Tae Yong Shin

Acetylcholinesterase inhibitors from the aerial parts ofCorydalis speciosa

In a bioassay-guided search for acetylcholinesterase inhibitors from Korean natural resources, four isoquinoline alkaloids, corynoxidine (1), protopine (2), palmatine (3), and berberine (4) have been isolated from the methanolic extract of the aerial parts ofCorydalis speciosa. Structures of these compounds were elucidated on the basis of spectroscopic techniques. These compounds inhibited acetylcholinesterase activity in a dose-dependent manner, and the IC50 values of compounds1-4 were 89.0, 16.1, 5.8, and 3.3 μM, respectively.

Inhibitory effect of mast cell-dependent anaphylaxis byGleditsia sinensis

We investigated the effect of aqueous extract ofGleditsia sinensis thorns (Leguminosae) (GSAE) on the mast cell-dependent anaphylaxis. GSAE (0.005 to 1 g/kg) also sigendently inhibited systemic anaphylaxis induced by compound 48/80 in rats. GSAE (0.1 and 1 g/kg) also significantly inhibited local anaphylaxis activated by anti-DNP IgE. When GSAE was pretreated at the same concentrations with systemic anaphylaxis, the plasma histamine levels were reduced in a dose-dependent manner. GSAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, When GSAE (1 mg/ml) was added, transiently and significantly increased about fourfold compared with that of basal cells. Moreover, GSAE (0.01 and 0.1 mg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-α production from RPMC. These results suggest a possible use of GSAE in managing mast cell-dependent anaphylaxis.

Anti-allergic components from the peels ofCitrus unshiu

In a bioassay-guided search for anti-allergic compounds from higher plants of Korea, polymethoxyflavones, 3′,4′,5,6,7,8-hexamethoxyflavone (I), 5-hydroxy-3′,4′,6,7,8-pentamethoxyflavone (II) and 3′,4′,5,7,8,-pentamethoxyflavone (III) have been isolated from the immature peels ofCitrus unshiu. Structures of these compounds were elucidated on the basis of spectroscopic techniques. CompoundsI andII inhibited dose-dependently histamine release from the rat peritoneal mast cells activated by compound 48/80 or anti-DNP IgE.

Cytotoxic isoquinoline alkaloids from the aerial parts ofCorydalis incisa

Three known isoquinoline alkaloids were isolated from the chloroform-soluble fraction of the methanolic extract of the aerial parts ofCorydalis incisa (Papaveraceae) through repeated column chromatography. Their chemical structures were elucidated as corynoline (1), corynoloxine (2) and 6-oxocorynoline (3) using spectroscopic analysis. Compounds 1-3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2 and HCT15 tumor cells.

Prostaglandin E2-mediated dysregulation of proinflammatory cytokine production in pristane-induced lupus mice.

Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. PGE2 modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of PGE2 in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether PGE2 mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL PGE2 and LPS-stimulated production of PGE2 by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous PGE2 enhanced production of IL-6, IL-10, and NO but decreased TNF-α by macrophages and augmented IFN-γ, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous PGE2 also enhanced production of IFN-γ, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a PGE2 synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced TNF-α. Indo remarkably inhibited Con A-increased production of IFN-γ, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous PGE2 may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and IFN-γ, and NO in pristane-induced lupus mice.

Antiallergic action of Magnolia officinalis on immediate hypersensitivity reaction

We studied the effect of aqueous extract ofMagnolia officinalis bark (Magnoliaceae) (MOAE) on the immediate hypersensitivity reaction. MOAE (0.01 to 1 g/kg) dose-depen-dently inhibited compound 48/80 induced systemic anaphylaxis in rats. MOAE (0.1 and 1 g/kg) also significantly inhibited local immunoglobulin E (IgE)-mediated passive cutaneous anaphylactic reaction. When MOAE was pretreated at concentrations ranging from 0.01 to 1 g/kg, the levels of plasma histamine were reduced in a dose-dependent manner. MOAE (0.001 to 1 mg/ml) dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-dinitrophenyl (DNP) lgE. The level of cyclic AMP (cAMP) in RPMC, when MOAE was added, significantly increased compared with that of the normal control. Moreover, MOAE (0.01 to 1 mg/ml) had a significant inhibitory effect on anti-DNP lgE-induced tumor necrosis factor-α production from RPMC. These results indicate that MOAE inhibits immediate hypersensitivity reactionin vivo andin vitro.

Anti-metastatic properties of the leaves of Eriobotrya japonica

The leaves of Eriobotrya japonica Lindl. have been widely used as a traditional medicine for the treatment of many diseases including gastroenteric disorders, diabetes mellitus, chronic bronchitis and asthma. In the present study, the anti-metastatic action of the EtOAc fraction of the leaves of E. japonica (LEJ) was investigated. LEJ showed potent inhibitory effects on MMP-2 and MMP-9 activities and expressions via down-regulation of NF-κB translocation to the nucleus in B16F10 cells. In addition, the cell migration and invasion were down-regulated by LEJ. LEJ also significantly suppressed lung metastasis in vivo. Moreover, we isolated the compounds ursolic acid and 2α-hydroxyursolic acid from LEJ and both compounds also significantly suppressed MMP-2 and MMP-9 activities, indicating that they are the active components of LEJ. The present results demonstrate that LEJ may be used as valuable antimetastatic agent for the treatment of cancer metastasis.

Immunoregulatory abnormalities of T cells and hyperreactivity of B cells in theIn Vitro immune response in pristane-induced lupus mice

Systemic lupus erythematosus (SLE) is characterized by overactive B cells that differentiate into autoantibody-forming cells, aberrant T cell function that provides helping B cells produce autoantibodies, and overproduction of proinflammatory cytokines. However, immunodysregulation in lupus pathogenensis remains incomplete. We examined mitogen-stimulated production of proinflammatory cytokines, cell proliferation, T cell activation, and T cell apoptosisin vitro in pristane-induced lupus BALB/c mice compared to normal mice. LPS-stimulated production of IL-6 and IL-10 by splenocytes and macrophages from pristane-induced lupus mice were remarkably up-regulated compared to normal mice, whereas production of macrophage TNF-α was significantly down-regulated. Moreover,in vitro production of IL-2, IL-6, IL-10 and IFN-γ by Con A-stimulated splenocytes, cell proliferation in LPS- or Con A-stimulated- thymocytes and splenocytes, and expression of CD69+CD4+ T cells in Con A-stimulated splenocytes were greatly increased in cells derived from pristane-induced lupus mice compared to normal mice. In addition, splenic T cells and CD4+ T cells in thymocytes from pristane-induced lupus mice were more resistant than nonautoimmune normal cells to Con A-induced apoptosis. Our findings indicate that immunoregulatory abnormalities of T cells and hyperreactivity of B cells in thein vitro immune responses in pristane-induced lupus mice may explain some of lupus pathogenesis.

Pentacyclic triterpenoids fromllex macropoda

Six compounds were isolated from the twigs ofIlex macropoda. Their structures were elucidated as betulinic acid, lupeol, betulone, betulin, erythrodiol and 11-oxo-erythrodiol by physicochemical and spectroscopic analysis. Among them, lupeol, betulone, erythrodiol and 11-oxo-erythrodiol were isolated for the first time from this plant.

Effects of isolated compounds from Catalpa ovata on the T cell-mediated immune responses and proliferation of leukemic cells

Three compounds were isolated from the ethyl acetate soluble fraction of the methanolic extract of the leaves of Catalpa ovata (Bignoniaceae) through repeated column chromatography. We investigated the effects of these compounds on T cell-mediated responses for tumor surveillance and proliferation in U937, HL60, and Molt-4 leukemia cells. Compounds 1–3 inhibited proliferation of those cells in a dose-dependent manner. Compound 3 showed mild effect in Molt-4 cell cytotoxicity. Compound 3 enhanced gene expressions of p53 and IL-4, but decreased IL-2 and IFN-Γ genes in Molt-4 cell. Our findings indicate that compound 3 may enhance T cell-mediated immune responses and anticancer properties.