Seung-Heon Hong

Effect of Syzygium aromaticum extract on immediate hypersensitivity in rats

We investigated the effect of aqueous extract of Syzygium aromaticum (L.) Merr. et Perry (Myrtaceae) flower bud (SAFB) on immediate hypersensitivity. SAFB inhibited compound 48/80-induced systemic anaphylaxis in rats (IC50 = 31.25 mg/kg, i.p.). SAFB also inhibited local immunoglobulin E (IgE)-mediated passive cutaneous anaphylactic reaction (IC50 = 17.78 mg/kg, i.v.; IC50 = 19.81 mg/kg, p.o.). When SAFB was pretreated at concentrations ranging from 25 to 1000 mg/kg, the serum histamine levels were reduced in a dose-dependent manner. Moreover, SAFB dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80 or anti-dinitrophenyl IgE. When SAFB was added, the level of cAMP in RPMC transiently and significantly increased about 47-fold at 10 s compared with that of basal cells. These results indicate that SAFB inhibits immediate hypersensitivity by inhibition of histamine release from mast cells in vivo and in vitro.

Role of Ca2+ on TNF-α and IL-6 secretion from RBL-2H3 mast cells

Abstract Ca2+ acts as an important second messenger in mast cells. However, the mechanisms involved in the secretion of inflammatory cytokines from activated mast cells are unknown. In this study, we examined the signaling pathway involved in calcium-related cytokine secretion in a mast cell line, RBL-2H3 cells. We report that treatment with 1,2-bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester (BAPTA-AM), a chelator of intracellular calcium, can inhibit IgE-stimulated TNF-α and IL-6 secretion in a concentration-dependent manner with IC50 values of 0.41 and 0.014 μM, respectively. Maximal inhibition of TNF-α and IL-6 secretion was 58.5±3% and 87±8% in BAPTA-AM, respectively. BAPTA-AM also completely inhibited the IgE-induced TNF-α and IL-6 mRNA levels. In activated RBL-2H3 cells, the expression level of NF-κB/Rel A protein increased in the nucleus. However, the level of NF-κB/Rel A in nucleus was decreased by treatment of BAPTA-AM. In addition, BAPTA-AM completely inhibited the IgE-induced IκB kinase β (IKKβ) activation and IκBα phosphorylation. These observations demonstrate that the intracellular Ca2+ may play an important role in IgE-induced TNF-α and IL-6 secretion from mast cells via IKKβ activation.

Anti-Inflammatory Activity of Hyperoside Through the Suppression of Nuclear Factor-κB Activation in Mouse Peritoneal Macrophages

Hyperoside (quercetin-3-O-galactoside) is a flavonoid compound mainly found in the herb plants Hypericum perforatum L and Crataegus pinnatifida. Although hyperoside has a variety of pharmacological effects including anti-viral, anti-oxidative, and anti-apoptotic activities, the anti-inflammatory mechanism of hyperoside in mouse peritoneal macrophages remains unclear. In this study, hyperoside was shown to exert an anti-inflammatory action through suppressed production of tumor necrosis factor, interleukin-6, and nitric oxide in lipopolysaccharide-stimulated mouse peritoneal macrophages. The maximal inhibition rate of tumor necrosis factor-α, interleukin-6, and nitric oxide production by 5 μM hyperoside was 32.31 ± 2.8%, 41.31 ± 3.1%, and 30.31 ± 4.1%, respectively. In addition, hyperoside inhibited nuclear factor-κB activation and IκB-α degradation. The present study suggests that an important molecular mechanism by hyperoside reduces inflammation, which might explain its beneficial effect in the regulation of inflammatory reactions.

Alginic acid has anti-anaphylactic effects and inhibits inflammatory cytokine expression via suppression of nuclear factor-kappaB activation.

Background Alginic acid is comprised of complex polymerized polysaccharides, and can be chemically extracted from seaweed. Alginic acid has an inhibitory effect on histamine release, but its molecular mechanisms are not well understood.

The Beneficial Effect of Vanillic Acid on Ulcerative Colitis

Vanillic acid, an oxidized form of vanillin, is a benzoic acid derivative used as a flavoring agent. The objective of this study was to determine whether vanillic acid has beneficial effects against dextran sulfate sodium (DSS)-induced ulcerative colitis. Our results showed that vanillic acid reduced the severity of the clinical signs of DSS-induced colitis, including weight loss and shortening of colon length, and the disease activity index. The results of this study showed that vanillic acid significantly suppressed the expression of cyclooxygenase-2 and the activation of transcription nuclear factor-κB p65 in DSS-treated colon tissues. In addition, we observed that the plasma levels of interleukin (IL)-6 were higher in the DSS-treated group than in the control group, but these increased levels were reduced by the administration of vanillic acid. Taken together, these findings suggest that vanillic acid has a beneficial effect on DSS-induced ulcerative colitis, thereby indicating its usefulness in the regulation of chronic intestinal inflammation.

Effect of Acanthopanax senticosus stem on mast cell-dependent anaphylaxis

We studied the effect of Acanthopanax senticosus stem (ACPS) on mast cell-dependent anaphylaxis. ACPS inhibited compound 48/80-induced systemic anaphylaxis at a dose of 1.0 g/kg by 50%. ACPS also inhibited passive cutaneous anaphylaxis reaction and histamine release from mast cells in a dose-dependent manner, respectively. Moreover, ACPS had an inhibitory effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha (TNF-alpha) production from mast cells. These results indicate that ACPS inhibits mast cell-mediated anaphylaxis in vivo and in vitro murine model.

The Protective Mechanism of Antioxidants in Cadmium-Induced Ototoxicity in Vitro and in Vivo

Background Several heavy metals have been shown to have toxic effects on the peripheral and central auditory system. Cadmium (Cd2+) is an environmental contaminant showing a variety of adverse effects. Given the current rate of release into the environment, the amount of Cd2+ present in the human body and the incidence of Cd2+-related diseases are expected to increase. Objective The overall aim of this study was to gain further insights into the mechanism of Cd2+-induced ototoxicity. Methods Cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), cytochrome c (cyt c), phosphorylated extracellular signal-regulated protein kinase (p-ERK), caspases, morphologic change, and functional changes in HEI-OC1 cells, rat cochlear explants, and mouse cochlea after Cd2+ exposure were measured by flow cytometry, immunohistochemical staining, Western blot analysis, and auditory brainstem response (ABR) recording. Mechanisms underlying Cd2+ototoxicity were studied using inhibitors of different signaling pathways, caspases, and antioxidants. Results Cd2+ exposure caused cell death, ROS generation, MMP loss, cyt c release, activation of caspases, ERK activation, apoptosis, and finally auditory threshold shift. Cd2+ toxicity interfered with inhibitors of cellular signaling pathways, such as ERK and c-jun N-terminal kinase, and with caspase inhibitors, especially inhibitors of caspase-9 and caspase-3. The antioxidants N-acetyl-l-cysteine and ebselen showed a significant protective effect on the Cd2+ toxicity. Conlcusions Cd2+ is ototoxic with a complex underlying mechanism. However, ROS generation may be the cause of the toxicity, and application of antioxidants can prevent the toxic effect.

Vanillic acid inhibits inflammatory mediators by suppressing NF-κB in lipopolysaccharide-stimulated mouse peritoneal macrophages

Vanillic acid is a benzoic acid derivative that is used as a flavoring agent. It is an oxidized form of vanillin. At present, the mechanisms by which vanillic acid exerts its anti-inflammatory effects are incompletely understood. In this study, we attempted to determine the effects of vanillic acid on lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. Our findings indicate that vanillic acid inhibits LPS-induced production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. During the inflammatory process, the levels of cyclooxygenase (COX)-2 and nitric oxide (NO) increased in mouse peritoneal macrophages, but vanillic acid suppressed both the enhanced levels of COX-2 and the production of prostaglandin E2 and NO. Moreover, vanillic acid suppressed the activation of nuclear factor-kappa B (NF-κB) and caspase-1. These results provide novel insights into the pharmacological actions of vanillic acid and are indicative of the potential use of this molecule in the treatment of inflammatory diseases.

Anti-inflammatory activity of chrysophanol through the suppression of NF-κB/caspase-1 activation in vitro and in vivo.

Chrysophanol is a member of the anthraquinone family and has multiple pharmacological effects, but the exact mechanism of the anti-inflammatory effects of chrysophanol has yet to be thoroughly elucidated. In this study, we attempted to determine the effects of chrysophanol on dextran sulfate sodium (DSS)-induced colitis and lipopolysaccharide (LPS)-induced inflammatory responses in mouse peritoneal macrophages. The findings of this study demonstrated that chrysophanol effectively attenuated overall clinical scores as well as various pathological markers of colitis. Additionally, chrysophanol inhibited the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and the expression of cyclooxygenase (COX)-2 levels induced by LPS. We showed that this anti-inflammatory effect of chrysophanol is through suppression of the activation of NF-kappaB and caspase-1 in LPS-stimulated macrophages. These results provide novel insights into the pharmacological actions of chrysophanol as a potential molecule for use in the treatment of inflammatory diseases.

Hypoxia-induced IL-6 production is associated with activation of MAP kinase, HIF-1, and NF-κB on HEI-OC1 cells

In the present study, we investigated the signal transduction pathways of expression of IL-6 in the desferrioxamine (DFX)-stimulated cochlear auditory cell line, HEI-OC1 cells. DFX increased the expression of HIF-1alpha and NF-kappaB in HEI-OC1 cells. DFX significantly increased the production of IL-6 (P<0.05) and expression of IL-6 mRNA but did not affect TNF-alpha production. DFX also induced the activation of mitogen-activated protein kinase (MAPK) including p38, ERK, and JNK on HEI-OC1. Increased IL-6 by DFX was significantly inhibited by p38 inhibitor, SB203580 (about 72% inhibition, P=0.027) but not ERK inhibitor, PD98059 or JNK inhibitor, SP600125. SB203580 inhibited the expression of IL-6 mRNA. Increased IL-6 production was partially inhibited by treatment of iron (HIF-1 inhibitor) or pyrriolidine-dithiocarbamate (PDTC, NF-kappaB inhibitor). DFX also induced IL-6 production and HIF-1alpha expression in the inner ear. We demonstrated the regulatory effects of MAPK, HIF-1alpha, and NF-kappaB on DFX-induced IL-6 production in a HEI-OC1 for the first time. In conclusion, these data indicate that regulation of inflammatory cytokine IL-6 by DFX, through mimicking hypoxic conditions, might explain its beneficial effect in the treatment of hypoxia-induced inner ear diseases.