• The Korean Journal of Physiology and Pharmacology
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• v.10 no.2
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• pp.101-108
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• 2006

The aim of the present study was to elucidate whether gallic acid could modulate the inflammatory allergic reaction and to study its mechanism of action Gallic acid inhibited compound 48/80- or immunoglobulin E (IgE)-induced histamine release from mast cells. The inhibitory effect of gallic acid on the histamine release was mediated by modulation of cAMP and intracellular calcium. Gallic acid decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated pro-inflammatory cytokine gene expression and production such as TNF- ${\alpha}$ and IL-6 in human mast cells, and the inhibitory effect of gallic acid was on dependent nuclear factor- ${\kappa}$B and p38 mitogen-activated protein kinase. Our findings provide evidence that gallic acid inhibits mast cell-derived inflammatory allergic reaction by blocking histamine release and pro-inflammatory cytokine expression.

• Natural Product Sciences
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• v.18 no.3
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• pp.183-189
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• 2012

It is well known that inflammation is associated with neurodegenerative disorders, including Alzheimer' disease, Parkinson's disease and ischemia. Nitric oxide (NO), a pro-inflammatory mediator, is produced by inducible NO synthase (iNOS) in microglia as well as macrophages and appears to account for neurodegeneration. In this study, we aimed to isolate NO inhibitors from Pyrus pyrifolia by activity guided purification. As a result, we identified daucosterol and ${\beta}$-sitosterol, which have not been isolated from this plant before. This article also describes NO inhibitory activities of the methanol extract of Pyrus pyrifolia fruit and the isolated compounds from this, which are lupeol, betulin, betulinic acid, ${\beta}$-sitosterol and daucosterol, in LPS-activated RAW 264.7 and BV2 cell lines. Western blot analysis was performed to clarify the underlying mechanism of NO inhibition in the two cell lines.

• Natural Product Sciences
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• v.18 no.3
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• pp.141-146
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• 2012

Veronica peregrina (Scrophylariaceae) has been widely used as a Korean traditional medicine for the treatment of various pathological conditions including infection, hemorrhage and gastric ulcer. In the current study, we investigated the inhibitory effect of methanolic extracts of V. Peregrina (VPM) on the LPS-mediated nitric oxide (NO) production in mouse (C57BL/6) peritoneal macrophages. NO production was significantly down-regulated by the treatment of VPM dose dependently. To evaluate the mechanism of the inhibitory action of VPM on NO production, we performed iNOS enzyme activity assay and checked the change of inducible nitric oxide synthase (iNOS) levels by Western blotting. Although VPM did not affect iNOS enzyme activity, iNOS protein expression was attenuated by VPM indicating VPM inhibits NO production via suppression of iNOS enzyme expression. In addition, VPM attenuated the expression of another pro-inflammatory mediator such as cyclooxygenase-2 (COX-2) in a dose dependent manner. We also found that VPM can reduce trypsin-induced paw edema in mice. Based on this study, we suggest that V. peregrina may be beneficial in diseases which related to macrophage-mediated inflammatory disorders.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.4
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• pp.281-288
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• 2001

Anticancer effect of methanol extract of Caesalpinia sappan L. on oral carcinoma (KB) and osteosarcoma (HOS) cells were investigated in this study. In order to elucidate the anticancer mechanism of Caesalpinia sappan L, we analyzed telomerase inhibitory effect of the methanol extract of Caesalpinia sappan L. In addition we prepared 5 fraction samples according to its polarity differences and analyzed anticancer effects on oral carcinoma and osteosarcoma cells. Following results are obtained in this study. 1. 50% cell proliferation inhibitory value ($IC_{50}$) of the methanol extract of Caesalpinia sappan L. against oral carcinoma (KB) cells and osteosarcoma (HOS) cells were $9.0{\mu}g/ml$ and $10.9{\mu}g/ml$, respectively. 2. The methanol extract of Caesalpinia sappan L. showed inhibitory effect of telomerase which is required for cancer cell immortality. Therefore, it seems that the anticancer effect of methanol extract of Caesalpinia sappan is at least partially due to telomerase inhibitory effect. 3. Five fraction samples were prepared according to its polarity and 88.7% of ingredient of total methanol extract was transferred to ethylacetate fraction. Thin layer chromatography analysis showed that dichloromethane fraction contained ingredient with relatively high polarity and ethylacetate fraction contained similar ingredient found in total methanol extract. 4. Anticancer effect was observed in n-hexane, dichloromethane, and ethylacetate fractions. The highest anticancer effect was found in dichloromethane fraction which had $IC_{50}$ value of 4.4 and $>4.0{\mu}g/ml$ against oral carcinoma (KB) cells and osteosarcoma (HOS) cells, respectively.

• Biomedical Science Letters
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• v.23 no.4
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• pp.310-320
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• 2017

Ginseng has been widely used for traditional medicine in eastern Asia and is known to have inhibitory effects on cardiovascular disease (CVD) such as thrombosis, atherosclerosis, and myocardial infarction. Because, platelet is a crucial mediator of CVD, many studies are focusing on inhibitory mechanism of platelet functions. Among platelet activating molecules, thromboxane $A_2$ ($TXA_2$) and P-selectin play a central role in CVD. $TXA_2$ leads to intracellular signaling cascades and P-selectin plays an important role in platelet-neutrophil and platelet-monocyte interactions leading to the inflammatory response. In this study, we investigated the inhibitory mechanisms of total saponin fraction from Korean red ginseng (KRG-TS) on $TXA_2$ production and P-selectin expression. Thrombin-elevated $TXA_2$ production and arachidonic acid release were decreased by KRG-TS dose (25 to $150{\mu}g/mL$)-dependently via down regulation of microsomal cyclooxygenase-1 (COX-1), $TXA_2$ synthase (TXAS) activity and dephosphorylation of cytosolic phospholipase $A_2$ ($cPLA_2$). In addition, KRG-TS suppressed thrombin-activated P-selectin expression, an indicator of granule release via dephosphorylation of mitogen-activated protein kinases (MAPK). Taken together, we revealed that KRG-TS is a beneficial novel compound inhibiting $TXA_2$ production and P-selectin expression, which may prevent platelet aggregation-mediated thrombotic disease.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.95-101
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• 2007

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a naturally occurring phytoallexin abundant in grapes and several plants, has been shown to be active in inhibiting proliferation and inducing apoptosis in several human cancer cell lines. On the line of the biological activity of resveratrol, a variety of resveratrol analogs were synthesized and evaluated for their growth inhibitory effects against several human cancer cell lines. In the present study, we found that one of the resveratrol analogs, 3,4,5-trimethoxy-4’-bromo-cis-stilbene, markedly suppressed human colon cancer cell proliferation (EC$_{50}$ = 0.01 ${\mu}$g/ml), and the inhibitory activity was superior to its corresponding trans-isomer (EC$_{50}$ = 1.6 ${\mu}$g/ml) and resveratrol (EC$_{50}$ = 18.7 ${\mu}$g/ml). Prompted by the strong growth inhibitory activity in cultured human colon cancer cells (Col2), we investigated its mechanism of action. 3,4,5-Trimethoxy-4’-bromo-cis-stilbene induced arrest of cell cycle progression at G2/M phase and increased at sub-G1 phase DNA contents of the cell cycle in a time- and dose-dependent manner. Colony formation was also inhibited in a dose-dependent manner, indicating the inhibitory activity of the compound on cell proliferation. Moreover, the morphological changes and condensation of the cellular DNA by the treatment of the compound were well correlated with the induction of apoptosis. These data suggest the potential of 3,4,5-trimethoxy-4’-bromo-cis-stilbene might serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and inducing apoptosis for the human colon cancer cells.

• Natural Product Sciences
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• v.10 no.6
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• pp.315-320
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• 2004

Alpha-viniferin was previously isolated as a cyclooxygenase (COX)-2 inhibitor from Carex humilis (Cyperaceae) and is an oligomeric stilbene compound with benzofuran (BF) moieties in its chemical structure. In the present study, a chemically synthetic BF compound, named as 3,3-dimethyl-2,3,4,6,7,8,9,10,11,12,13,14,15,16,17,18-hexadecahydro-1H-benzo[b] cyclopentadeca[d]furan-1-one, was discovered to inhibit bacterial lipo polysaccharide (LPS)-induced prostaglandin $E_2$ $(PGE_2)$ production in macrophages RAW 264.7. The BF compound exhibited a selectively preferred inhibitory effect on COX-2 activity over COX-1 activity. Furthermore, BF compound inhibited LPS-induced COX-2 expression at transcription level. As a down-regulatory mechanism of COX-2 expression shown by BF compound, suppression of nuclear factor $(NF)-{\kappa}B$ activation has been demonstrated. BF compound inhibited LPS-induced $NF-{\kappa}B$ transcriptional activity and nuclear translocation of $NF-{\kappa}B$ p65, in parallel, but did not affect LPS-induced degradation of inhibitory ${\kappa}B{\alpha}$ protein $(I{\kappa}B{\alpha})$. Taken together, anti-inflammatory effect of BF compound on $PGE_2$ production was ascribed by its down-regulatory action on LPS-induced COX-2 synthesis in addition to inhibitory action on enzyme activity of COX-2.

• Clinical and Experimental Reproductive Medicine
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• v.21 no.1
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• pp.99-110
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• 1994

One consequence of fertilization in mammals is an increased resistance of the zona pellucida (ZP) to proteases and various chemical reagents. This phenomenon has been called 'zona pellucida hardening' (ZPH), and it is generally accepted that it is caused by the secretory products of cortical granules released by the egg at fertilization. ZP of mouse oocytes maturing in vitro in a chemically defined medium becomes progressively more resistant to solubilization by chymotrypsin ("Spontaneous" ZP hardening). In the present study, it was aimed to find the specificity of spontaneous ZPH in relation to its possible relevance to the cortical reaction and the physiological block to polyspermy. When a maturation inhibitors, cAMP analog(dbcAMP) and phosphodiesterase inhibitor (IBMX) was added to culture medium, it prevent spontaneous ZPH of mouse oocyte during in vitro culture. Thus spontaneous ZPH requires GVBD, since it is prevented by those agents, which inhibit GVBD in vitro. However, culture for 3 hours in the presence of PMA(lOng/ml), a protein kinase C activator, resulted in ZPH without GVBD, thus suggesting that ZPH may be regulated independently apart from the event of GVBD. Pretreatment of mouse oocyte with FBS result in partially inhibitory effect on subsequent spontaneous ZPH. Induction of GVBD in vivo had a inhibitory effect on the spontaneous ZPH, but subsequent spontaneous ZPH. Induction of GVBD in vivo had a inhinbitory effect on the spontaneous ZPII, but had no inhibitory effect on PMA-induced ZPH. Treatment with a microfilament formation blocker(cytochalasin-B) at 1${\mu}g$/ml concentration, resulted in the excellent inhibitory effect on spontaneous ZPH. However cytochalasin-B did not inhibit PMA-induced ZPH. Thus this suggesting that spontaneuse ZPH had a different mechanism from PMA-induced ZPH.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.245-257
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• 1988

The present study was undertaken to investigate the effect of clonidine on the response of the dorsal horn cells to intra-arterially administered bradykinin $(BK:40{\mu}g)$ and $K^+(4mg)$ in spinal cats and cats with intact spinal cord. The change in the activities of low threshold (LT), high threshold (HT) and wide dynamic range (WDR) cells induced by BK and $K^+$ were determined before and after treatment of animals with clonidine. Also studied was mechanism of inhibitory action of clonidine on the responses of dorsal horn cells to the chemical algogenics. Number of WDR cell responded to intra-arterially administered BK and $K^+$ was greater in spinal animals than in cats with intact spinal cord. Following administration of BK or $K^+$ no change was observed in the activity of LT cell whereas activity of HT cell increased invariably. The increased response of HT cell to BK and $K^+$ was markedly suppressed by clonidine. On the other hand, such inhibitory actions of clonidine were almost completely blocked by yohimbine. The majority of WDR cells were activated by $K^+$ while response of WDR cells to BK was diverse (excitatory, inhibitory or mixed). These results indicate that clonidine inhibits responses of the dorsal horn cells not only to thermal or mechanical stimulations but also to chemical algogenics, and that the inhibitory action of clonidine is generally mediated through excitation of ${\alpha}_2-adrenoreceptors$.

• Journal of Acupuncture Research
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• v.15 no.2
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• pp.319-329
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• 1998

The purpose of this study was finding the pain inhibitory effect of acupuncture based on rataining time at LI -4. The pain at dentes incisor was evoked by noxious electric stimulation and digastric electromyogram(dEMG) changes based on time interval were measured. To do this, the opioid antagonist was administered intraperitoneally and four groups were made for convenience. Without naloxone, dEMG was changed by either retaining the needle for 40 minutes (Group I) or by lifting and thrusting the needle (Group II). With naloxone administration, dEMG was changed by either retaining the needle for 40 minutes (Group III) or by lifting and thrusting the needle (Group IV). The results are as following 1. The pain inhibitory effect of acupuncture at LI -4 was expressed best in Group I. 2. The pain inhibitory effect was somewhat expressed in Group II but the effect was smaller than Group I. 3 .In Groups III and IV, the pain inhibitory effect was not expressed. The overall result should be the foundation for the further studies to figure out the underlying mechanism of acupuncture. In addition, it is assumed that the results will be useful for optimal retaining time of acupucture for its maximal effect.