Hyung Min Kim

Dexamethasone Suppresses Tumor Necrosis Factor-α-Induced Apoptosis in Osteoblasts: Possible Role for Ceramide1

Ceramide has been proposed as a second messenger molecule implicated in a variety of biological processes, including apoptosis. Recently, it has been reported that tumor necrosis factor-α (TNF-α) activates the release of ceramide and that ceramide acts as a mediator for the TNF-α-induced stimulation of the binding affinity of nuclear factor-κB (NF-κB), a ubiquitous transcription factor of particular importance in immune and inflammatory responses. In this study we demonstrate that dexamethasone, which reduces the production of ceramide, significantly inhibits TNF-α-induced activation of NF-κB, c-Jun N-terminal kinase, also known as stress-activating protein kinase, caspase-3-like cysteine protease, redistribution of cytochrome c, and apoptosis in MC3T3E1 osteoblasts. Compared with TNF-α-induced JNK activation, ceramide elicits a more rapid activation of JNK within 30 min. C2-ceramide activates NF-κB and caspase-3 like protease to the same degree and with kinetics similar to those of TNF-α. This study prov...

Effects of Poncirus trifoliata on Type I Hypersensitivity Reaction

A study was carried out to examine the effect of an aqueous extract from immature fruit of Poncirus trifoliata L. (Rutaceae) (PTIFE) on the type I hypersensitivity reaction. Forty-eight hour PCA (passive cutaneous anaphylaxis) in rats was significantly inhibited by the oral administration of PTIFE (200 mg/kg). It also inhibited histamine release from rat peritoneal mast cells (RPMC) induced by mouse anti-dinitrophenyl (DNP)-IgE and dinitrophenyl-human serum albumin (DNP-HSA). These results suggest that PTIFE has anti-allergic action against the type I hypersensitivity reaction.

Radish extract stimulates motility of the intestine via the muscarinic receptors.

The effects of radish (Brassica oleraceae, Cruciferae) on gastrointestinal motility were examined using rat intestinal segments with myenteric plexus in‐vitro and measuring the intestinal transit of charcoal in‐vivo. Radish extract (10 μg mL−1 to 2 mg mL−1) caused a dose‐dependent increase in contractions of the duodenum, jejunum and ileum, and 1 mg mL−1 was the maximum effective dose. The largest contraction by the extract was found in ileal segments. The extract‐induced (0.5 mg ML−1) ileal contraction was remarkably inhibited by pretreatment of segments with atropine (10−7 M) for 10 min, but not by hexamethonium (0.5 mM). Moreover, antagonists of the muscarinic receptor reduced the radish‐induced ileal contraction by a different ratio. The rank order of inhibitory effects was 4‐diphenylacetoxy‐N‐methyl‐(2‐chloroethyl)‐piperidine methiodide (90.5% of control) > tropicamide (67.4%) > pirenzepine (42.8%) > methoctramine (16.7%). Oral administration of radish extract (300–500 mg kg−1 body weight) to mice remarkably improved the intestinal transit of charcoal, and this was significantly attenuated by co‐administration of atropine (50 mg kg−1). Taken together, these results suggest that radish extract stimulates gastrointestinal motility through activation of muscarinic pathways.

Effects of Siegesbeckia pubescens on Immediate Hypersensitivity Reaction

This study was carried out to examine the effect of an aqueous extract from Siegesbeckia pubescens (Compositae) (SPAE) on immunoglobulin E (IgE)-mediated immediate hypersensitivity reaction. Forty-eight hours passive cutaneous anaphylaxis in rats was significantly inhibited by oral administration of SPAE (100 micrograms/g). It also inhibited histamine release from rat peritoneal mast cells induced by anti-dinitrophenyl (DNP)-IgE and DNP-human serum albumin. The data indicate that SPAE has antiallergic activity, and that its action may be due to inhibition of histamine release from mast cells.

Effect of Alpinia oxyphylla Fruit Extract on Compound 48/80-induced Anaphylactic Reactions

The effect of the aqueous extract of Alpinia oxyphylla Miq. (Zingiberaceae) fruits (AOFE) on anaphylactic reaction was investigated. AOFE completely inhibited compound 48/80-induced systemic anaphylactic shock at dose of 1.0 g/kg. When AOFE was pretreated at concentrations ranging from 0.01 to 1.0 g/kg, the plasma histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. AOFE also inhibited the histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. The level of cAMP in RPMC, when AOFE was added, transiently and significantly increased about 4-fold compared with that of basal cells. These results indicate that AOFE may be beneficial in the treatment of non-specific anaphylactic reactions.

Szygium aromaticum (L.) Merr. Et Perry (Myrtaceae) flower bud induces apoptosis of p815 mastocytoma cell line

This study was conducted to investigate SAFB-induced apoptosis of mast cells as it pertains to both its basic drug mechanism and the potential therapeutics of the pathologic conditions accompanying mast cell proliferation. SAFB induced many apoptotic manifestations as evidenced by changes in cell morphology, generation of DNA fragmentation, activation of caspase 3, and DNA hypoploidy. The reduction of mitochondrial membrane potential and the release of cytochrome c to cytosol were also demonstrated. However, reduction of mitochondrial membrane potential and cytochrome c release were not prevented by caspase inhibitor zVAD-fmk or PTP blockers such as bongkrekic acid and cyclosporin A. Expression levels of Bcl-2 and Fas remained unchanged following SAFB treatment. This results suggest that the clinical effect of SAFB may depend on the pharmacological mechanism regulating the demise of mast cells.

The Evaluation of Antianaphylactic Effect of Oryza sativa L. in Rats

This study was carried out to examine the effect of methanol extract of Oryza sativa L. (Dong-Jin in Korean, abbreviate as Os-DJ hereafter) on anaphylaxis. Os-DJ (10(-5) to 1 g/kg) dose-dependently inhibited systemic anaphylaxis induced by compound 48/80 in rats. When Os-DJ was pretreated at concentration ranging from 10(-5) to 1 g/kg, the serum histamine levels were reduced in a dose-dependent manner. Os-DJ (1 g/kg) also significantly inhibited local anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. Moreover, Os-DJ dose-dependently inhibited the histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. These results indicate that Os-DJ possess antianaphylactic activity by inhibition of histamine release from mast cells in vivo and in vitro.

Shibimijihwang-tang elevates intracellular ATP and choline content in the cerebral cortex of ovariectomized rats.

Shibimijihwang-tang (SJT) has been used traditionally to improve systemic blood circulation and biological energy production in patients with circulatory and neuronal diseases. The object of this study is to determine the effect of SJT extract on the intracellular adenosine triphosphate (ATP) and choline content in the cerebral cortex of ovariectomized (OVX) rats. Bilateral ovaries of 8-week-old rats were removed. Rats were maintained for 12 weeks to deplete ovarian steroid hormones, followed by treatment with SJT at 500 mg/kg body weight per day for 12 weeks. High rate of body weight increase in the OVX rats was markedly reduced by treatment with SJT, but the change in body weight of normal rats was not affected by it. SJT also significantly reduced the decline of cerebral weight in the OVX rats (P<0.05). Tissue glucose content in the cerebral cortex of OVX rats was significantly increased by SJT treatment (P<0.05). A decline in cerebral ATP content in OVX rats was dramatically restored by SJT administration (P<0.01), but SJT did not change the cerebral ATP content in normal rats. Cerebral choline content also declined following ovariectomy. This reduction was significantly elevated by SJT treatment (P<0.05), but SJT did not affect the change in cerebral choline in normal rats. Taken together, these results demonstrate that SJT can reduce the decrease in brain weight, cerebral ATP and choline content caused by deprivation of ovarian steroid hormones. This suggests that pharmacological properties of SJT may play a role in improvement of reduced cerebral energy production and cholinergic neurotransmitter synthesis caused by deficiency of ovarian steroid hormones in the cerebroneuronal cells of postmenopausal women.

Synthesis and Analgesic Activity of Non-classical Bicyclic Cannabinoid Analogues

The synthesis of a series of non-classical bicyclic cannaboids is described. n n n n3-Phenylcyclohexanols were prepared in three steps from lithium diaryl cuprates. In preliminary tests (acetic acid-induced abdominal constriction and tail-flick tests), the compounds were found to have effective analgesic activity, comparable with δ1-tetra-hydrocannabinol. In the ring test for psychotrophic activity, the compounds exhibited no cannabis-type activity suggesting the separation of analgesic and psychotrophic activity. n n n nThese compounds represent a new class of potentially potent non-opiate analgesics.

Effect of glycyrrhetinic acid on histamine synthesis and release

The effect of glycyrrhetinic acid (18β-glycyrrhetinic acid, GA) on histarnine synthesis and release was investigated in cocultured mast cells with Swiss 3T3 fibroblasts. GA has strong dose dependent inhibitory activity for histamine synthesis and release in cocultured mast cells. GA (50 μM) inhibited about 85% of histidine decarboxylase (HDC) activity. The appearance of cells staining positively with berberine sulfate was also decreased in the presence of GA. It indicates that transdifferentiation of cultured mast cells (CMCs) was also inhibited.