• 대한핵의학회:학술대회논문집
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• 대한핵의학회 2001년도 제40차 춘계학술대회 및 연수교육
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• pp.66-75
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• 2001

Although diverse mechanisms are involved in multidrug resistance for chemotherapeutic drugs, the development of cellular P-glycoprotein(Pgp) and multidrug-resistance associated protein (MRP) are important factors in the chemotherapy failure to cancer. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However these methods do not yield information about dynamic function of Pgp and MRP un vivo. Single photon emission tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transport. $^{99m}Tc$-sestaMIBl and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of Pgp-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and N-$[^{11}C]$acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively in vivo. Results obtained from recent publications are reviewed to confirm the feasibility of using SPECT and PET to study the functionality of MDR transporters in vivo.

• Biomolecules & Therapeutics
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• 제22권3호
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• pp.193-199
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• 2014

The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin $D_2$ ($PGD_2$), leukotriene $C_4$ ($LTC_4$), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of $PGD_2$ and $LTC_4$ in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun $NH_2$-terminal kinase and p38), and the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.

• Tuberculosis and Respiratory Diseases
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• 제45권2호
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• pp.369-379
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• 1998

연구배경: Platelet-activating factor (PAF)는 염증반응의 중요한 매개체이며, 폐혈관의 투과성을 증가시키고, 급만성 폐동맥 고혈압을 유발하며 leukotriene의 합성을 촉진시킨다. 또한 PAF는 호중구의 화화주성, 응집, 탈과립 및 유착과 leukotriene $C_4$, $D_4$ 및 superoxide anion의 생산에도 영향을 미친다. PAF는 혈소판의 응집과 thromboxane $A_2$의 생산을 초래하여 혈액 응고를 촉진시키며 폐혈관계의 미소색전을 일으켜 폐 손상 발생의 주요원인 중 하나이다. 이와같은 현상은 PAF을 흡입후에도 유사한 반응들이 일어나는 것이 관찰된다. PAF는 급성 호흡곤란 증후군(acute respiratory distress syndrome, ARDS)의 병인에 중요한 매개체 중 하나로 알려져 있다. Surfactant는 폐 방어기전에 영향을 미치는데 첫째, surfactant protein-A(SP-A)와 대식세포간 상호작용이 적절한 대식세포 기능 유지에 중요하다. 둘째, surfactant는 수많은 염증에 관여되는 매개체들을 적절이 조정하며 셋째, surf actant 단백자체가 중요한 산화방지능이었으며 넷째, 호기시 폐포밖으로 외부에서 흡입된 각종 업자(불순물들을 제거한다. 이 중 어느하나에 장애가 오면 ARDS의 병인에 중요한 영향을 미친다. 방 법: PAF를 백서 기도내 투여후 surfactant단백 A, B 및 C의 mRNA 발현 양상을 filter hybridization방법으로 조사하여 surfactant단백 A, B 및 C 유전자 발현에 대한 PAF의 효과를 관찰하여 다음과 같은 결과를 얻었다. 결 과: SP-A mRNA양은 PAF투여군에서 대조군 및 Lyso-PAF투여군에 비하여 각각 37.1% 및 41.6% 유의하게 감소하였다 (p<0.025, p<0.01). SP-B mRNA양은 PAF투여군에서 대조군 및 Lyso-PAF 투여군에 비하여 각각 18.7% 및 32.2% 감소하였으나, 유의한 차는 없었다. SP-C mRNA양은 PAF투여군에서 대조군 및 Lyso-PAF투여군에 비하여 각각 30.7% 및 38.5% 유의하게 감소하였다(p<0.01, p<0.01). 결 론: 이상의 결과로 SP-A, B, C mRNA에 대한 PAF의 억제효과를 확인 하였으며 이와같은 surfactant단백들의 발현에 대한 PAF의 억제효과가 급성 호흡곤란증후군의 병인의 한요인으로 작용할 수 있을것으로 생각된다.

• Journal of Nutrition and Health
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• 제34권8호
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• pp.896-904
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• 2001

Conjugated linoleic acid(CLA) is a group of positional and geometric isomers of linoleic acid(LA) and exhibits anticarcinogenic activity in multiple experimental animal models. Cis-9,trns-11(c9t11) and trans-10,cis-12(t10c12) CLA are the principal isomers found in foods. The present study was performed to determine whether CLA and the two isomers inhibits HT-29 cell proliferation and to assess whether such an effect was related to changes in secretion of eicosanoids. Cells were incubated in serum-free medium with various concentrations(0 to 20$\mu$M) of CLA or LA. CLA inhibited cell proliferation in a dose-dependent manner, with maximal inhibition(70 $\pm$ 1%) observed at 20$\mu$M concentration after 96 hours. However, LA had no effect at the same concentration range. To compare the ability of c9f11 and t10c12 to inhibit cell proliferation, cells were incubated with increasing concentrations(0 to 4$\mu$M) of these isomers. T10c12 inhibited cell proliferation in a dose-dependent manner. A 66 $\pm$ 2% decrease in cell number was observed within 96 hours after addition of 4$\mu$M t10c12. By contrast, c9t11 had no effect. The concentrations of CLA and the two isomers in the plasma membrane were increased when they were added to the incubation medium. However, they did not alter the levels of arachidonic acid in plasma membrane. To assess whether the proliferation inhibiting effect of CLA was related to changes in eicosanoid production, prostaglandin E$_2$(PGE$_2$) and leukotriene B$_4$(LTB$_4$) concentrations in conditioned media were estimated by a competitive enzyme immunoassay. Both CLA and t10c12 increased the production of materials reactive to PGE$_2$ and LTB$_4$ antibodies in a dose-dependent manner. By contrast, c9t11 had no effect. These results indicate that inhibition of HT-29 cell proliferation by CLA is attributed to the effect of the t10v12 isomer. The materials reactive to PGE$_2$ and LTB$_4$ antibodies may inhibit growth stimulatory effect of arachidonic acid-derived eicosanoids on HT-29 cell proliferation.

• Biomolecules & Therapeutics
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• 제2권2호
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• pp.149-154
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• 1994

Anti-allergic and anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were evaluated in mice and rats. Several criteria were employed to assess the anti-allergic and anti-inflammatory actions of Cimicifuga heracleifolia, such as hyaluronidase activity, mediators-induced vascular permeability changes, 48 hour homologous passive cutaneous anaphylaxis (PCA) histamine release from mast cells, and the carrageenan-induced rat paw edema. To further characterize the active components, the water extract was either extracted with organic solvent or fractionated according to molecular weight, and each fraction was tested for some of anti-allergic parameters. Hyaluronidase activities, both in activating and in activated states, were significantly inhibited by the water extract of Cimicifuga heracleifolia and by some of its subfractions, molecular weight less than 1,000. The water extracts (50~400 mg/kg) significantly inhibited 48 hr homologous PCA and vascular permeability changes induced by chemical mediators (histamine, serotonin, and leukotriene $C_4$) in mice. In the case of histamine-induced vascular permeability changes, more extensive studies were conducted; water extract was either fractionated according to molecular weight or extracted with butanol. Anti-histamine actions were observed only from the water layer, and these active components were of the molecular weight less than 1,000. These anti-allergic actions were observed mainly from mice than from rats. On the other hand, anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were significant in rats.

• 한방재활의학과학회지
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• 제23권1호
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• pp.25-49
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• 2013

Objectives : This study was carried out to know the anti-osteroarthritic effects of Bangkibokryeong-tang(Fanjifuling-tang(BBT)) on the papain-induced osteoarthritis C57BL/10 mouse. Methods : Osteoarthritis was induced by injection of papain(6 ${\mu}l$) into knee joint of mouse. Osteoarthritic mice were divided into 4 groups(normal, control, joins(R), BBT). The injection did not fit the normal group. A week later, after the injection of papain, control group was taken normal saline 200 ${\mu}l$, positive control group was taken joins(R)(100 mg/kg), treated group was taken extract of Bangkibokryeong-tang(Fanjifuling-tang(BBT))(400 mg/kg). After then, we examined hepatotoxicity, nephrotoxicity, inflammation cytokines, expression of inflammation factor mRNA, hemotology, histology through the micro CT-arthrography, and etc. Results : 1. Hepatotoxicity and nephrotoxicity have not expressed. 2. The levels of IL-$1{\beta}$, TNF-${\alpha}$, IL-6, MCP-1, Thromboxane B2, Leukotriene B4, Prostaglandin E2 in serum were significantly decreased. 3. In hematology, the levels of neutrophils and monocytes were significantly decreased. 4. The expression of inflammation factor mRNA like TNF-${\alpha}$ and IL-6, COX-2, iNOS-II were significantly inhibited. 5. In micro CT-arthrography, cartilage volume was less decreased. 6. The degree of osteoarthritis induced damage of joint of BBT group is low in histopathologic observation(hematoxylin&eosin(H&E), Safranin-O). Conclusions : According to this study, BBT has effect of anti-osteoarthritis. Further clinical research for the cartilage protective effect is necessary.

• 대한화장품학회지
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• 제24권3호
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• pp.134-145
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• 1998

Facial hyperpigmentation in women, which is considered to be a serious cosmetic disability and a cause of mental distress, requires proper management. Melanocyte dendricity is a crucial factor affecting epidermal pigmentation. We found that BQ-788, the endothelin-B (ETB) receptor antagonist, blocks the formation of multi-dendricity which is induced by cocultured keratinocytes. Melanocytes in vivo show numerous dendrites which are in close contact with multiple keratinocytes, forming the epidermal-melanin unit. While melanocytes transfer their melanosomes into the neighboring keratinocytes via dendrites, keratinocytes secrete many growth factors and cytokines that influence viability, morphology, and melanin formation of melanocytes. Endothelin-1 (ET-1), prostaglandin E2(PGE2), and leukotriene-C4 (LT-C4) have been suggested as the candidates for increasing dendricity. Other reports suggested that ET-1 has stimulatory effects on proliferation and melanin formation of melanocytes in vitro. In the present study, using type-specific ET receptor antagonists, we observed how the morphology of melanocytes could be modulated in a coculture system. In addition, the roles of ET-1 for morphology and proliferation on melanocytes were evaluated in different culture media. We suggest that ET-1 increases dendricity and proliferation of melanocytes, and that its dendrite-inducing effect and mitogenic effect are regulated independently.

• Natural Product Sciences
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• 제17권2호
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• pp.90-94
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• 2011

An in vitro bioassay-guide revealed that the methanol (MeOH) extract of the whole plant of Patrinia saniculaefolia (Valerianaceae) showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2$ ($PGD_2$) and leukotriene $C_4$ ($LTC_4$) in mouse bone marrow-derived mast cells (BMMCs). Phytochemical study of the MeOH extract of this plant led to the isolation of twelve compounds; ${\beta}$-farnesene (1), squalene (2), nardostachin (3), patridoid I (4), patridoid II (5), patridoid II-A (6), oleanolic acid (7), oleanonic acid (8), 23-hydroxyursolic acid (9), oleanolic acid 3-O-${\alpha}$-L-arabinopyranoside (10), oleanolic acid 3-O-${\beta}$-D-glucopyranoside (11), oleanolic acid 3-O-[${\beta}$-D-xylopyranosyl-(1${\rightarrow}$3)-${\beta}$-D-(6-O-butyl)glucuronopyranoside] (12). Among the compounds, 4 and 5 strongly inhibited both the COX-2-dependent $PGD_2$ generation with $IC_{50}$ values of 8.7 and 13.6 ${\mu}M$, respectively, and the generation of $LTC_4$ in the 5-LOX dependent phase with $IC_{50}$ values of 41.7 and 46.9 ${\mu}M$, respectively, which suggest that the anti-inflammatory activity of P. saniculaefolia might occur in part via the inhibition of both $PGD_2$ and $LTC_4$ generation by 4 and 5.

• Archives of Pharmacal Research
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• 제29권8호
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• pp.617-623
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• 2006

In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2\;(PGD_2)$ and leukotriene $C_4\;(LTC_4)$ in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with ${\beta}-sitosterol$ (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was isolated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)- marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids.

• 동의생리병리학회지
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• 제25권3호
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• pp.438-444
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• 2011

Dojuk-San is known to be effective for treating a urinary diseases and stomatitis. However, its effects on the bone marrow-derived mast cell(BMMC) mediated allergy and inflammation mechanism remain unknown. In this study, the biological effects of Dojuk-San ethanol extract(DJS) were evaluated while focusing on its effects on the allergic mediator in phorbol 12-myristate 13-acetate(PMA) plus calcium ionophore A23187(A23187)-stimulated BMMCs. An investigation was also conducted to determine its effects on the production of several allergic mediators including interleukin-6(IL-6), prostaglandin D2($PGD_2$), leukotrieneC4(LTC4) and ${\beta}$-Hexosaminidase(${\beta}$-Hex). The results revealed that DJS inhibited the PMA plus A23187 induced production of IL-6, PGD2, LTC4 and ${\beta}$-Hex. Taken together, these findings indicate that DJS has the potential using in the treatment of allergy.