Eon-Jeong Lee

Inhibitory action of water soluble fraction of Terminalia chebula on systemic and local anaphylaxis

We investigated the effects of the water soluble fraction of Terminalia chebula (Combretaceae) (WFTC) on systemic and local anaphylaxis. WFTC administered 1h before compound 48/80 injection inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.01-1.0 g/kg. When WFTC was administered 5 or 10 min after compound 48/80 injection, the mortality also decreased in a dose-dependent manner. Passive cutaneous anaphylaxis was inhibited by 63.5+/-7.8% by oral administration of WFTC (1.0 g/kg). When WFTC was pretreated at concentrations ranging from 0.005 to 1.0 g/kg, the serum histamine levels were reduced in a dose-dependent manner. WFTC (0.01-1.0 mg/ml) also significantly inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. However, WFTC (1.0 mg/ml) had a significant increasing effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that WFTC may possess a strong antianaphylactic action.

Effect of the aqueous extract of Aquilaria agallocha stems on the immediate hypersensitivity reactions

We investigated the effects of the aqueous extract of Aquilaria agallocha Roxb. (Thymelaeaceae) on the immediate hypersensitivity reactions. The aqueous extract of Aquilaria agallocha stems showed inhibitory effects on passive cutaneous anaphylaxis, anaphylaxis induced by compound 48/80, and histamine release from rat peritoneal mast cells (RPMC). The morphological examination also clearly showed that the extract prevented the degranulation of RPMC in rats. The level of compound 48/80-induced intracellular cAMP in RPMC, when the extract was added, significantly increased about 8-fold at 10 s compared with that of basal cells. These results suggest that the aqueous extract of Aquilaria agallocha stems inhibits the immediate hypersensitivity reaction by inhibition of histamine release from mast cells.

Inhibition of nitric oxide synthesis by butanol fraction of the methanol extract of Ulmus davidiana in murine macrophages

Since there is increasing evidence that nitric oxide (NO) plays a crucial role in the pathogenesis of inflammatory diseases, this study was undertaken to address whether the methanol (MeOH) extract and its fractions of the bark of Ulmus davidiana Planch (Ulmaceae) could modulate the expression of inducible NO synthase (iNOS) in thioglycollate-elicited murine peritoneal macrophages and murine macrophage cell line, RAW264.7 cells. Stimulation of the peritoneal macrophages and RAW264.7 cells with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) resulted in increased production of NO in the medium. However, the butanol (BuOH) fraction of the MeOH extract of U. davidiana barks showed marked inhibition of NO synthesis in a dose-dependent manner. The inhibition of NO synthesis was reflected in the decreased amount of iNOS protein, as determined by Western blotting. The BuOH fraction did not affect the viability of RAW264.7 cells, as assessed by methylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide (MTT) assay; rather, it reduced endogenous NO-induced apoptotic cell death via inhibition of NO synthesis in RAW264.7 cells. On the other hand, the BuOH fraction showed no inhibitory effect on the synthesis of NO by RAW264.7 cells, when iNOS was already expressed by the stimulation with IFN-gamma and LPS. Collectively, these results demonstrate that the BuOH fraction inhibits NO synthesis by inhibition of the induction of iNOS in murine macrophages.

Forsythia fructus Inhibits the Mast-Cell-Mediated Allergic Inflammatory Reactions

Mast cells are key as effector cells in the early phase allergic inflammation and in diverse immunological and pathological processes. Forsythia fructus (F. fructus) has used as a traditional medicine for inflammatory diseases. In the present study, we determined the effect of F. fructus extracts on compound 48/80-induced paw oedema and vascular permeability in vivo. In addition, we investigated in vitro whether F. fructus has inhibitory effects on compound 48/80-induced histamine releases from rat peritoneal mast cells (RPMC), and on phorbol 12-myristate 13-acetate (PMA) plus A23187-induced tumor necrosis factor-α (TNF-α) releases from human mast cells (HMC-1). In mice orally administrered F. fructus (100 μg/g) for 1 h, compound-48/80-induced oedema and vascular permeability were significantly reduced rather than those receiving intravenous injection of ketotifen, mast cell stabilizer. F. fructus dose-dependently inhibited the histamine release induced by compound 48/80 from RPMCs. Moreover, F. fructus had no cytotoxic effects on cell viability and had inhibitory effects on TNF-α secretion from HMC-1. These results suggest that F. fructus is a potential herb medicine for treatment of inflammatory diseases through downmodulating mast cell activation.

Inhibition of immediate-type allergic reaction by Rosa davurica Pall. in a murine model.

We studied the effect of Rosa davurica Pall. (Rosaceae) fruits (RdF) on immediate-type allergic reactions. RdF completely inhibited compound 48/80-induced systemic anaphylactic shock at the dose of 1 g/kg. When RdF was given as pretreatment, at concentrations ranging from 0.0001 to 1 g/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. RdF inhibited the passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody dose dependently. RdF also inhibited the histamine release induced by compound 48/80 or anti-DNP IgE from the rat peritoneal mast cells (RPMC). Moreover, RdF had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that RdF may contain compounds with actions that inhibit mast cell degranulation in the rat.

Administration of Dehydroepiandrosterone Reverses the Immune Suppression Induced by High Dose Antigen in Mice

Several factors including antigen concentration, the route of antigen administration, hormones and cytokines have shown to affect T cells to produce the distinct patterns of lymphokines which exert regulatory and effector functions of immune response. In this study, we asked whether administration of dehydroepiandrosterone (DHEA) to mice which were tolerized by high dose of antigen could modulate T cell functions to restore the suppressed cellular immune response and to produce the distinct lymphokines. An intravenous injection of high dose of sheep red blood cells induced suppression of delayed type hypersensitivity (DTH) and a single subcutaneous injection of the tolerant mice with DHEA restored the suppressed DTH response. Furthermore, in vitro treatment of spleen cells from tolerant mice with DHEA abolished the transfer of tolerance to naive recipients. Lymphocytes from the DHEA-treated tolerant mice produced more IFN-gamma and less IL-4 and IL-6 than the cells from tolerant animals without DHEA treatment. These findings indicate that DHEA could recover antigen-specific immune suppression by differentially affecting T cells to produce the distinct lymphokines.

12-O-tetradecanoyl phorbol 13-acetate, protein kinase C (PKC) activator, protects human leukemia HL-60 cells from taxol-induced apoptosis: possible role for extracellular signal-regulated kinase.

Abstract The purpose of this study was to evaluate whether the mitogen-activated protein kinase / extracellular signal-regulated kinase (MEK) signaling pathway contributes to 12-O-tertadecanoyl phorbol 13-acetate (TPA)mediated protection from taxol-induced apoptosis of human leukemia HL-60 cells. Treatment of cells with taxol for 12 h resulted in apoptosis of HL-60 cells. TPA was protective against taxol-induced apoptosis and this anti-apoptotic effect was reversible when TPA was used in conjunction with staurosporine and H-7, PKC inhibitors, suggesting that TPA may protect HL-60 cells against taxol-induced apoptosis via the PKC-dependent pathway. Since TPA stimulates MEK signal transduction pathway in HL-60 cells, we postulated that MEK pathway may be playing a role in the ability of TPA to inhibit taxol-induced apoptosis. PD098059, a specific MEK kinase inhibitor, abolished the ability of TPA to inhibit taxol-induced apoptosis. These results suggest that activation of PKC in HL-60 cells confers protection against taxol-induced apoptosis and that MEK mediates anti-apoptotic signaling of PKC.

Solanum lyratum inhibits anaphylactic reaction and suppresses the expression of L-histidine decarboxylase mRNA.

We investigated the effect of aqueous extract of Soloanum lyratum THUNB. (Solanaceae) (SLAE) on anaphylactic reaction. The mast cell is widely thought to contribute to the acute changes associated with anaphylaxis. SLAE inhibited skin mast cells-mediated anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. SLAE dose-dependently inhibited histamine release in mouse peritoneal mast cells activated by anti-DNP IgE or substance P. Substance P increased steady state levels of L-histidine decarboxylase (HDC) mRNA in mouse mastocytoma P-815 cells. Northern-blot analysis demonstrated that significantly reduced level of the mRNA of HDC was expressed in mast cells treated with SLAE, compared to that without SLAE. We conclude that SLAE directly affect IgE-mediated anaphylactic reaction and substance P-induced HDC mRNA over-expression.

Effect of Bojungikki‐tang on Lipopolysaccharide‐Induced Cytokine Production from Peripheral Blood Mononuclear Cells of Chronic Fatigue Syndrome Patients

Abstract Bojungikki‐tang (BIT) has been widely used to treat patients suffering from chronic fatigue syndrome (CFS). However, its effect has not been yet investigated experimentally. Based upon the clinical presentation of CFS, we hypothesized that cytokines may play a role in the pathogenesis of the disease. We studied the effect of BIT on lipopolysaccharide (LPS)‐induced various cytokines production in peripheral blood mononuclear cells (PBMC) of CFS patients. Bojungikki‐tang (1 mg/mL) significantly inhibited LPS‐induced tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, IL‐10, transforming growth factor (TGF)‐β1 production by 63.55% ± 0.19%, 55.06% ± 0.27%, 48.23% ± 0.48%, 54.09% ± 0.76%, respectively (P < 0.05). Bojungikki‐tang showed a slightly lower inhibitory effect of LPS‐induced Interferon (IFN)‐γ production. These results suggest that BIT may be useful in treating fatigue associated with chronic diseases.

The stem of Sinomenium acutum inhibits mast cell-mediated anaphylactic reactions and tumor necrosis factor-α production from rat peritoneal mast cells.

The aqueous extract of Sinomenium acutum stem (SSAE) (0.1-1000 mg/kg) dose-dependently inhibited systemic anaphylactic reaction induced by compound 48/80 in mice. In particular, SSAE reduced compound 48/80-induced anaphylactic reaction with 50% at the dose of 1000 mg/kg. SSAE (100-1000 mg/kg) also significantly inhibited local anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. When mice were pretreated with SSAE at a concentration ranging from 0.1 to 1000 mg/kg, the plasma histamine levels were reduced in a dose-dependent manner. SSAE (1-1000 microg/ml) dose-dependently inhibited histamine release from the rat peritoneal mast cells (RPMCs) activated by compound 48/80 or anti-DNP IgE. In addition, SSAE (0.1 microg/ml) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha (TNF-alpha) production. These results indicate that SSAE inhibits mast cell-mediated anaphylactic reactions and TNF-alpha production from mast cells.