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Biomedical subjects

Sang Hoon Jung

Publications and source records attributed to Sang Hoon Jung.

At least 19 recordsLinked to original sources

Inhibition of lipopolysaccharide-induced iNOS and COX-2 expression by dehydroevodiamine through suppression of NF-kappaB activation in RAW 264.7 macrophages.

Dehydroevodiamine is a major bioactive quinazoline alkaloid isolated from Evodiae Fructus. We investigated the anti-inflammatory properties of dehydroevodiamine in RAW 264.7 murine macrophages. The results indicated that dehydroevodiamine inhibited the expression of LPS-induced iNOS and COX-2 proteins and suppressed also their mRNAs from RT-PCR experiment on RAW 264.7 cells. Furthermore, this compound inhibited the level of LPS-stimulated prostaglandin E2 (PGE2) and LPS-induced nuclear factor-kappa B (NF-kappaB). Therefore, we suggested that the effect of dehydroevodiamine-mediated inhibition of the expression LPS-induced iNOS and COX-2 genes is due to under the suppression of NF-kappaB activation in the transcriptional level.

Alkaloids↗

Anti-angiogenic and anti-tumor activities of 2'-hydroxy-4'-methoxychalcone.

In the present study, we evaluated the in vitro and in vivo anti-angiogenic and anti-tumor activities of 2'-hydroxy-4'-methoxychalcone (HMC). HMC decreased angiogenesis in both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor (bFGF)-induced vessel formation in the mouse Matrigel plug assay. This compound also reduced the proliferation of calf pulmonary arterial endothelial cells and was found to possess relatively weak gelatinase/collagenase inhibitory activity in vitro. HMC, when administered subcutaneously at the dose of 30 mg/kg for 20 d to mice implanted with murine Lewis lung carcinoma, caused a significant inhibition of tumor volume by 27.2%. Intraperitoneal (i.p.) treatment at the same dosage for 10 d to ICR mice bearing sarcoma 180 caused a significant suppression in tumor weight by 33.7%. Taken together, out data demonstrate that the anti-angiogenic activities of HMC might be due to anti-proliferative activity under inhibition of the induction of COX-2 enzyme. Furthermore, the results suggest that the potent anti-angiogenic activity of HMC seems to be the possible mechanism of action in these animal models of solid tumors.

Angiogenesis Inhibitors↗

Synthesis and PPAR-gamma ligand-binding activity of the new series of 2'-hydroxychalcone and thiazolidinedione derivatives.

Fifteen chalcones and three thiazolidinedione (TZD) chalcones were prepared to evaluate their peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand-binding activities. Among the three TZDs, one compound possessed PPAR-gamma transactivation potential, while the others showed antagonistic activity against PPAR-gamma transactivation. Among the chalcones, compound 5 was the most potent, and structure-activity relationship studies indicated that a methoxyl group in position C-4 and hydroxyl group in position C-4' or 5' in chalcone plays a key role in determining the potency of PPAR-gamma activation.

Chalcone↗

Inhibitory effects of Irigenin from the rhizomes of Belamcanda chinensis on nitric oxide and prostaglandin E(2) production in murine macrophage RAW 264.7 cells.

In the present study, we investigated antiinflammatory effects of six flavonoids isolated from the rhizomes of Belamcanda chinensis (Iridaceae) in RAW 264.7 macrophages. The results indicated that irigenin concentration dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin (PG) E(2) production. Furthermore, this compound inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 proteins and mRNAs without an appreciable cytotoxic effect. Treatment of the transfectant RAW 264.7 cells with irigenin reduced the level of nuclear factor-kappaB (NF-kappaB) activity, also effectively lowered NF-kappaB binding measured by electrophoretic mobility shift assay (EMSA), which was associated with decreased p65 protein levels in the nucleus. On the basis of the above data, we suggest that the effect of irigenin in decreasing LPS-induced NO and PGE(2) synthesis is due to diminish the mRNA and protein expression of iNOS and COX-2, respectively, also may be due to under the suppression of NF-kappaB activation. Therefore, irigenin isolated from the rhizomes of Belamcanda chinensis could be offered as a leading compound for anti-inflammation.

Animals↗

Inhibition of inducible nitric oxide synthase and cyclooxygenase II by Platycodon grandiflorum saponins via suppression of nuclear factor-kappaB activation in RAW 264.7 cells.

Saponins are glycosidic compounds present in many edible and inedible plants. They exhibit potent biological activities in mammalian systems, including several beneficial effects such as anti-inflammation and immunomodulation. In this study, we investigated the effects of seven platycodin saponins on the activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase II (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. We found that 2"-O-acetyl polygalacin D (S1), platycodin A (S2), platycodin D (S3), and polygalacin D (S6) inhibited LPS-induced NO production in a concentration-dependent manner. Furthermore, these compounds inhibited the expression of LPS-induced iNOS and COX-2 protein and mRNA without an appreciable cytotoxic effect on RAW 264.7 macrophages, and could suppress induction by LPS of pro-inflammatory cytokines such as prostaglandin E2 (PGE2). Treatment with these compounds of RAW 264.7 cells transfected with a reporter construct indicated a reduced level of LPS-induced nuclear factor-kappaB (NF-kappaB) activity and effectively lowered NF-kappaB binding as measured by electrophoretic mobility shift assay (EMSA). The suppression of NF-kappaB activation appears to occur through the prevention of inhibitor kappaB (IkappaB) degradation. In vivo, platycodin saponin mixture (PS) and S3 protected mice from the lethal effects of LPS. The 89% lethality induced by LPS/galactosamine was reduced to 60% and 50% when PS and S3, respectively, were administered simultaneously with LPS. These results suggest that the main inhibitory mechanism of the platycodin saponins may be the reduction of iNOS and COX-2 gene expression through blocking of NF-kappaB activation.

Animals↗

Inhibitory effects of Ganoderma applanatum on rat lens aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues.

Aldose reductase, the key enzyme of the polyol pathway, is known to play important roles in diabetic complications. Therefore, inhibitors of aldose reductase would be potential agents for the prevention of diabetic complications. To evaluate the inhibitory potential of aldose reductase from Ganoderma applanatum (Polyporaceae), methanol (MeOH) and water extracts were tested for their effects on rat lens aldose reductase (RLAR). The effects of both extracts on streptozotocin (STZ)-induced diabetes in rats were also investigated. The MeOH extract exhibited a potent rat lens aldose reductase (RLAR) inhibition in vitro, and showed a significant inhibition, of not only serum glucose concentrations, but also of sorbitol accumulations in the lens, red blood cells (RBC) and sciatic nerves in STZ-induced diabetic rats. Associated with a reduction in serum glucose concentration in STZ-induced diabetic rats, this extract was found to cause a significant glucose tolerance effect. These results suggested that G. applanatum might possess constituents with antidiabetic and inhibitory effects on diabetic complications.

Aldehyde Reductase↗

Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase and tumor necrosis factor-alpha by 2'-hydroxychalcone derivatives in RAW 264.7 cells.

In cultures of the murine macrophage cell line RAW 264.7, effects of four 2'-hydroxychalcone derivatives, 2'-hydroxy-4'-methoxychalcone (compound 1), 2',4-dihydroxy-4'-methoxychalcone (compound 2), 2',4-dihydroxy-6'-methoxychalcone (compound 3) and 2'-hydroxy-4,4'-dimethoxychalcone (compound 4), on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were examined. Compounds 1, 2 and 3 at 3-30microM inhibited the production with almost the same potency. Compound 4 showed no inhibitory activity. Compounds 1, 2 and 3 at 3-30microM inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and TNF-alpha mRNA. To clarify the mechanism involved, effects of compounds 1, 2 and 3 on the activation of nuclear factor (NF)-kappaB and activator protein-1 (AP-1) were examined. Both the LPS-induced activation of NF-kappaB and AP-1 were blocked by compounds 1, 2 and 3 at 3-30microM. Moreover, the three compounds at such concentrations inhibited the LPS-induced IkappaB degradation and the phosphorylation of c-jun N-terminal kinase (JNK) and c-jun. These findings suggest that the inhibition of the LPS-induced production of NO and TNF-alpha by the 2'-hydroxychalcone derivatives is due to the inhibition of NF-kappaB and AP-1 activations.

Animals↗

Anti-oxidant activities of Acanthopanax senticosus stems and their lignan components.

The antioxidant activities of Acanthopanax senticosus stems were evaluated in CCl4-intoxicated rats. The n-butanol fraction from the water extract of the stems, when pretreated orally at 200 mg/kg/day for 7 consecutive days in rats, was demonstrated to exhibit significant increases in antioxidant enzyme activities such as hepatic cytosolic superoxide dismutase, catalase and glutathione peroxidase by 30.31, 19.82 and 155%, respectively. The n-butanol fraction whereas showed a significant inhibition of serum GPT activity (65.79% inhibition) elevated with hepatic damage induced by CCl4-intoxication. Eleutheroside B, a lignan component, isolated from the n-butanol fraction was found to cause a moderate free radical scavenging effect on DPPH, its scavenging potency as indicated in IC50 value, being 58.5 microM. These results suggested that the stems of A. senticosus possess not only antioxidant but also hepatoprotective activities.

Administration, Oral↗

Antioxidant activities of isoflavones from the rhizomes of Belamcanda chinensis on carbon tetrachloride-induced hepatic injury in rats.

The present study was carried out to clarify whether tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis (Iridaceae) inhibit hepatic damage induced by carbon tetrachloride (CCl4)-intoxication in rats by the experimental methods in vitro and in vivo. Tectorigenin and tectoridin exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl4-intoxication in rats, as well as in a lipid peroxidation causing a significant decrease in malondialdehyde (MDA) production by thiobarbituric acid (TBA)-reactant assay. Both compounds also showed strong increase in the antioxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities in CCl4-intoxicated rats. These results suggested that tectorigenin and tectoridin isolated from the rhizomes of B. chinensis possess not only the antioxidative, but also the hepatoprotective activities in CCl4-intoxicated rats.

Alanine Transaminase↗

Antiinflammatory activity of hyperin from Acanthopanax chiisanensis roots.

The chloroform and the ethyl acetate fractions from the roots of Acanthopanax chiisanensis exhibited a significant inhibition of prostaglandin E2 (PGE2) production in rat peritoneal macrophages stimulated by the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). Hyperin was isolated as an active principle from the ethyl acetate fraction. It suppressed not only PGE2 production but also nitric oxide (NO) production in vitro in a concentration dependent manner, their IC50, being 24.3 and 32.9 microM, respectively. Hyperin also caused a significant inhibition of increase in acetic acid-induced vascular permeability in mice in vivo.

Animals↗

New lanostane-type triterpenoids from Ganoderma applanatum.

Four new lanostane-type triterpenes were isolated from the MeOH extract of the fruiting bodies of Ganoderma applanatum. Their structures were established as 3beta,7beta,20,23xi-tetrahydroxy-11,15-dioxolanosta-8-en-26-oic acid (1), 7beta,20,23xi-trihydroxy-3,11,15-trioxolanosta-8-en-26-oic acid (2), 7beta,23xi-dihydroxy-3,11,15-trioxolanosta-8,20E(22)-dien-26-oic acid (3), and 7beta-hydroxy-3,11,15,23-tetraoxolanosta-8,20E(22)-dien-26-oic acid methyl ester (4), respectively, by extensive spectroscopic analyses.

Canada↗

Inhibitory effect of pyridyloxy- or phenoxylphenoxyalkanate derivatives on rat lens aldose reductase and rat platelet aggregation.

The therapeutic potential of aldose reductase inhibitors for the prevention of the secondary complications of diabetes has been extensively reported. On the other hand, the hyperaggregability of platelets in diabetic patients has also been reported as a cause of chronic diabetic complications. The purpose of this study was to develop new compounds with these dual effects from pyridyloxy- or phenoxylphenoxyalkanate synthesized derivatives and examine the effect of their structure-activity relationships on the inhibition of rat lens aldose reductase (RLAR) as well as on platelet aggregation. 2-[4-(2,6-dichloro-3-methyl-phenoxy)-3-nitro-phenoxy]-propionic acid (3) exhibited the most potent inhibitory effect (IC(50) = 3.0 +/- 0.21 microM), comparable to tetramethylene glutaric acid (IC(50) = 6.1 +/- 0.2 microM), which is used as a positive control on RLAR, and showed potent inhibitory activities on rat platelet aggregation induced by ADP and collagen (IC(50) = 0.093 +/- 0.01 and 0.032 +/- 0.01 microM, respectively) comparable with aspirin (IC(50) = 0.15 +/- 0.05 and 0.047 +/- 0.01 microM, respectively), used as a positive control.

Aldehyde Reductase↗

Suppression of tumor growth by a new glycosaminoglycan isolated from the African giant snail Achatina fulica.

Acharan sulfate is a new type of glycosaminoglycan from the giant African snail, Achatina fulica. Acharan sulfate, which has a primary repeating disaccharide structure of alpha-D-N-acetylglucosaminyl-2-O-sulfo-alpha-L-iduronic acid, was studied as a potential antitumor agent in both in vivo and in vitro assays. The antiangiogenic activity of acharan sulfate was evaluated in the chorioallantoic membrane assay and by measuring its effect on the proliferation of calf pulmonary artery endothelial cells. In vivo, a matrigel plug assay showed that acharan sulfate suppressed basic fibroblast growth factor (bFGF)-stimulated angiogenesis and lowered the hemoglobin (Hb) content inside the plug. Acharan sulfate was administered s.c. at two doses for 15 days to C57BL/6 mice implanted with murine Lewis lung carcinoma in the back. It was also administered i.p. to ICR mice bearing sarcoma 180 at a dose of 30 mg/kg. Subcutaneous injection of acharan sulfate at doses of 10 and 30 mg/kg decreased tumor weight and tumor volume by 40% without toxicity or resistance. Intraperitoneal injection of acharan sulfate also decreased tumor weight and volume by 40% in sarcoma 180-bearing mice. These results suggest that the antitumor activity of acharan sulfate may be related to the inhibition of angiogenesis.

Allantois↗

Anti-tumour and immuno-stimulating activities of the fruiting bodies of Paecilomyces japonica, a new type of Cordyceps spp.

The anti-tumor and immuno-stimulating activities of the fruiting bodies of Paecilomyces japonica (PJ), grown on silk-worm larvae and of Cordyceps sinensis (CS), a wild form of Cordyceps Fungi, were investigated. Ethanol extracts of both fungi, when administered for 9 consecutive days, at 50 and 100 mg/kg i.p., caused a significant increase in life span and a significant decrease in tumor weights and volumes, in mice inoculated with Sarcoma-180 tumor cells. Both fungal extracts were demonstrated to exhibit phagocytosis enhancing activity as measured by carbon clearance in mice. PJ extracts, when administered i.p. at 50 mg/kg/day for 3 consecutive days, exhibited a significant enhancement of phagocytosis, its potency as expressed by the regression coefficient ratio, RCtr/RCc, being 1.64 (the phagocytosis index = 2). This was approximately the same for that of zymosan (RCtr/RCc = 1.55, PI = 2), a typical phagocytosis enhancer, whereas CS extracts exhibited a moderate phagocytosis enhancing activity at the same dose level (RCtr/RCc = 1.30, PI = 1). Both fungal extracts caused a significant increase in an acid phosphatase activity, representing lysosomal enzymes, in macrophages at 20 and 100 micro g/ml in vitro, in compliance with in vivo results. These results suggest that the anti-tumor activity of both fungi might be related to an immuno-stimulating function.

Adjuvants, Immunologic↗

Anti-oxidant activities of fucosterol from the marine algae Pelvetia siliquosa.

The anti-oxidant activities of fucosterol isolated from the marine algae Pelvetia siliquosa were investigated. Fucosterol exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl4-intoxication in rats. Fucosterol inhibited the sGOT and sGPT activities by 25.57 and 63.16%, respectively. Fucosterol showed the increase in the anti-oxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities by 33.89, 21.56 and 39.24%, respectively, in CCl4-intoxicated rats. These results suggest that fucosterol possess not only the anti-oxidant, but also the hepatoprotective activities in rats.

Administration, Oral↗

Anti-tumor activities of decursinol angelate and decursin from Angelica gigas.

The in vivo anti-tumor activities of decursinol angelate (1) and decursin (2) isolated from the roots of Angelica gigas were investigated. These two compounds, when administered consecutively for 9 days at 50 and 100 mg/kg i.p. in mice, caused a significant increase in the life span and a significant decrease in the tumor weight and volume of mice inoculated with Sarcoma-180 tumor cells. These results suggest that decursinol angelate (1) and decursin (2) from A. gigas have anti-tumor activities.

Angelica↗

Anti-oxidant activities of the extracts from the herbs of Artemisia apiacea.

The anti-oxidant activities of the various fractions from the herbs of Artemisia apiacea were investigated. The n-hexane and n-butanol fractions were found to cause significant free radical scavenging effects on DPPH, their scavenging potencies as indicated in IC(50) values, being 230.1 and 183.7 microg/ml, respectively. The n-butanol fraction exhibited a significant decrease in serum transaminase activities elevated by hepatic damage induced by CCl(4)-intoxication in rats. All fractions tested exhibited a lipid peroxidation causing a significant decrease in MDA production in TBA-reactant assay. The n-butanol fraction was the strongest in the increase in the anti-oxidant enzymes such as hepatic cytosolic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-px) activities in CCl(4)-intoxicated rats. These results suggest that the herbs of A. apiacea possess not only the anti-oxidant, but also the activities in CCl(4)-intoxicated rats. Especially, the n-butanol extract was found to cause significant increases in the rat liver cytosolic SOD, catalase, GSH-px activities as well as a significant decrease in the MDA production.

Alanine Transaminase↗

Inhibitory effects of furanocoumarins isolated from the roots of Angelica dahurica on prostaglandin E2 production.

We have isolated five furanocoumarins, byakangelicin, phellopterin, imperatorin, isoimperatorin, and oxypeucedanin methanolate, from the roots of Angelica dahurica (Umbelliferae) and prepared five semi-synthesized compounds by the partial reduction of each isolated furanocoumarin, and the effects of these compounds on lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2 ) production in rat peritoneal macrophages were examined. Among these compounds, imperatorin showed the most potent inhibitory activity on the LPS-induced PGE2 production. It also inhibited the LPS-induced expressions of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES). These findings suggest that the inhibitory effect of furanocoumarins on the LPS-induced PGE2 production is due to the inhibition of the expression of COX-2 and mPGES.

Angelica↗