• 한국식품저장유통학회지
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• 제24권2호
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• pp.303-311
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• 2017

본 연구에서는 숙성 흑율피 가루를 1, 3 또는 5% 첨가한 숙성 흑율피 양갱을 제조하여 품질 특성, 관능적 특성 및 항산화 특성을 분석하였다. 숙성 흑율피 양갱의 수분함량은 1% 첨가군은 대조군과 유사하였으나 숙성 흑율피 첨가량이 증가함에 따라 수분 함량은 증가하였다. 당도와 환원당은 숙성 흑율피 첨가량이 증가됨에 따라 낮아졌다. pH는 숙성 흑율피 첨가량이 증가함에 따라 감소하였고, 산도는 높아졌다. 명도(lightness)와 황색도(yellowness)는 숙성 흑율피 첨가량이 증가할수록 낮아졌으며, 적색도(redness)는 높아졌다. 기계적 조직감 측정결과, 경도(hardness)는 대조군이 높았고, 숙성 흑율피 첨가량이 증가함에 따라 경도는 증가하였다, 응집성(cohesiveness)은 숙성 흑율피 1% 첨가 양갱과 3% 첨가 양갱은 유의적인 차이를 나타내지 않았지만, 첨가량이 증가함에 따라 응집성은 감소하였다. 탄력성(springness)은 숙성 흑율피 첨가량이 증가할수록 낮아졌다. 총 페놀 함량은 숙성 흑율피 첨가량이 증가함에 따라 증가하였다. DPPH 라디칼 소거능과 hydroxyl 라디칼 소거능은 양갱에 숙성 흑율피 첨가량이 많을수록 $IC_{50}$ 값이 낮아져 항산화능이 높아졌다. 기호도 검사 결과, 숙성 흑율피 3% 첨가군의 전체적인 기호도 점수가 5.2점으로 가장 높은 점수를 받았다. 이상의 결과로부터 숙성 흑율피를 3% 첨가하여 양갱을 제조할 때 품질 특성, 항산화성 및 관능적 특성이 우수하였으므로, 이를 바탕으로 기능성 식품으로서 개발 가능성이 높을 것으로 사료된다.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.718-723
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• 2002

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (＞24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

• 대한약리학회지
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• 제29권1호
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• pp.131-137
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• 1993

Tetracycline계 약제가, 류마치양 관절염을 비롯한 염증성 질환들의 주된 병인으로 알려지고있는 호중구 elastase의 활성도를 억제하였으며, 특히 oxytetracycline, demeclocycline, 그리고 tetracycline 등은 분자 구조적 차이에 따라 elastase의 효소 활성도에 대하여 다양한 억제율을 나타내었다. 측쇄 구조의 5번 위치에 $OH{^-}$기가 첨가된 oxytetracycline이 가장 높은 억제율을 나타내었다. 억제 양상에 있어서도 tetracycline이 비경쟁적 저해 형태를 보인 반면에, oxytetracycline은 경쟁적 저해 형태를 나타내었으며, Ki값은 각각 4.9mM과 0.39mM로 산출 되었다. 또한 항균 효과를 나타내는 활성 부위를 제거시킨 de-dimethylaminotetracycline을 합성하여 효소 활성도 억제 실험에 사용한 결과, tetracycline과 유사한 효소 억제 작용을 나타냄을 확인하였다. 이상의 연구 결과에서, tetracycline의 효소 활성도 억제 작용은 항균 효과를 나타내는 활성 부위와 상관없이 독립된 기전에 의해서 일어나는 약리 작용이며, 측쇄 구조의 $OH{^-}$기가 이 작용에 영향을 주는 일부 원인인 것으로 추정할 수 있으며, 이를 tetracycline계 약제가 염증 부위에서 나타내는 분자 단계에서의 새로운 약리 기전으로 제시하고자 한다. 또한 de-dimethylaminotetracycline은 항균제의 장기 사용시에 발생할 수 있는 저항균의 출현과는 무관하므로, 다른 부작용에 대한 연구가 선행될 경우, elastase에 의해 야기되는 만성 질환들의 치료제로써 중요한 역할을 할 것으로 사료된다.

• Journal of Ginseng Research
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• 제42권4호
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• pp.562-570
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• 2018

Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.859-865
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• 2006

With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of $Na_5SeV_5O_{18}{\cdot}3H_2O$ (NaSeVO) in K562 cells. The results showed that $0.625{\sim}20\;mg/L$ NaSeVO could significantly inhibit the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29-5.22) mg/L after 48 hand 72 h treatment with NaSeVO respectively. In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5-5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of $Ca^{2+}$ and $Mg^{2+}$, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular $Ca^{2+}$, $Mg^{2+}$ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).

• Archives of Pharmacal Research
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• 제29권10호
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• pp.898-903
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• 2006

The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its anti platelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with $IC_{50}$ values of $620{\pm}12$, $823{\pm}22$, $722{\pm}21$ and $650{\pm}14\;{\mu}g/mL$, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.

• Journal of Ginseng Research
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• 제36권1호
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• pp.55-60
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• 2012

In a previous report, we demonstrated that ginsenoside Rc, one of major ginsenosides from Panax ginseng, enhances ${\gamma}$-aminobutyric acid (GABA) $receptor_A$ ($GABA_A$)-mediated ion channel currents. However, little is known about the effects of ginsenoside metabolites on $GABA_A$ receptor channel activity. The present study investigated the effects of ginsenoside metabolites on human recombinant $GABA_A$ receptor (${\alpha}_1{\beta}_1{\gamma}_{2s}$) channel activity expressed in Xenopus oocytes using a two-electrode voltage clamp technique. M4, a metabolite of protopanaxatriol ginsenosides, more potently inhibited the GABA-induced inward peak current ($I_{GABA}$) than protopanaxadiol (PPD), a metabolite of PPD ginsenosides. The effect of M4 and PPD on $I_{GABA}$ was both concentration-dependent and reversible. The half-inhibitory concentration ($IC_{50}$) values of M4 and PPD were 17.1${\pm}$2.2 and 23.1${\pm}$8.6 ${\mu}M$, respectively. The inhibition of $I_{GABA}$ by M4 and PPD was voltage-independent and non-competitive. This study implies that the regulation of $GABA_A$ receptor channel activity by ginsenoside metabolites differs from that of ginsenosides.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.492-501
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• 2019

Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

• 대한본초학회지
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• 제33권4호
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• pp.101-108
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• 2018

Objectives : This study aimed to effects antioxidant activity of citrus peel extract (CPE) and effect on its glucose metabolism in L6 rat skeletal muscle cells. Methods : Antioxidative activities were evaluated by using 10 kinds of natural materials, and total polyphenol and flavonoid contents were examined. The L6 muscle cells toxicity of CPE was examined by MTT assay. Expression of glucose-related genes in L6 muscle cells by CPE treatment was analyzed by real-time PCR and western blotting. Results : The $IC_{50}$ values of DPPH and ABTS free radical scavenging activity of CPE were ($15.47{\pm}0.26{\mu}g/m{\ell}$ and $12.07{\pm}1.23{\mu}g/m{\ell}$, respectively), effectively clearing DPPH and ABTS. CPE showed total polyphenol and flavonoid contents ($20.30{\pm}0.38$ and $64.20{\pm}0.52$, respectively). The selected CPE were used in experiments using an effective concentration that is not toxic in L6 muscle cells. We investigated insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase regulatory (PI3KR), Akt, and glucose transporter 4 (GLUT4). mRNA analysis by realtime PCR showed no significant difference, but CPE-treated cells showed a tendency to increase in concentration-dependent manner. However, analysis of protein expression of Akt and GLUT4 by western blotting showed that CPE treatment significantly increased concentration dependent (p<0.001). Conclusions : As a result, citrus peel extract with high antioxidant activity regulates glucose metabolism in L6 muscle cells. Therefore, CPE can be a potential treatment for the treatment of diabetes.

• 한국수산과학회지
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• 제56권1호
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• pp.7-20
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• 2023

Boil-dried concentrate (BDC) and steam-dried concentrate (SDC) were prepared from olive flounder Paralichthys olivaceus roe using the cook-dried process, and their food functionality and in vitro bioactivity were examined. The buffer capacity of BDC and SDC was found to be stronger in the alkaline region than in the acidic region, and the buffer capacity of SDC was superior to that of BDC. The water holding capacities of these concentrates were 7.6 and 7.4 g/g protein, respectively, both of which were significantly lower than that of freeze-dried concentrate (FDC). The solubility of BDC (13.4%) and SDC (12.7%), foaming capacity of BDC (107.7%) and SDC (110.6%), and oil-in-water emulsifying activity index of BDC (7.7 m²/g) and SDC (9.7 m²/g) were all significantly lower than the corresponding values for FDC (P<0.05). The lower food functionality of BDC and SDC compared with FDC can be attributed to the high-temperature denaturation of proteins during the cook-dried process. The 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activities (IC₅₀) of SDC (2.5 mg protein/mL) was 60.4 ㎍/mL, and the angiotensin I converting enzyme inhibitory activity was 80.9%. Olive flounder roe concentrates have good antioxidant and antihypertensive activities, and can be used as materials or ingredients in the processing of seafood and other foods to enhance protein contents and food functionality.