) and a known compound, zerumboneoxide (2) were isolated from the rhizomes of Zingiber zerumbet (Zingiberaceae), and found to inhibit lipopolysaccharide-induced nitric oxide production in murine macrophage RAW 264.7 cells with IC50 values of 14.1 and 23.5 microM, respectively, by bioassay-guided fractionation (positive control: N(omega)-monomethyl-L-arginine, IC50=21.3 microM). The structure of 1 was determined by spectroscopic methods including 1D and 2D-NMR.

Animals↗

Anti-inflammatory plant flavonoids and cellular action mechanisms.

Plant flavonoids show anti-inflammatory activity in vitro and in vivo. Although not fully understood, several action mechanisms are proposed to explain in vivo anti-inflammatory action. One of the important mechanisms is an inhibition of eicosanoid generating enzymes including phospholipase A2, cyclooxygenases, and lipoxygenases, thereby reducing the concentrations of prostanoids and leukotrienes. Recent studies have also shown that certain flavonoids, especially flavone derivatives, express their anti-inflammatory activity at least in part by modulation of proinflammatory gene expression such as cyclooxygenase-2, inducible nitric oxide synthase, and several pivotal cytokines. Due to these unique action mechanisms and significant in vivo activity, flavonoids are considered to be reasonable candidates for new anti-inflammatory drugs. To clearly establish the therapeutic value in inflammatory disorders, in vivo anti-inflammatory activity, and action mechanism of varieties of flavonoids need to be further elucidated. This review summarizes the effect of flavonoids on eicosanoid and nitric oxide generating enzymes and the effect on expression of proinflammatory genes. In vivo anti-inflammatory activity is also discussed. As natural modulators of proinflammatory gene expression, certain flavonoids have a potential for new anti-inflammatory agents.

Animals↗

Neuroprotective effects of flavones on hydrogen peroxide-induced apoptosis in SH-SY5Y neuroblostoma cells.

Neuroprotective effects of flavones were examined. Luteolin and apigenin exhibited neuroprotection against oxidative stress-induced cell death in SH-SY5Y cells. Free radical scavenging activity and neuroprotection assays revealed that flavones exerted their neuroprotective effects via the direct interaction with the apoptotic caspase pathway independently of their antioxidant activity.

Apoptosis↗