• 대한한의학회지
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• 제27권3호
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• pp.107-131
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• 2006

Background and Aims: Dansamtongmek-tang (DSTMT) and Dansamsengmek-san (DSSMS) have been used for many years as therapeutic agents for the acute stage of cerebrovascular disease, hypertension and hyperlipidemia in Oriental medicine, but the effects of DSTMT and DSSMS on hyperlipidemia and safety for cell damage are not yet well-known. This study was done to investigate the effects of DSTMT and DSSMS on hyperlipidemia. Methods: In vivo test: after administering DSTMT and DSSMS to SHR and ICR occurred hyperlipidemia for 3 weeks, we analyzed body weight, cholesterol levels. TG, HDL-chol, LDL-chol, LDH in plasma, brain, liver and kidney tissue, and DNA by RT-PCR. In vitro test: after administering DSTMT and DSSMS to human hepatocellular carcinoma in hypoxia, we observed cell cohesion by light microscope, analyzed the inflow of Ca2+ by confocal laser scanning microscope and DNA by RT-PCR. Results: DSTMT significantly decreased the levels of triglyceride and increased the levels of HDL-cholesterol in SHR, and significantly decreased the levels of LDL-cholesterol and body weight and increased the levels of HDL-cholesterol in ICR. DSSMS significantly decreased body weight, total cholesterol levels, LDL-cholesterol, LDH and cardiac risk factor (CRE) in SHR and significantly decreased the levels of total cholesterol, triglyceride, LDL-cholesterol, LDH and CRF in ICR. DSTMT had an effect on protecting cells from damage by inhibiting production of p53 mRNA, and in DSSMS, by inhibiting production of p53 mRNA and p21 mRNA after hypoxia. DSTMT effectively blocked off Ca2+ at low density, but DSSMS effectively blocked off Ca2+ at high density. Both DSTMT and DSSMS had an effect on inhibiting lipid metabolism by blocking off production of apo B mRNA. Conclusions: These results suggest that DSTMT and DSSMS might be usefully applied for treatment of hyperlipidemia and suppression of brain damage.

• 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.3-6
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• 2001

Inflammation is an outcome or an end effect of disruption of complex immunological balance. A variety of approaches to control immunological unbalance have been tried, and some of them are in practice in the clinic. Since inflammatory disorders are reflection of very complex immunological responses, it should be difficult to have such disorders under complete control. Thus, most of the drugs, being marketed and under development, possess some degrees of undesired side offsets originating from disruption of immunological balance. Steroids are excellent drugs suppressing inflammation in short term, however, long-term use of steroids would incur a serious side effect of "rebound". Another example is TNF-${\alpha}$-neutralizing agents, such as enbrel and infliximab. TNF-${\alpha}$ has been known to play a key role in the exacerbation of inflammation, and knock-out of TNF-${\alpha}$ is regarded essential to control of chronic inflammation. The TNF-${\alpha}$-neutralizing drugs in the market are regarded very efficient in the management of rheumatoid arthritis. Upon long term use, however, those drugs cause sepsis to a certain proportion of patients. It is ironical that a high plasma level of TNF-${\alpha}$ is known to be responsible for sepsis, and that the drugs scavenging TNF-${\alpha}$ cause sepsis. The above two examples illustrate well the difficulty of discovering an anti-inflammatory drug without unwanted immunological side effects. An anti-inflammatory drug would make a case in the market, as long as the drug has huge therapeutic benefits compared to its expected but unwanted immunological side effects, where cyclooxygenase-2 inhibitors are positioning. In this presentation, will be discussed general aspects of cyclooxygenase-2 inhibition in conjunction with 3(2Η)furanone derivatives, a novel class of COX-2 inhibitors.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7363-7369
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• 2014

The present study aimed to prepare and evaluate polymeric micelles conjugated with folic acid through ${\alpha}$- or ${\gamma}$-carboxyl groups for antitumor efficacy. The isomeric block copolymers, ${\alpha}$- and ${\gamma}$-folate-polyethyleneglycol-distearoyl phosphatidylethanolamine (${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE), were produced by solid phase peptide synthesis. Three types of doxorubicin (DOX)-loaded polymeric micelles (MPEG-DSPE-DOX and ${\alpha}$- / ${\gamma}$-Fol-PEG-DSPEDOX micelles) were prepared via the film formation method. Compared with MPEG-DSPE-DOX micelles, the ${\alpha}$- / ${\gamma}$-Fol-PEG-DSPE-DOX micelles presented a higher cellular uptake behavior in the live cell study. Cell viability percentages were 81.8%, 57.3%, 56.6% at 2 hours for MPEG-DSPE-DOX, ${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE-DOX micelles, respectively (p<0.05). Using the KB xenograft tumor model, both ${\alpha}$- and ${\gamma}$-folate-conjugated micelles were found to have better antitumor effects with lower toxicity in comparison with MPEG-DSPE-DOX micelles. No difference in in vivo antitumor efficacy was found between ${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE-DOX micelles. The folate-conjugated micelles might be a potentially useful strategy for tumor targeting of therapeutic agents, whether grafting with folic acid through ${\alpha}$- or ${\gamma}$-carboxyl groups.

• 한국자원식물학회지
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• 제27권5호
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• pp.439-446
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• 2014

본 연구는 구실잣밤나무(C. cuspidate) 잎 추출물의 항염증 활성이 염증성 매개인자 생성 저해 및 염증성 사이토카인의 억제와 관련이 있을 것으로 예상되어짐에 따라, 구실잣밤나무를 대상으로 80% 에탄올를 가지고 추출한 후 추출물을 극성에 따라 순차적으로 용매분획을 실시하여, 구실잣밤나무 80% 에탄올 추출물 및 용매분획물들이 염증반응의 주체가 되는 대식세포 계열인 RAW 264.7 세포에서 LPS로 유도된 NO의 생성억제효과, 그리고 iNOS와 COX-2의 mRNA와 단백질 발현 억제효과 및 IL-6와 IL-$1{\beta}$와 같은 염증성 사이토카인 생성 억제효과 등을 알아보았다. 대식세포 계열인 RAW 264.7 세포에 LPS로 자극을 주고 구실잣밤나무 80% 에탄올 추출물 및 분획물을 처리하여 확인해본 결과, 헥산, 디클로로메탄 및 에틸아세테이트 분획물에서 NO의 생성억제 효과가 강하게 나타났으며, 헥산과 디클로로메탄 분획물에서는 iNOS와 COX-2 생성 억제 효과가 다른 분획물에 비해 강하게 나타났으며 염증성 사이토카인 생성 억제 효능도 80% 에탄올 추출물 및 분획물들이 다소 차이는 있었지만 헥산과 디클로로메탄 분획물에서 IL-6와 IL-$1{\beta}$에서 생성억제 효과가 나타났다. 이러한 결과는 구실잣밤나무 잎에서 유효성분 추출을 통한 항염증 물질의 연구 또는 예방하거나 치료할 수 있는 염증 억제 성분의 분리 및 그 작용기전 연구에 중요한 기초 자료가 될 것이라 사료된다. 또한 구실잣밤나무 추출물로부터 염증억제 성분을 도출하고자 활성분획인 디클로로 메탄 분획물에 대하여 활성성분의 분리가 진행 중이다.

• 대한임상검사과학회지
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• 제52권3호
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• pp.253-260
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• 2020

알츠하이머 병은 인지 기능 저하로 인한 치매 발생으로 설명할 수 있는 만성 및 진행성 신경 퇴행성 질환이다. 알츠하이머 병의 특징은 세포 외 및 세포 내 아밀로이드 플라크의 형성이다. 아밀로이드 베타는 알츠하이머 병의 특징이며 미세아교세포는 아밀로이드 베타의 존재하에 활성화될 수 있다. 활성화된 미세아교세포는 전 염증성 사이토카인을 분비한다. 게다가, S100A9는 염증의 중요한 선천성 전 염증 기여자이며 알츠하이머 병에 잠재적인 기여자로 알려져 있다. 이 연구는 아밀로이드 베타 및 S100A9이 처리된 BV-2 세포에서 염증반응 및 NLRP3 인플라마솜 활성화에 대한 메트포르민 및 알파리포산의 효과를 조사했다. 메트포르민과 알파-리포산은 종양 괴사 인자-알파 및 일터루킨-6와 같은 염증성 사이토카인을 약화시킨다. 또한 메트포르민과 알파-리포산은 JNK, ERK, p38의 인산화를 억제하고, NF-kB 경로 및 NLRP3 인플라마솜의 활성화를 억제했다. 또한 메트포르민과 알파-리포산은 M1 표현형인 ICAM1의 수준을 감소시킨 반면 M2 표현형인 ARG1은 증가시켰다. 이러한 발견은 메트포르민과 알파-리포산이 아밀로이드베타 및 S100A9에 의한 신경 염증 반응에 대한 치료제가 될 수 있음을 시사한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3651-3657
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• 2014

Hepatocellular carcinoma (HCC) has a relatively higher incidence in many countries of Asia. Globally, HCC has a high fatality rate and short survival. Epirubicin, a doxorubicin analogue, may be administered alone or in combination with other agents to treat primary liver cancer and metastatic diseases. However, the toxic effects of epirubicin to normal tissues and cells have been one of the major obstacles to successful cancer chemotherapy. Here, we investigated the effects of epirubicin in combination with kappa-selenocarrageenan on mice with H22 implanted tumors and HepG-2 cell proliferation, immune organ index, morphology, cell cycle and related protein expressions in vivo and in vitro with sequential drug exposure. The inhibitory rate of tumor growth in vivo was calculated. Drug sensitivity was measured by MTT assay, and the King's principle was used to evaluate the interaction of drug combination. Morphological changes were observed by fluorescent microscopy. Cell cycle changes were analyzed by flow cytometry. Expression of cyclin A, Cdc25A and Cdk2 were detected by Western blotting. In vivo results demonstrated that the inhibitory rate of EPI combined with KSC was higher than that of KSC or EPI alone, and the Q value indicated an additive effect. In addition, KSC could significantly raise the thymus and spleen indices of mice with H22 implanted tumors. In the drug sensitivity assay in vitro, exposure to KSC and EPI simultaneously was more effective than exposure sequentially in HepG-2 cells, while exposure to KSC prior to EPI was more effective than exposure to EPI prior to KSC. Q values showed an additive effect in the simultaneous group and antagonistic effects in the sequential groups. Morphological analysis showed similar results to the drug sensitivity assay. Cell cycle analysis revealed that exposure to KSC or EPI alone arrested the cells in S phase in HepG-2 cells, exposure to KSC and EPI simultaneously caused accumulation in the S phase, an effect caused by either KSC or EPI. Expression of cyclin A, Cdc25A and Cdk2 protein was down-regulated following exposure to KSC and EPI alone or in combination, exposure to KSC and EPI simultaneously resulting in the lowest values. Taken together, our findings suggest that KSC in combination with EPI might have potential as a new therapeutic regimen against HCC.

• 한국식품영양과학회지
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• 제41권8호
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• pp.1057-1065
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• 2012

본 연구는 생약의 휘발성 향기추출액을 이용한 염증치료용 기능성 신소재를 개발하기 위해 대식세포주인 Raw 264.7 세포를 이용한 모델시스템에서 천궁 및 당귀의 휘발성 향기추출물의 항염증 효과를 검정하였으며, 아울러 이들 향기추출물의 향기성분을 GC-MS 분석을 통해 확인하였다. 그 결과 8가지 생약(노간주, 목향, 천궁, 당귀, 정향, 고본, 박하, 애엽)의 향기추출물 중 천궁 및 당귀가 LPS 처리에 의한 NO의 생성을 가장 크게 억제하였으며 $PGE_2$의 생성도 현저히 억제시키는 것으로 나타났다. 또한, 천궁 및 당귀의 향기 추출물은 NO의 생합성 효소인 iNOS 단백질의 발현 또한 농도의존적으로 감소시킴을 확인할 수 있었으며, 염증성 사이토카인인 IL-6의 생성 억제효과도 우수하였다. 천궁 및 당귀 향기추출물의 휘발성 향기성분을 GC-MS로 분석한 결과, 천궁은 eugenol, 3-butylphthalide, butylidene phthalide 및 ligustilide를 확인하였으며 이들 향기성분 중 ligustilide가 천궁의 주된 휘발성 향기성분임을 확인하였고, 당귀는 eugenol, ${\beta}$-maaliene, ${\beta}$-eudesmol 및 9-tetradecenoic acid를 확인하였으며 이들 향기성분 중 ${\beta}$-eudesmol이 당귀의 주된 향기성분임을 확인하였다. 이러한 연구결과로 미루어 볼 때 천궁 및 당귀의 휘발성 향기추출물이 대식세포에 의해 생성되는 염증반응의 매개물질인 NO, $PGE_2$, IL-6의 생성을 저해함으로써 항염증 활성을 가지는 것으로 생각되며, 이러한 항염증 활성은 천궁 및 당귀에 함유된 항염증성 향기성분인 ligustilide 및 ${\beta}$-eudesmol이 크게 기여했을 것으로 사료된다. 따라서 천궁 및 당귀의 휘발성 향기추출물은 천연 유래의 항염증 물질로서 잠재적인 가치가 있어 향후 염증질환 예방 및 치료용 기능성식품 및 화장품 소재로 활용할 수 있을 것으로 생각된다.

• Journal of Acupuncture Research
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• 제34권2호
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• pp.1-18
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• 2017

Objectives : The purpose of this study was to evaluate the effects of water extracts of Eucommiae cortex (EC), Psoraleae semen (PS), and their combination on receptor activator of nuclear factor-kappa-B ligand (RANKL)-induced osteoclast differentiation. Methods : We assayed the protein expression levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-Fos, mitogen-activated protein kinases (MAPKs), and ${\beta}-actin$ in cell lysates using western blotting. Similarly, mRNA expression levels of NFATc1, c-Fos, tartrateresistant acid phosphate (TRAP), and glyceraldehyde-3-phosphate dehydrogenase, spermatogeni (GAPDHS) from bone marrow macrophages (BMMs) were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, we determined the anti-osteoporotic effects of the water extracts of EC, PS, and their combination in a lipopolysaccharide (LPS)-induced bone-loss mouse model. Results : The in vitro data revealed showed that the combination of EC and PS extract showed a more remarkable inhibition of osteoclast differentiation than each herb did alone. The combination downregulated the induction of c-Fos, NFATc1, and TRAP by suppressing the phosphorylation of p38 and c-Jun N-terminal kinases (JNKs) and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). Lastly, the in vivo data showed that PS reduced the LPS-induced bone erosion. Conclusion : The result of this study suggests that EC and PS could be potential therapeutic agents for bone loss diseases such as osteoporosis.

• KSBB Journal
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• 제23권2호
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• pp.109-117
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• 2008

담자균류의 버섯은 대부분 영양생장단계의 균사체와 포자를 형성하는 생식생장단계인 자실체로 나누어진다. 그러나 자연산 상황버섯은 자연계에서의 분포수가 극히 적어 그 자실체를 얻기 어려우며, 이러한 희귀성으로 인해 매우 고가로 거래되고 있다. 1990년대 중반 상황버섯은 균사체 배양기술과 인공재배법이 확립된 후 농가에서 대량생산되기 시작하였으며, 이에 따라 상황버섯의 유효성분을 이용한 기능성 식품 및 의약품의 개발이 활발하였다. 그러나 인공재배법에 의한 상황버섯 추출물은 자연산 추출물의 항암 및 효능면에서 차이를 나타내고 있어, 자연산 자실체와 같은 수준에서의 약효를 나타내기 위한 인공배양기술과 고농도 유효성분을 획득하기 위한 추출법이 핵심기술로 대두되었고, 인공배양된 상황버섯과 자연산의 다각도적인 약효 비교에 관한 연구가 아직까지 진행되고 있다. 따라서 상황버섯의 유효성분이 높게 함유된 저렴한 추출물이 생산될 수 있는 기반 기술들이 기능성 음료용수, 식품 및 의약품으로 개발에 중요한 핵심기술로 떠오르고 있다. 국내 상황버섯 기능성 식품의 시장은 상황버섯의 효능에 대한 인지 증대, 웰빙열풍을 의한 건강 음료에 대한 선호도 증대 등으로 인해 향후에도 10% 이상의 높은 성장률을 보일 것으로 예상된다. 현재는 중소기업들이 주로 활동하고 있어 마케팅 및 유통의 한계로 인해 시장이 크게 확대되고 있지 않으나, 사업매력도가 긍정적으로 평가되고 있어 대기업에서도 상황버섯을 이용한 기능성 식품 시장에의 진출을 모색하고 있다.