• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.53-53
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• 1993

In considering the mechanism of action of the calcium antagonists, it is important to realize that there are three distinct receptor types and that the new classification divides these three drugs as members of the dihydropyridine, phenylalkylamines and benzothiazipines, respectively. The World Health Organization as well as the International Union of Pharmacology and Cardiology have adopted this classification. Unlike every other class of drugs, such as the alpha and beta adrenergic blocking agents, diuretics, etc., the calcium antagonists need to be thought of as three distinct drug classes. The reason they share some, but not all of the pharmacological profile is that they all act at specific receptor domains present in one large protein of 165 daltons present in all excitable tissue. This protein along with several other subunits make up what is known as the voltage-dependent calcium channel (the so-called "L"type, L-VDCC). The mechanism of action of the three drugs involve first a specfic binding and then an inhibition of the movement of calcium into the cell Some of these drugs, such as diltiazem, may have other interesting intracellular effects perhaps associated with protection of the mitochondria during ischemic insults. The nature of the receptor is being explored by molecular genetic techniques, and we have recently cloned two of the major subunits; some of the data will be presented.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2020년도 춘계학술대회
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• pp.89-89
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• 2020

In this study, we evaluated the effect of the extracts from Lonicera caerulea leaves (LCLE), branches (LCBE) and fruits (LCFE) on the cell growth and migration in human colorectal cancer cells, HCT116 and SW480 cells. LCLE and LCBE dose- and time-dependently inhibited the proliferation of HCT116 and SW480 cells. However, LCFE did not affect the proliferation of HCT116 and SW480 cells. In addition, LCLE and LCBE dramatically cell migration and wound healing in HCT116 cells. LCLE and LCBE decreased β-catenin protein level but not mRNA level in HCT116 and SW480 cells. Furthermore, LCLE decreased TCF4 level in both protein and mRNA level in HCT116 and SW480 cells. However, LCBE decreased TCF4 protein level but not mRNA level in HCT116 and SW480 cells. Based on these findings, LCLE and LCBE may inhibit the cell proliferation and migration through blocking Wnt signaling activation in human colorectal cancer cells. Therefore, LCLE and LCBE may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

• Journal of Pharmaceutical Investigation
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• 제27권1호
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• pp.57-64
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• 1997

$Amino-{\beta}-lactam$ antibiotics are absorbed by the dipeptide transporter in the small intestine. These uptakes are coupled to a proton influx. The inward proton gradient is partly induced by the $Na^+/H^+$ exchanger and calcium ion is involved in control of this antiport. Interaction between ampicillin which is one of the $Amino-{\beta}-lactam$ antibiotics and nifedipine which is one of calcium channel blocking agents was studied in rats in vivo and with rabbit jejunum mounted on the Sweetana/Grass diffusion cells in vitro. Bioavailability of ampicillin was increased significantly when nifedipine was co-administered orally in rats. There were no differences in the distribution phase and the elimination phase when ampicillin was given either alone or with nifedipine intravenously. Conditions for in vitro experiments were determined. The lift rate of $O_2/CO_2$ gas was controlled to 3 bubbles/sec and ampicillin was stable in the Kreb's buffer at pH 6.0. Absorption of ampicillin was the greatest when the completely-stripped serosal membrane was used. Transport of ampicillin from mucosal to serosal side in the rabbit jejunum was enhanced by 32% in the presence of nifedipine (p=0.059). Above results suggest that nifedipine might increase the plasma level of ampicillin via the improved absorption in the intestine rather than the reduction in the elimination or/and alteration in the distribution.

• KSBB Journal
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• 제16권5호
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• pp.486-492
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• 2001

숙지황 물추출물로부터 분리된 fraction(RG-III) 의 항돌연변이원성의 기작을 E. coli GW, B/r 균주를 이용하여 조사하였다. SOS 유도를 반영하는 $\beta$-galactiosidase 활성이 E. coli GW 1060, 1103, 1107, 1105에서 증가되지 않았다. RG-III는 RecA는 단백질의 합성을 증폭시키거나 LexA 산물의 분해를 저해하지 않았으므로 SOS en 기능의 발현이 영향을 미치지 못했다. 따라서 DNA 수복의 경로가 다른 E. coli B.r 변이주를 사용하여 4NQO와 MNNG에 대한 세포내 항돌연변이원성과 생존효과를 조사하였다. ZA159(uvrB, 최)를 제외한 WP2, WP2s, WP67, CM561, CM611에서 RG-III는 4NQO에 대한 생존력을 미약하게나마 증가시켰으나, 이러한 생존력 재활성을 수복모드에 의해 설명할 수 없었다. WP2, WP2s, WP67, CM561, CM611에서 RG-III는 MNNG로 유도된 돌연변이원성과 치사력을 증가시킴에도 불구하고 ZA159(uvr B, chl)에서는 감소시켰다. 4NQO의 변이원성을 두드러지게 억제하였으나 ZA159(uvr B, chl)에서 상승효과가 상대적으로 감소되었다. 이러한 결과들은 RG-III가 4NQO의 변이원성을 방어하는 차단제임을 시시하여, chl 산물의 기능과 유사한 작용을 하는 것으로 사료된다.

• 한국자원식물학회지
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• 제31권2호
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• pp.117-123
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• 2018

비지는 대두 가공 시 생산되는 부산물로 대부분 폐기되고 있는 실정이지만, 최근 비지를 유용한 자원으로 이용하기 위한 기능성 연구가 진행되고 있다. 그러나 비지의 항염증에 대한 연구가 미비하여 본 연구진은 비지추출물이 마우스 대식세포인 RAW264.7에 LPS에 의한 염증 반응에 미치는 영향을 평가하였다. 본 연구에서 비지추출물은 NF-${\kappa}B$와 p38의 활성 억제를 통해 만성염증 유발인자인 NO, iNOS, $PGE_2$, COX-2, TNF-${\alpha}$ 및 IL-$1{\beta}$의 발현을 억제하는 것으로 확인되었다. 따라서 비지는 독성과 부작용이 적은 항염증 관련 식의약 소재로 활용될 수 있을 것으로 사료된다.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.96-96
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• 2018

Although the roots of Heracleum moellendorffii (HM-R) have been long treated for inflammatory human diseases, scientific evidence for the anti-inflammatory activity of HM-R is not sufficient. In this study, we investigated anti-inflammatory activity and mechanism of action of HM-R in LPS-stimulated RAW264.7 cells. HM-R blocked LPS-induced NO and PGE2 production, but not HM-L. HM-R inhibited LPS-induced overexpression of iNOS, COX-2, $IL-1{\beta}$ and IL-6 in RAW264.7 cells. HM-R inhibited LPS-induced $NF-{\kappa}B$ signaling activation through blocking $I{\kappa}B-{\alpha}$ degradation and p65 nuclear accumulation. In addition, HM-R inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, HM-R inhibited attenuated LPS-mediated overexpression of the osteoclast-specific factors such as NFATc1, cathepsin K, MCP-1 and TRAP. These results indicate that HM-R may exert anti-inflammatory activity by inhibiting $NF-{\kappa}B$ and MAPK signaling activation. From these findings, HM-R has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammation and inflammatory diseases.

• 한국자원식물학회지
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• 제33권4호
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• pp.263-270
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• 2020

이상의 연구 결과로 미루어 볼 때, 댕댕이나무 잎과 가지 추추출물은 대장암 세포주 HCT116과 SW480세포의 생육을 억제하였으나 열매추출물은 억제활성이 나타나지 않았다. 잎과 가지 추출물은 cell migration과 wound healing assay를 통해 비정상적인 세포증식 억제를 확인하였으며, β-catenin과 TCF4의 단백질 수준을 감소시켜 비정상적인 Wnt 신호전달을 억제를 통해 대장암세포의 생육을 억제하는 것으로 판단된다. 따라서 댕댕이나무 잎과 가지는 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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• pp.67-67
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• 2019

Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of ${\alpha}$-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced $NF-{\kappa}B$ signaling activation through blocking $I{\kappa}B-{\alpha}$ degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

• 대한의생명과학회지
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• 제20권4호
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• pp.250-255
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• 2014

Mycobacterium tuberculosis (MTB) resides and replicates inside macrophages. In our previous report, we reported that CD8+ T cell-mediated immune responses specific for the peptide derived from MTB RNA polymerase beta-subunit ($RpoB_{127-135}$) could be induced in TB patients expressing HLA-$A^*0201$ subtype. In order to examine whether $RpoB_{127-135}$ specific CD8+ T cells can recognize MTB infected macrophages in vitro, CD8+ T cell lines specific for $RpoB_{127-135}$ peptide were generated from peripheral blood mononuclear cells (PBMCs) of healthy HLA-$A^*0201$ subjects by in vitro immunization technique. In this study, we observed $RpoB_{127-135}$ specific CD8+ T cells could recognize and destroy macrophages infected with MTB for 2 to 4 days. $RpoB_{127-135}$ specific CD8+ T cell immune response was inducible from PBMC of healthy subjects expressing HLA-$A^*0206$ subtype, one of HLA-A2 supertype members. Next, we investigated the HLA-I processing mechanism of $RpoB_{127-135}$ peptide in MTB infected macrophages. As a result, the presentation of the MTB derived epitope peptide, $RpoB_{127-135}$, to CD8+ T cells was not inhibited by the treatment with brefeldin-A (ER-Golgi transport inhibitor) or lactacystin (proteasome inhibitor), which blocks the classical HLA-I processing pathway. However, $RpoB_{127-135}$ specific CD8+ T cell activity was blocked either by the blocking agent for the endocytosis (cytochalasin D) or by the blocking antibody (W6/32) for HLA-I molecules. Therefore, the $RpoB_{127-135}$ peptide may be processed by accessing the alternate HLA-I processing pathway. Understanding the processing and presentation mechanisms of the MTB derived proteins will help to improve the efficacy of vaccines and the efficiency of therapeutic agents for TB.

• 대한약리학회지
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• 제2권1호
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• pp.21-29
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• 1966

Dichloroisoproterenol(DCI) i; one of the well known ${\beta}$-adrenergic receptor blocking agents. According to Moran and Perkins, DCI has sympathomimetic like action in relatively low concentrations. Fleming and Hawkins confirmed that DCI acts upon the receptors concerned with positive chronotropic and inotropic actions in the heart. Vogins reported that DCI, in concentration of $5{\times}10^{-8}$ to $5{\times}10^{-6}g/ml$, had properties of sympathomimetic amine causing positive inotropic and chronotropic actions in normal rat atria. And James and Nadeau found that DCI had not only adrenergic blocking effect in moderate and higher concentrations, but it also blocked the effect on the sinus node by vagal stimulation and of directly administered acetylcholine in higher concentrations. As stated above by many authors, DCI has complicated actions according to its concentrations. Our aim at the present experiments was to study the effects of DCI to the action of ouabain and acetylcholine upon the excised rabbit atria, as well as to the action of barium chloride and acetylcholine upon the excised rabbit intestine. In addition, Pan ax Ginseng is widely used as tonics in oriental nations, its pharmacological action, however, has not been clearly established. So we atempted to investigate the effects of the water extract of Panax Ginseng to the action of ouabain and DCI upon both atria and intestine. The results obtained were as follows. 1) DCI has a negative inotropic effect on the excised rabbit atria at concentration of $10^{-5}$ and a positive inotropic effect at concentration of $10^{-6}$. 2) DCI (at concentration of $10^{-6}$) potentiates the positive inotropic effect of ouabain upon the excised rabbit atria. 3) DCI antagonizes the action of acetylcholine upon the excised rabbit atria. 4) The water extract of Panax Ginseng, at concentration of $10^{-3}$, decreases the contractile force of rabbit atria, and tends to slightly increase that of rabbit atria at $10^{-4}$. 5) The water extract of Panax Ginseng exhibits a synergistic action with ouabain on the contractile force of rabbit atria. 6) DCI, in concentrations of $10^{-7}{\sim}10^{-6}$, depresses the tone and amplitude of contraction of the excised rabbit intestine. The depression of the intestinal tone markedly appears in pretreatment with reserpine 2mg/kg 24 hours. 7) DCI antagonizes the contractile effect of barium chloride on the excised rabbit atria. 8) DCI has no significant influence on the action of acetylcholine upon the excised rabbit intestine. 9) The series of those evidences indicates that DCI has a sympathomimetic-like action and more over a relaxing action directly on the excised rabbit intestine. 10) The water extract of Panax Ginseng in concentrations of $10^{-4}{\sim}10^{-3}$, has transient depression of the intestinal tone, but later gradually recovers its normal motility: 11) The water extract of Panax Ginseng has a synergistic action with ouabain on the intestinal contractility.