Biomedical subjects

Man Hee Rhee

Publications and source records attributed to Man Hee Rhee.

10 recordsLinked to original sources

PubMed2006

Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation in a cyclic AMP- and cyclic GMP-dependent manner.

Cordycepin (3'-deoxyadenosine) is isolated from Cordyceps militaris, a species of the fungal genus Cordyceps. Cordycepin is an ingredient used in traditional Chinese medicine and is prescribed for various diseases, such as cancer and chronic inflammation. In this study, we investigated the novel effect of cordycepin (3'-deoxyadenosine) on collagen-induced human platelet aggregation. Cordycepin inhibited dose-dependently collagen-induced platelet aggregation in the presence of various concentrations of exogenous CaCl(2). Of two aggregation-inducing molecules, cytosolic free Ca(2+) ([Ca(2+)](i)) and thromboxane A(2) (TXA(2)), cordycepin (500 microM) blocked the up-regulation of [Ca(2+)](i), by up to 74%, but suppressed TXA(2) production by 46%. Subsequently, Ca(2+)-dependent phosphorylation of both 47-kDa and 20-kDa proteins in collagen-treated platelets was potently diminished by cordycepin. However, upstream pathways for producing these two inducers, such as the activation of phospholipase C-gamma2 (PLC-gamma2) (assessed by the phosphotyrosine level) and the formation of inositol 1,4,5-trisphosphate (IP(3)), were not altered by cordycepin. Cordycepin increased the level of second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in collagen-stimulated platelets. Whereas the NO-sensitive guanylyl cyclase inhibitor ODQ did not alter the cordycepin-induced up-regulation of cGMP, the adenylyl cyclase inhibitor SQ22536 completely blocked the cAMP enhancement mediated by cordycepin, indicating that cordycepin had different modes of action. Therefore, our data suggest that the inhibitory effect of cordycepin on platelet aggregation might be associated with the down-regulation of [Ca(2+)](i) and the elevation of cAMP/cGMP production.

Calcium↗

PubMed2006

The inhibitory effect of triterpenoid glycosides originating from Sanguisorba officinalis on tissue factor activity and the production of TNF-alpha.

We examined the inhibitory effects of novel triterpene glycoside compounds [ziyu-glycoside II (ZY-II) and its methyl ester (ZYM-201)], which originated from the roots of sanguisorba officinalis L. (Rosaceae), on tissue factor (TF) activity and tumor necrosis factor (TNF)-alpha production. In in vitro TF activity tests, ZY-II but not ZYM-201 strongly blocked lung TF activity with an IC50 value of 0.46 microM. By contrast, only ZYM-201 dose-dependently inhibited in vivo TF activity with an ED50 value of 1.7 mg/kg, when orally administered. Furthermore, ZYM-201 diminished both in vitro and in vivo TNF-alpha production with IC50 or ED50 values of 69.4 microM and 87.4 mg/kg, respectively. Therefore, these results suggest either that ZYM-201 may be developed as a potent inhibitor of both TF- and TNF-alpha-mediated diseases such as atherosclerosis and septic shock, or it may be a lead compound to be derivatized for further improvement of its curative efficacy.

Administration, Oral↗

PubMed2006

Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia.

Curcumin has been shown to exhibit anti-inflammatory, antimutagenic, and anticarcinogenic activities. However, the modulatory effect of curcumin on the functional activation of primary microglial cells, brain mononuclear phagocytes causing the neuronal damage, largely remains unknown. The current study examined whether curcumin influenced NO production in rat primary microglia and investigated its underlying signaling pathways. Curcumin decreased NO production in LPS-stimulated microglial cells in a dose-dependent manner, with an IC(50) value of 3.7 microM. It also suppressed both mRNA and protein levels of inducible nitric oxide synthase (iNOS), indicating that this drug may affect iNOS gene expression process. Indeed, curcumin altered biochemical patterns induced by LPS such as phosphorylation of all mitogen-activated protein kinases (MAPKs), and DNA binding activities of nuclear factor-kappaB (NF-kappaB) and activator protein (AP)-1, assessed by reporter gene assay. By analysis of inhibitory features of specific MAPK inhibitors, a series of signaling cascades including c-Jun N-terminal kinase (JNK), p38 and NF-kappaB was found to play a critical role in curcumin-mediated NO inhibition in microglial cells. The current results suggest that curcumin is a promising agent for the prevention and treatment of both NO and microglial cell-mediated neurodegenerative disorders.

Animals↗

PubMed2006

Mechanism of isoproterenol-induced RGS2 up-regulation in astrocytes.

Regulators of G protein signaling (RGSs) are inducibly expressed in response to various stimuli and the up-regulation of RGSs leads to significant decreases in GPCR responsiveness. Isoproterenol, an adrenergic receptor agonist, stimulated RGS2 mRNA in C6 rat astrocytoma cells. The up-regulation of RGS2 mRNA was abrogated by genistein, a protein tyrosine kinase inhibitor (PTK), and by broad-spectrum protein kinase C (PKC) inhibitors (staurosporine and GF109203X). alpha-Adrenergic antagonist (prazocin), beta-adrenergic antagonist (prazocin), and pertussis toxin only partially blocked the RGS2 up-regulation, suggesting that the RGS2 up-regulation is concomitantly mediated by Galphai, Galphas, and Galphaq. It is interesting to note that SB203580, a potent p38 mitogen-activated protein kinase (MAPK) inhibitor, completely inhibited the isoproterenol-mediated RGS2 expression. In addition, isoproterenol also markedly stimulated RGS2 mRNA in rat primary astrocytes, which were sensitive to SB203580 and staurosporine. Therefore, our data suggest that adrenergic receptor-mediated signaling (induced by isoproterenol) may be involved in the regulation of RGS2 expression in astrocytes via activating PTK, PKC, and p38 MAPK.

Animals↗

PubMed2006

The expression patterns of RGS transcripts in platelets.

Regulators of G protein signalling (RGS) are involved in the negative regulation of cell activation processes and are involved in the pathophysiology of cardiovascular diseases. To get some further evidence for a role of RGS proteins in platelets, we determined the expression profile of RGS-specific mRNA in rat platelets using reverse transcription-polymerase chain reaction (RT-PCR) with a poly dT18 primer and transcript-specific primers. We found that RGS2, RGS3, RGS5, RGS6, RGS10, RGS14, RGS16 and RGS18, Leukemia-associated Rho-GEF factor (LARG), and Galpha interacting protein (GAIP) were differentially expressed in platelets. The highest expression rate was found for RGS18 (about 1.3 fold when compared to GAPDH), followed by LARG, RGS6, RGS10 and RGS16 (0.7 to 0.95), whereas expression rates for RGS2, RGS3, RGS5, RGS14, and GAIP were in a range of 0.1 to 0.3. Our results suggest that G-protein-coupled receptor-mediated signalling in platelet may be regulated mainly by RGS 18, 16, 10, 6, and LARG.

Animals↗

PubMed2006

Surfactin C inhibits platelet aggregation.

This study was designed to investigate the effect of surfactin C, which is derived from Bacillus subtilis, on platelet aggregation and homotypic leucocyte aggregation. Surfactin C strongly and dose-dependently inhibited platelet aggregation, which was stimulated both by thrombin (0.1 U mL(-1)), a potent agonist that activates the G protein-coupled protease receptor, and by collagen (5 microg mL(-1)), a potent ligand that activates alpha(IIb)beta(3) with IC50 values (concentration inhibiting platelet aggregation by 50%) of 10.9 and 17.0 microM, respectively. Moreover, surfactin C significantly suppressed the intracellular Ca(2+) mobilization in thrombin-activated platelets. Surfactin C, however, did not affect various integrin-mediated U937 cell aggregation, implying that the anti-platelet activity of surfactin C was not due to its detergent effect but by its action on the downstream signalling pathway. Therefore, the results suggest that surfactin C may have a beneficial therapeutic effect on aberrant platelet aggregation-mediated cardiovascular diseases.

Animals↗

PubMed2005

In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts.

Cinnamomum camphora Sieb (Lauraceae) has long been prescribed in traditional medicine for the treatment of inflammation-related diseases such as rheumatism, sprains, bronchitis and muscle pains. In this study, therefore, we aimed to investigate the inhibitory effects of Cinnamomum camphora on various inflammatory phenomena to explore its potential anti-inflammatory mechanisms under non-cytotoxic (less than 100 microg/ml) conditions. The total crude extract (100 microg/ml) prepared with 80% methanol (MeOH extract) and its fractions (100 microg/ml) obtained by solvent partition with hexane and ethyl acetate (EtOAc) significantly blocked the production of interleukin (IL)-1 beta, IL-6 and the tumor necrosis factor (TNF)-alpha from RAW264.7 cells stimulated by lipopolysaccharide (LPS) up to 20-70%. The hexane and EtOAc extracts (100 microg/ml) also inhibited nitric oxide (NO) production in LPS/interferon (IFN)-gamma-activated macrophages by 65%. The MeOH extract (100 microg/ml) as well as two fractions (100 microg/ml) prepared by solvent partition with n-butanol (BuOH) and EtOAc strongly suppressed the prostaglandin E(2) (PGE(2)) production in LPS/IFN-gamma-activated macrophages up to 70%. It is interesting to note that hexane, BuOH and EtOAc extracts (100 microg/ml) also inhibited the functional activation of beta1-integrins (CD29) assessed by U937 homotypic aggregation up to 70-80%. Furthermore, EtOAc and BuOH extracts displayed strong anti-oxidative activity with IC(50) values of 14 and 15 microM, respectively, when tested by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and xanthine oxide (XO) assays. Taken together, these data suggest that the anti-inflammatory actions of Cinnamomum camphora may be due to the modulation of cytokine, NO and PGE(2) production and oxidative stress, and of the subfractions tested, the EtOAc extract may be further studied to isolate the active anti-inflammatory principles.

Anti-Inflammatory Agents↗

PubMed2004

Cytotoxic and pro-apoptotic activities of cynaropicrin, a sesquiterpene lactone, on the viability of leukocyte cancer cell lines.

Cynaropicrin, a sesquiterpene lactone from Saussurea lappa, has been reported to possess immunomodulatory effects on cytokine release, nitric oxide production and immunosuppressive effects. In this study, we have examined cytotoxic effect of cynaropicrin against several types of cell lines such as macrophages, eosinophils, fibroblasts and lymphocytes. Cynaropicrin potently inhibited the proliferation of leukocyte cancer cell lines, such as U937, Eol-1 and Jurkat T cells, but some other cells such as Chang liver cells and human fibroblast cell lines were not strongly suppressed by cynaropicrin treatment. The cytotoxic effect of cynaropicrin was due to inducing apoptosis and cell cycle arrest at G1/S phase, according to flow-cytometric, DNA fragmentation and morphological analyses using U937 cells. Evidence that combination treatment with l-cysteine and N-acetyl-l-cysteine, reactive oxygen species scavengers, or rottlerin (1-[6-[(3-acetyl-2,4,6-trihydroxy-5-methylphenyl)methyl]-5,7-dihydroxy-2, 2-dimethyl-2H-1-benzopyran-8-yl]-3-phenyl-2-propen-1-one), a specific protein kinase (PK) Cdelta inhibitor, abolished cynaropicrin-mediated cytotoxicity and morphological change, and that cynaropicrin-induced proteolytic cleavage of PKCdelta suggests that reactive oxygen species and PKCdelta may play an important role in mediating pro-apoptotic activity by cynaropicrin. Taken together, these results indicate that cynaropicrin may be a potential anticancer agent against some leukocyte cancer cells such as lymphoma or leukemia, through pro-apoptotic activity.

Antineoplastic Agents↗

PubMed2004

Cynaropicrin, a sesquiterpene lactone, as a new strong regulator of CD29 and CD98 functions.

Cynaropicrin is a sesquiterpene lactone displaying immunomodulatory effects on the production of cytokine and nitric oxide from macrophages/monocytes. In this study we have examined inhibitory effect of cynaropicrin on activation of major adhesion molecules [CD29 (beta1 integrins), CD43, and CD98] on the cells assessed by U937 (promonocytic cells) homotypic aggregation. Cynaropicrin potently blocked CD29 (beta1 integrins)- and CD98-induced homotypic aggregation with IC(50) values of 3.46 and 2.98 microM, respectively, without displaying cytotoxicity. Similarly, flow cytometric analysis exhibited that cynaropicrin down-regulated strikingly surface level of CD29 and CD147, a functional regulator of CD98, but not CD43. More importantly, cynaropicrin inhibition was linked to blockade of extracellular signal-related kinase (ERK) activation and distinct from other enzyme inhibitors including rottlerin, propranolol, forskolin, and chloroquine, but not cytochalasin B. Therefore, our finding is the first demonstration that cynaropicrin may be a potent functional regulator of CD29 and CD98 via interrupting ERK activation which may be linked to cytoskeleton rearrangement, suggesting further application to CD29- and CD98-mediated diseases such as virus-induced chronic inflammation, and invasion, migration, and metastasis of leukocyte cancer cells.

Antigens, CD↗

PubMed2003

In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges.

(3 S,14 S)-Petrocortyne A, a lipid compound (a C(46) polyacetylenic alcohol), from marine sponges ( Petrosia sp.) is potently cytotoxic against several solid tumour cells. In this study, we investigated in vitro anti-inflammatory and pro-aggregative effects of petrocortyne A at non-cytotoxic concentrations on various cellular inflammatory phenomena using the macrophage and monocytic cell lines RAW264.7 and U937. Petrocortyne A blocked tumour necrosis factor-alpha (TNF-alpha) production strongly and concentration-dependently in lipopolysaccharide (LPS)-activated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)/LPS-treated U937 cells. It also blocked NO production concentration-dependently in LPS- or interferon (IFN)-gamma-treated RAW264.7 cells. Among the migration factors tested, the compound selectively blocked the expression of hepatocyte growth factor/scatter factor (HGF/SF). On the other hand, as assessed by a cell-cell adhesion assay, petrocortyne A did not block the activation of adhesion molecules induced by aggregative antibodies to adhesion molecules, but suppressed PMA-induced cell-cell adhesion significantly. Intriguingly, petrocortyne A induced U937 homotypic aggregation following long exposure (2 and 3 days), accompanied by weak induction of pro-aggregative signals such as tyrosine phosphorylation of p132 and phosphorylation of extracellular signal-related kinase 1 and 2 (ERK 1/2). Petrocortyne A may thus inhibit cellular inflammatory processes and immune cell migration to inflamed tissue.

Acetylene↗