Publications (13)28.21 Total impact
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Article: Selective apoptosis in hepatic stellate cells mediates the antifibrotic effect of phenanthrenes from Dendrobium nobile.
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ABSTRACT: Regardless of the etiology, cellular death of the liver parenchymal hepatocyte seems to be a primary event of hepatic fibrogenesis, which ultimately results in hepatic stellate cell (HSC) activation and the synthesis of extracellular matrix proteins. Recently it has been demonstrated that hepatic fibrosis can be a reversible process when the stimulus is properly eliminated. Apoptotic removal of active HSC is considered an essential part of the resolution. By employing the HSC cell line, HSC-T6, it was found that the methanol extract of Dendrobium nobile stem significantly inhibited the proliferation of HSC-T6 cells. Three phenanthrenes, denbinobin, fimbriol B and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene isolated from D. nobile were proven to inhibit HSC proliferation. Growth arrest of HSCs by these compounds was accompanied by cellular loss via autophagy-linked apoptosis. The maximal dose of these compounds, however, had little effect on primary cultured hepatocytes in rats. Collagen deposition in HSC-T6 cells was attenuated by these phenanthrenes. Collectively, the above results demonstrated that denbinobin, fimbriol B and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene exhibited antifibrotic activities possibly by the induction of selective cell death in HSCs but not in hepatocytes, implying that these compounds may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis.Phytotherapy Research 12/2011; 26(7):974-80. · 2.09 Impact Factor -
Article: Inhibitory alkaloids from Dictamnus dasycarpus root barks on lipopolysaccharide-induced nitric oxide production in BV2 cells.
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ABSTRACT: The methanolic extract of Dictamnus dasycarpus root barks afforded one new glycosidic quinoline alkaloid, 3-[1β-hydroxy-2-(β-D-glucopyranosyloxy)-ethyl)-4-methoxy-2(1H)-quinolinone (1), together with nine known compounds, preskimmianine (2), 8-methoxy-N-methylflindersine (3), dictamine (4), γ-fagarine (5), halopine (6), skimmianine (7), dictangustine-A (8), iso-γ-fagarine (9), isomaculosidine (10). The isolated alkaloids significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV2 cells. Among them, compounds 3 and 7 showed the most potent inhibitory activities on LPS-induced NO production.Journal of Enzyme Inhibition and Medicinal Chemistry 08/2011; 27(4):490-4. · 1.62 Impact Factor -
Article: Luteolin downregulates IL-1β-induced MMP-9 and -13 expressions in osteoblasts via inhibition of ERK signalling pathway.
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ABSTRACT: The inhibitory effect of four structurally related flavonoids, apigenin, baicalein, luteolin and quercetin on the matrix metalloproteinase (MMP)-9 and -13 expressions in osteoblasts was investigated. Treatment with IL-1β induced both MMP-9 and -13 mRNA expressions as measured by quantitative real-time PCR. Luteolin and apigenin decreased IL-1β-induced MMP-9 and -13 mRNA expressions, whereas baicalein and quercetin showed little effects. Related to signalling, treatment with IL-1β induced ERK phosphorylation as measured by Western blotting. Further studies showed that transfection with a constitutively active form of the Ras protein (Ras(V12)) induced stronger ERK phosphorylation and upregulated MMP-9 and -13 mRNA expressions. However, transfection with a dominant-negative form of the Ras protein (Ras(N17)) inhibited the ERK activation and MMP-9 and -13 mRNA expressions induced by IL-1β, which supported the involvement of ERK signalling in IL-1β-induced MMP-9 and -13 expressions. Treatment with luteolin effectively inhibited the IL-1β-induced ERK activation in dose-dependent manner. Taken together, luteolin might inhibit IL-1β-induced MMP-9 and -13 expressions, in part, via inhibition of ERK signalling.Journal of Enzyme Inhibition and Medicinal Chemistry 06/2011; 27(2):261-6. · 1.62 Impact Factor -
Article: Limonoids from Dictamnus dasycarpus protect against glutamate-induced toxicity in primary cultured rat cortical cells.
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ABSTRACT: In our previous report, four limonoids, obacunone, limonin, fraxinellone, and calodendrolide, isolated from Dictamnus dasycarpus showed significant neuroprotective activity against glutamate toxicity in primary cultured rat cortical cells. This study investigated neuroprotective mechanism of these compounds using the same in vitro culture system. These four compounds showed significant neuroprotective activity at the concentration of 0.1 muM. They effectively inhibited calcium influx and overproduction of cellular nitric oxide and reactive oxygen species accompanied by glutamate-induced neurotoxicity. In addition, these compounds significantly preserved mitochondrial membrane potential and activities of antioxidative enzymes. Our results showed that obacunone, limonin, fraxinellone, and calodendrolide significantly protect primary culture cortical cells against glutamate-induced toxicity by preserving the antioxidant defense system. These compounds might offer potential drug development candidate for various neurodegenerative diseases involved with glutamate.Journal of Molecular Neuroscience 02/2010; 42(1):9-16. · 2.50 Impact Factor -
Article: Asiatic acid derivatives protect primary cultures of rat hepatocytes against carbon tetrachloride-induced injury via the cellular antioxidant system.
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ABSTRACT: We attempted to elucidate the hepatoprotective mechanism of two asiatic acid (AS) derivatives, 3beta,23-dihydroxyurs-2-oxo-12-ene-28-oic acid (AS-10) and 3beta,23-dihydroxyurs-12-ene-28-oic acid (AS-14), which exhibited significant protective activity against carbon tetrachloride (CCl4)-induced hepatotoxicity in primary cultures of rat hepatocytes. Our findings showed that AS-10 and AS-14 preserved the level of glutathione and the activities of antioxidant enzymes such as glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. In addition, these compounds ameliorated lipid peroxidation, as demonstrated by a reduction in the production of malondialdehyde. Furthermore, AS-10 and AS-14 did not restore the reduced total GSH level by BSO, indicating that the hepatoprotective activities of these compounds may be involved, in part, by regulating GSH synthesis. From these results, we suggest that both AS-10 and AS-14 exerted their hepatoprotective activities against CCl4-induced injury by preserving the cellular antioxidative defense system.Natural product communications 07/2009; 4(6):765-8. · 1.24 Impact Factor -
Article: Stimulatory constituents of Eclipta prostrata on mouse osteoblast differentiation.
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ABSTRACT: One flavonoid, diosmetin (1), and two isoflavonoids, 3'-hydroxybiochanin A (2) and 3'-O-methylorobol (3), were isolated from the methanol extract of Eclipta prostrata L. by a bioactivity-guided fractionation technique using primary cultures of mouse osteoblasts as an in vitro assay system. All three compounds significantly increased osteoblast differentiation as assessed by the alkaline phosphatase activity..Phytotherapy Research 09/2008; 23(1):129-31. · 2.09 Impact Factor -
Article: Antifibrotic activity of diterpenes from Biota orientalis leaves on hepatic stellate cells.
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ABSTRACT: Antifibrotic effect of twelve diterpenes (1-12) from the 90% methanolic fraction of Biota orientalis leaves was evaluated employing HSC-T6 cells by assessing cell proliferation and morphological change. Among these diterpenes, totarol (8) and isopimara-8(14),15-dien-19-oic acid (9) dramatically reduced cell proliferation in dose-and time-dependent manner. Furthermore, treatment with these compounds resulted in the different pattern of morphological changes of HSC-T6 cells. Taken together, antiproliferative activity of diterpenes from B. orientalis might suggest therapeutic potentials against liver fibrosis.Archives of Pharmacal Research 08/2008; 31(7):866-71. · 1.59 Impact Factor -
Article: Antifibrotic phenanthrenes of Dendrobium nobile stems.
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ABSTRACT: Two new phenanthrenes ( 1 and 6) and four new dihydrophenanthrenes ( 2- 5) were isolated from a methanolic extract of Dendrobium nobile stems, along with 13 known phenanthrenes and dihydrophenanthrenes ( 7- 19). By spectroscopic analysis, the structures of compounds 1- 6 were determined as 2,8-dihydroxy-3,4,7-trimethoxyphenanthrene ( 1), 3-hydroxy-2,4,7-trimethoxy-9,10-dihydrophenanthrene ( 2), 2,8-dihydroxy-3,4,7-trimethoxy-9,10-dihydrophenanthrene ( 3), 2-hydroxy-4,7-dimethoxy-9,10-dihydrophenanthrene ( 4), 2,2'-dihydroxy-3,3',4,4',7,7'-hexamethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene ( 5), and 2,3,5-trihydroxy-4,9-dimethoxyphenanthrene ( 6), respectively. Antifibrotic activity of compounds 1- 19 was evaluated employing HSC-T6, an immortalized rat hepatic stellate cell line, as an in vitro assay system by assessing cell proliferation.Journal of Natural Products 01/2008; 70(12):1925-9. · 3.13 Impact Factor -
Article: Antiproliferative activity of triterpenoids from Eclipta prostrata on hepatic stellate cells.
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ABSTRACT: Hepatic stellate cells (HSCs) have been known to play a key role in the pathogenesis of liver fibrosis. In the course of screening antifibrotic activity of natural products employing HSC-T6, a rat hepatic stellate cell line as an in vitro assay system, the methanolic extract of aerial parts of Eclipta prostrata L. showed significant inhibitory activity on HSCs proliferation. Activity-guided fractionation led to the isolation of five oleanane-type triterpenoids, echinocystic acid (1), eclalbasaponin II (2), eclalbasaponin V (3), eclalbasaponin I (4) and eclalbasaponin III (5), which are all echinocystic acid derivatives. Among the five echinocystic acid derivatives isolated, echinocystic acid (1) and eclalbasaponin II (2) significantly inhibited the proliferation of HSCs in dose- and time-dependent manners. Our present study also suggests the importance of free carboxylic acid at C-28 position in echinocystic acid derivatives for the antifibrotic activity. Taken together, antifibrotic activity of E. prostrata and its triterpenoids might suggest the therapeutic potentials against liver fibrosis.Phytomedicine: international journal of phytotherapy and phytopharmacology 12/2007; 15(9):775-80. · 2.17 Impact Factor -
Article: Stimulatory activity of lignans from Machilus thunbergii on osteoblast differentiation.
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ABSTRACT: Phytoestrogens are naturally occurring compounds exerting estrogenic activity, and include isoflavonoids, flavonoids and lignans. In the present study, we evaluated the stimulating activity of six lignans, meso-dihydroguaiaretic acid, nordihydroguaiaretic acid, machilin A, guaiacin, isoguaiacin and isoguaiacin dimethylether, from Machilus thunbergii, on osteoblast differentiation employing primary cultures of mouse osteoblast as an in vitro assay system. Among the six lignans tested, arylnaphthalene type lignans such as guaiacin, isoguaiacin and isoguaiacin dimethylether significantly increased alkaline phosphatase activity, whereas bibenzylbutane type lignans such as meso-dihydroguaiaretic acid, nordihydroguaiaretic acid and machilin A showed little effects. Isoguaiacin and isoguaiacin dimethylether also increased collagen synthesis as well as calcium deposition. In addition, treatment of the mouse osteoblasts with tamoxifen markedly reduced ALP activity increased by isoguaiacin or isoguaiacin dimethylether, suggesting the involvement of estrogen receptor in the action of these lignans on osteoblast differentiation. Taken together, these results suggest that arylnaphthalene type lignans such as guaiacin, isoguaiacin and isoguaiacin dimethylether significantly increase osteoblast differentiation.Biological & Pharmaceutical Bulletin 05/2007; 30(4):814-7. · 1.66 Impact Factor -
Article: Osteoblast differentiation stimulating activity of biflavonoids from Cephalotaxus koreana.
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ABSTRACT: Six amentoflavone-type biflavonoids, bilobetin (1), ginkgetin (2), 4',7''-di-O-methyl-amentoflavone (3), 7-O-methyl-isoginkgetin (4), sciadopitysin (5), and 7,4',7'',4'''-O-methyl-amentoflavone (6), were isolated from the EtOAc fraction of Cephalotaxus koreana Nakai (Cephalotaxaceae) by bioactivity-guided fractionation technique using primary cultures of mouse osteoblasts as an in vitro assay system. Among the six biflavonoids isolated, bilobetin (1), sciadopitysin (5), and 7,4',7'',4'''-O-methyl-amentoflavone (6) significantly increased osteoblast differentiation as assessed by alkaline phosphatase activity, collagen synthesis, and mineralization. Considering structure-activity relationship, methoxyl groups at 4' and 4''' in the B rings in amentoflavone-type biflavonoid might be important in osteoblast differentiation. Taken together, our present study suggests therapeutic potential of biflavonoids against bone diseases such as osteoporosis.Bioorganic & Medicinal Chemistry Letters 07/2006; 16(11):2850-4. · 2.55 Impact Factor -
Article: Protective activities of stilbene glycosides from Acer mono leaves against H2O2-induced oxidative damage in primary cultured rat hepatocytes.
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ABSTRACT: In our previous study, we isolated two new hepatoprotective stilbene glycosides, 5-O-methyl-(E)-resveratrol 3-O-beta-D-glucopyranoside (MRA) and 5-O-methyl-(E)-resveratrol 3-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (MRAG), from the methanolic extract of Acer mono leaves. Thereby, we have attempted to elucidate the hepatoprotective mechanism of these compounds, focusing on antioxidative effects, using hydrogen peroxide (H2O2)-injured primary cultures of rat hepatocytes. Both MRA and MRAG showed potent hepatoprotective activities in pretreatment but showed little effects in posttreatment. In addition, they increased the glutathione (GSH) level in the normal control cultures and significantly prevented the depletion of GSH in H2O2-injured primary cultured rat hepatocytes. Moreover, these compounds significantly restored the level of GSH depleted by buthionine sulfoximine or diethylmaleate in the presence or absence of H2O2. Furthermore, these compounds preserved the activities of antioxidant enzymes such as superoxide dismutase, glutathione reductase, and glutathione peroxidase reduced by H2O2 insults. Meanwhile, MRA and MRAG showed moderate scavenging effects with IC50 values of 103.6 and 80.5 microM, respectively, as determined by 1,1-diphenyl-2-picryl-hydrazyl free radical scavenging activity. Taken together, these results suggest that MRG and MRAG exert significant hepatoprotective activities against H2O2-induced hepatotoxicity by maintaining the antioxidative defense system rather than scavenging free radicals.Journal of Agricultural and Food Chemistry 06/2005; 53(10):4182-6. · 2.82 Impact Factor -
Article: Two new hepatoprotective stilbene glycosides from Acer mono leaves.
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ABSTRACT: Two new stilbene glycosides, 5-O-methyl-(E)-resveratrol 3-O-beta-d-glucopyranoside (1) and 5-O-methyl-(E)-resveratrol 3-O-beta-D-apiofuranosyl-(1-->6)-beta-d-glucopyranoside (2), were isolated from the leaves of Acer mono, along with seven known compounds. Among these compounds, 1, 2, and quercetin (3) showed significant hepatoprotective activities against H(2)O(2)-induced toxicity in primary cultures of rat hepatocytes.Journal of Natural Products 02/2005; 68(1):101-3. · 3.13 Impact Factor
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Institutions
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2005–2011
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Seoul National University
- Research Institute of Pharmaceutical Sciences
Seoul, Seoul, South Korea
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