• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.887-892
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• 2004

Cheonggeumganghwa-tang(CGT) has been used for the purpose of prevention and treatment of bronchial asthma and allergic asthma in Korea. To investigate the biological effect of CGT, the author examined cytotoxicity and inflammatory cytokines secretion with human mast cell line, HMC-1. HMC-1 was stimulated with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. CGT by itself had no effect on viability of HMC-1. The effects of CGT on the secretion of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 from HMC-1 were evaluated with enzyme-linked immunosorbent assay (ELISA). CGT (1 ㎎/㎖) inhibited PMA plus A23187 -induced TNF-α and IL-6 secretion, by 93.86 ± 2.05%, 68.69 ± 2.86%, respectively. CGT also inhibited the NF-κB (p50) expression. Taken together, these results suggest that CGT inhibit the production of inflammatory cytokines in HMC-1 cells through blockade of NF-κB activation.

• The Korean Journal of Physiology
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• v.29 no.2
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• pp.243-250
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• 1995

A possible potentiation between cholecystokinin (CCK) and secretin in amylase secretion from isolated rat pancreatic acini was investigated. Combined treatment of acini with secretin and CCK at low concentrations, which are known to be physiological, resulted in enzyme secretion larger than the arithmetic sum of their separate effects. Such a potentiating effect also occurred between secretin and A23187 (Ca ionophore), between forskolin (adenylate cyclase activator) and CCK, and between forskolin and A23187. Staurosporin (protein kinase C inhibitor) and W7 (calmodulin antagonist) inhibited markedly the potentiated amylase release induced by the agonists, but KT5720 (protein kinase A inhibitor) did not affect the potentiated amylase release. Therefore, we concluded that the action of CCK in a physiological concentration is potentiated by secretin in a physiological concentration range and vice versa, and that the intracellular mechanism necessary for the potentiation is associated with $Ca^{2+}$. However, it is uncertain what mechanisms are involved in potentiation of amylase release after CAMP and $Ca^{2+}$.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.107-115
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• 1997

We studied the effects of bile acids on the induction ofapoptosis in HepG2 human hepatocellular carcinoma cells. Treatment with either ursodeoxycholic acid (UDCA) or lithocholic acid (LCA) resulted in a dose- and time-dependent decrease in cell viability assessed by MTT assay. Both UDCA and LCA also induced genomic DNA fragmentation, a hallmark of apoptosis, indicating that the mechanism by which these bile acids induce cell death was through apoptosis. Cycloheximide, a protein synthesis inhibitor, blocked the apoptosis induced by these bile acids, implying that new protein synthesis may be required for the apoptosis. Intracellular $Ca^{2+}$ release blockers (dantrolene and 3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester) inhibited decreased cell viability and DNA fragmentation induced by these bile acids. Treatment of HepG2 cells with calcium ionophore A23l87 induced DNA fragmentation. These results suggest that UDCA and LCA induce apoptosis in the HepG2 cells and that the activation of intracellular $Ca^{2+}$ signals may play an important role in the apoptosis induced by these bile acids.

• Advances in Traditional Medicine
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• v.5 no.1
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• pp.69-74
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• 2005

'SecSec' has been used for the purpose of prevention and treatment of throat diseases such as sore throat, cough, bronchial asthma and allergic asthma in Korea. However, its effect in experimental models remains unknown. To investigate the biological effect of SecSec, we examined cytotoxicity and secretion of inflammatory cytokines on human leukemic mast cell line, HMC-1, stimulated with phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187. SecSec by itself had no cytotoxicity on HMC-1. When SecSec (1 mg/ml) was added, the secretion of tumor necrosis factor-alpha $(TNF-{\alpha})$, interleukin (IL)-6, and granulocyte macrophage-colony stimulating factor (GM-CSF) was significantly inhibited about 47.20%, 25.55%, and 46.43%, respectively on PMA plus A23187-stimulated HMC-1 cells. But SecSec did not inhibit IL-8 secretion. These findings may help understanding the mechanism of action of this medicine leading to control activated mast cells on allergic inflammatory condition like asthma.

• BMB Reports
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• v.29 no.1
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• pp.11-16
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• 1996

The present study showed that receptor-mediated activation of rabbit kidney proximal tubule cells by angiotensin II, the $Ca^{2+}$ ionophore A23187, or the protein kinase C activator phorbol myristate acetate (PMA) all stimulated phospholipase D (PLD). This was demonstrated by the increased formation of phosphatidic acid, and in the presence of 0.5% ethanol, phosphatidylethanol (PEt) accumulation. Angiotensin II leads to a rapid increase in phosphatidic acid and diacylglycerol, and phosphatidic acid formation preceeded the formation of diacylglycerol. This result suggests that some phosphatidic acid seems to be formed directly from phosphatidylcholine hydrolyzed by Pill. On the other hand, EGTA substantially attenuated angiotensin II and A23187-induced PEt formation, and when the cells were pretreated with verapamil angiotensin II-induced Pill activation was completely abolished. These results provide the evidence that calcium ion influx is essential for the agonist-induced Pill activation. In addition, staurosporine, an inhibitor of protein kinase C, strongly inhibited PMA-induced PEt formation, but was ineffective on angiotensin II-induced PEt accumulation. $GTP{\gamma}S$ also stimulates PEt formation in digitonin-permeabilized cells, but pretreatment of the cells with pertussis toxin failed to suppress angiotensin II-induced PEt formation. From these results, we conclude that in the rabbit kidney proximal tubule cells the mechanisms of angiotensin II- and PMA-induced Pill activation are different from each other and mediated via a pertussis toxin-insensitive trimeric G protein.

• Biomedical Science Letters
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• v.26 no.3
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• pp.192-200
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• 2020

Natural products have received revived interest via traditional remedies or alternative medicine used for the treatment of various diseases. Zanthoxylum piperitum (ZP) has been utilized in traditional medicine for various medicinal purposes. The present study was conducted to evaluate whether ZP modulates allergic inflammation both in vivo and in vitro. We examined the pharmacological effects of ZP on 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) symptoms in mice. Additionally, in order to clarify the anti-inflammatory mechanisms of ZP, we elucidate the effect of ZP on the expression levels of inflammatory cytokines and nuclear factor-κB (NF-κB) in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The results demonstrated that ZP attenuated AD clinical symptoms such as erythema, edema and dryness as well as histamine and IgE serum levels in DNCB-induced AD model mice. Additionally, ZP suppressed the expression of inflammatory cytokines and activation of NF-κB in AD-like skin lesions and stimulated HMC-1. These results provide experimental evidence that ZP may be useful candidate for treating allergic inflammation including AD.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.233-237
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• 2009

Lindera obtusiloba has been used for centuries as a traditional medicine in Korea and recently known to have an anti-fibrotic effect. In this report, we investigated the effect of hot water extract from L. obtusiloba (WELB) on the mast cell-mediated allergic inflammation and studied its possible mechanisms of action. WELB inhibited phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced histamine release in HMC-1 human mast cells. WELB reduced PMACI-induced gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-$\alpha$, interleukin (IL)-$1{\beta}$, IL-6, and IL-8. The inhibitory effect of WELB on the expression of proinflammatory cytokines was c-jun N-terminal kinase and nuclear factor-${\kappa}B$ dependent. These results indicate that WELB may be beneficial in the treatment of mast cell-mediated allergic inflammation.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.188-191
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• 1995

The Present study was undertaken to indicate the major source of NO by liver cells in vitro. Even at early stages of induction or low LPS concentrations, NO was produced at high rates by LPS(Lipopolysaccharide) on the isolated rat kupffer cells. PMA(phorbol 12-myristate 13-acetate) induced NO formation at low rates in the same cells. IFN-${\gamma}$ (Interferon-${\gamma}$) alone had not induced NO formation but it stimulated the effects of LPS. Calcium ionophore A23187 caused no stimulatory effect. It suggests that LPS has especially strong NO inducer on the kupffer cells and its mechanism is related to those on macrophage in other organs. In other nonparenchymal liver cells, sinusoidal endothelial cells were not stimulated to produce NO either by inducers of aortic endothelium(A23187, ATP and ADP) or by effectors of macrophages(LPS, IFN-${\gamma}$. This results suggest that rat liver kupffer cells appear to be the major source of NO by liver cells in vitro. But in vivo, liver endothelial cells may still be capable of producing NO. Furthermore, kupffer cells may produce factors that facilitate NO production by the endothelial cells.

• Natural Product Sciences
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• v.16 no.3
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• pp.185-191
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• 2010

Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In the present study, the effect of water extract of Gleditsiae Spina (WGS) (Leguminosae), on compound 48/80-induced systemic allergic reaction, anti-DNP IgE antibody-induced local allergic reaction, and histamine release from human mast cell line (HMC-1) cells were studied. In addition, the effect of WGS on phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-induced gene expression and secretion of pro-inflammatory cytokines were investigated using HMC-1 cells. WGS was anally administered to mice for high and fast absorption. WGS inhibited compound 48/80-induced systemic allergic reaction. WGS dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis. WGS reduced histamine release from HMC-1 cells. In addition, WGS decreased the gene expression and secretion of pro-inflammatory cytokines in PMA plus A23187-stimulated HMC-1 cells. These findings provide evidence that WGS could be a candidate as an antiallergic agent.

• Journal of Embryo Transfer
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• v.16 no.1
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• pp.1-5
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• 2001

A total of 92 unfertilized human oocytes were treated with ethanol (EtOH), calcium ionophore A23187 (CI) or electric pulse (EP) for activating pronuclear formation and subsequent development. In Experiment 1, there was a significant (P=0.0001) treatment effect on the activation of unfertilized oocytes. No spontaneous activation was occurred in the control, but activation treatments induced PN formation with various efficacy. More unfertilized oocytes (UFOs) were activated after EtOH or EP treatment than after CI treatment. EP was as effective (63.6 %) as EtOH, but fragmentation was observed in 43% of UFOs activated by EP. Proportion of UFOs that formed presumptive haploid PN (2 PNs+1 PB or 1 PN +2 PBs) was 33.3, 0 and 28.6% after EtOH, CI and EP treatments, respectively. In Experiment 2, a significant (P=0.0362) effect of immature oocytes (IOs) status on activation was fecund. IOs at the GVBD-MI oocytes had higher potential to form PN than those at the GV stage or with abnormal morphology (25 vs. 77.8%). The results of this study clearly demonstrated that the treatment of 10% ethanol for 5 min effectively induced the activation of UFOs. IOs could form pronucleus with high efficacy by ethanol treatment, as long as they grew beyond the GVBD stage.