• Archives of Pharmacal Research
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• 제18권6호
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• pp.449-453
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• 1995

The search for patinum (II)-based compounds with improved therapeutic properties was prompted to design and synthesize a new family of water-soluble, third generation cis-diamminedichlorplatinum (II) complexes linked to uracil and uridine. Six heretofore undescribed uracil and uridine-platinum (II) complexes are ; [N-(2-aminoethyl)uracil-5-carboxamide]dichloroplatinum (II)(3a), [N-2(2-aminoethyl)uracil-6-carboxmide]dichloroplatinum (II) (3b),[5-(2-aminorthyl)carbamoyl-2',3',5',-tri-O-acetyluridine] dichloroplatinum (II) (6b), [5-(2-aminoethyl)-carbamoyl]-2',3',5',-tri-O-acetyluridine] dichloroplatinum (II) (6b), [5-(2-aminoethyl)carbamoylu-ridine]dihloroplatinum (II) (7a), [6-(2-aminoethyl)carbamoyluridine]dichloroplatinum (II) (7b). These analogues were prepared from the key starting materials, 5-carboxyuracil (1a) and 6-carboxyuracil (1b) which were reacted with ethylenediamine to afford the respective N-(2-aminoethyl)uracil-5-carboxmide (2a) land N-(2-aminoethyl)uracil-6-carboxamide (2b). The cisplatin complexes 3a and 3b were obtained through the reaction of the respective 2a and 2b ficiently introduced on the .betha.-D-ribose ring via a Vorbruggen-type nucleoside coupling procedure with hexamethyldisilazane, trimethylchlorosilane and stannicchloride under anhydrous acetonitfile to yield the sterospecific .betha.-anomeric 5-carboxy-2',3',5'-tri-O-acetyluridine (4a) and 6-carboxy-2',3',5'-tri-O-acetyluridine (4b), respective 5-(2-aminoethyl)carbamoyl-2',3',5'-tri-O-acetyluridine (5a) and 6-(2-aminoethyl)carbamoyl-2',3',5'-tri-O-acetyluridine (5b). The diamino-uridines 5a and 5b were reacted with potassium tetrachloroplatinate (II) to give the novel nucleoside complexes, 6a and 6b respectively which were deacetylated into the free nucleosides, 7a and 7b by the treatment with CH/sub 3/ONa. The antitumor activities were evaluated against three cell lines (K-562, FM-3A and P-388).

• Archives of Pharmacal Research
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• 제29권8호
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• pp.633-644
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• 2006

In last couple of decades the use of natural compounds like flavonoids as chemopreventive agents has gained much attention. Our current study focuses on identifying chemopreventive flavonoids and their mechanism of action on human prostate cancer cells. Human prostate cancer cells (PC3), stably transfected with activator protein 1 (AP-1) luciferase reporter gene were treated with four main classes of flavonoids namely flavonols, flavones, flavonones, and isoflavones. The maximum AP-1 luciferase induction of about 3 fold over control was observed with $20\;{\mu}M$ concentrations of quercetin, chrysin and genistein and $50\;{\mu}M$ concentration of kaempferol. At higher concentrations, most of the flavonoids demonstrated inhibition of AP-1 activity. The MTS assay for cell viability at 24 h showed that even at a very high concentration $(500\;{\mu}M)$, cell death was minimal for most of the flavonoids. To determine the role of MAPK pathway in the induction of AP-1 by flavonoids, Western blot of phospho MAPK proteins was performed. Four out of the eight flavonoids namely kaempferol, apigenin, genistein and naringenin were used for the Western Blot analysis. Induction of phospho-JNK and phospho-ERK activity was observed after two hour incubation of PC3-AP1 cells with flavonoids. However no induction of phospho-p38 activity was observed. Furthermore, pretreating the cells with specific inhibitors of JNK reduced the AP-1 luciferase activity that was induced by genistein while pretreatment with MEK inhibitor reduced the AP-1 luciferase activity induced by kaempferol. The pharmacological inhibitors did not affect the AP-1 luciferase activity induced by apigenin and naringenin. These results suggest the possible involvement of JNK pathway in genistein induced AP-1 activity while the ERK pathway seems to play an important role in kaempferol induced AP-1 activity.

• Journal of Ginseng Research
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• 제44권1호
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• pp.105-114
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• 2020

Background: Exploring the pharmacokinetic (PK) changes of various active components of single herbs and their combinations is necessary to elucidate the compatibility mechanism. However, the lack of chemical standards and low concentrations of multiple active ingredients in the biological matrix restrict PK studies. Methods: A putative multiple reaction monitoring strategy based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to extend the PK scopes of quantification without resorting to the use of chemical standards. First, the compounds studied, including components with available reference standard (ARS) and components lacking reference standard (LRS), were preclassified to several groups according to their chemical structures. Herb decoctions were then subjected to ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis with appropriate collision energy (CE) in MS² mode. Finally, multiple reaction monitoring transitions transformed from MS² of ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were used for ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry to obtain the mass responses of LRS components. LRS components quantification was further performed by developing an assistive group-dependent semiquantitative method. Results: The developed method was exemplified by the comparative PK process of single herbs Radix Ginseng (RG), Radix Polygala (RP), and their combinations (RG-RP). Significant changes in PK parameters were observed before and after combination. Conclusion: Results indicated that Traditional Chinese Medicine combinations can produce synergistic effects and diminish possible toxic effects, thereby reflecting the advantages of compatibility. The proposed strategy can solve the quantitative problem of LRS and extend the scopes of PK studies.

• 약학회지
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• 제54권5호
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• pp.341-347
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• 2010

The majority of forensic autopsies in Korea are performed by the National Institute of Scientific Investigation (NISI), and the NISI has carried out about 4,000 cases annually. Total 4,578 autopsies were performed by NISI in 2009, among them 2,918 cases (64%) were carried out at main office of NISI in Seoul, which is in charge of Seoul, Incheon and Gyeonggi province. In this study we investigated pattern of drugs & poisons in autopsy cases for recent three years in Korea. Postmortem specimens (bloods, gastric contents, etc) from autopsy cases by main office of NISI during 2007~2009 were screened for drugs & poisons. Using laboratory information management system of NISI (iLIMS), the kinds of drugs & poisons and the frequency were investigated. As the results, 1,705 cases were negative to drugs & poisons, it occupied 58% of total 2,918 autopsy cases in 2009. During three years (2007~2009), the kinds of drugs & poisons detected in specimens were 206, 185 and 203, respectively, and top three drugs were atropine (anticholinergic), chlorpheniramine (antihistamine) and lidocaine (local anaesthetic/anti-arrythmic). These drugs were supposed to be used not so much for suicidal or homicidal purpose as for therapeutic purpose in hospital. Meanwhile cyanide showed the highest frequency of poisons during 2007~2009, and the frequency was 32 cases in 2009. In case of pesticides, poisoning by paraquat (herbicide, 17 cases) showed the highest frequency, and methomyl (insecticide, 9 cases) and glyphosate (herbicide, 7 cases) were followed. Finally we selected 62 drugs as target drugs for systematic toxicological analysis (STA) for Korea. Poisons such as pesticides, natural toxins, volatile compounds should be included for STA in further study.

• 생명과학회지
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• 제26권6호
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• pp.651-656
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• 2016

벌 화분은 꿀벌로부터 생산되며 자연으로부터 얻을 수 있는 가장 균형 잡힌 영양 식품으로 받아들여지고 있다. 역사적으로도 벌 화분은 질병치료와 에너지 보충의 목적으로 사용되어 왔다. 최근의 연구 결과에서는 벌 화분의 항산화, 항염증, 심지어 항암작용과 같은 다양한 생리활성이 과학적으로 규명되고 있다. 그러나 벌 화분은 exine이라는 외피로 둘러싸여 있어 강산이나 고압 그리고 소화효소 등에 매우 저항성이 강한 것으로 밝혀졌고, 이로 인하여 생체이용률이 낮아 영양공급과 임상적 이용에 제한을 받고 있다. 본 연구는 벌 화분의 외피를 분쇄할 수 있는 습식분쇄기술을 개발하여 벌 화분의 생리활성을 분석하고자 기획되었다. 먼저 습식분쇄를 통해 벌 화분의 외피가 효과적으로 분쇄됨을 현미경을 통해 확인하였다. 게다가 습식분쇄에 의해 벌 화분의 활성성분으로 잘 알려진 polyphenol 화합물의 양이 약 11배 증가하였고 ABTS 항산화 분석법과 DPPH 라디칼 소거능 시험을 통해 항산화 효과가 증가함을 확인하였다. 이러한 결과는 습식분쇄기술을 통해 벌 화분을 임상적 및 향장 목적으로 사용할 수 있음을 증명한다.

• KSBB Journal
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• 제21권2호
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• pp.157-163
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• 2006

본 연구에서는 초임계 ASES 공정을 이용하여 인체내 및 피부에 여러 가지로 유익한 대표적 생리활성물질인 Vitamin-C의 불안정성을 극복하기 위하여 HP-${\beta}$-CD와의 포접복합체를 제조하여 수용액상에서의 안정성을 분석하였다. X-선 회절을 이용한 Vitamin-C와 HP-${\beta}$-CD의 결정성 분석으로 초임계 ASES 공정을 통하여 포접복합체가 용이하게 형성될 수 있음을 확인하였다. HP-${\beta}$-CD가 Vitamin-C의 안정성을 향상시키는 방법으로 이용될 수 있음을 확인하였으며, $25{\pm}0.1^{\circ}C$의 온도를 유지한 pH 7.0의 50 mM 인산완충용액 상에서 순수한 Vitamin-C, 물리적인 혼합물 및 용매증발법과 초임계 ASES 공정을 이용하여 제조된 포접복합체의 Vitamin-C 겉보기 1차 분해 속도 상수는 각각 $1.45{\times}10^{-2}h^{-1},\;1.41{\times}10^{-2}h^{-1},\;1.34{\times}10^{-2}h^{-1},\;0.20{\times}10^{-2}h^{-1}$로 초임계 ASES 공정으로 제조된 포접복합체의 경우 Vitamin-C의 안정성이 매우 크게 향상되는 것을 확인하였다.

• 한국발생생물학회지:발생과생식
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• 제10권3호
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• pp.169-175
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• 2006

전세계적으로 널리 복용되고 있음에도 불구하고 인삼이 중추신경계에 미치는 효과에 대한 세포수준에서의 증거는 별로 없다. 따라서 본 연구자들은 지금까지 보고된 30여종 이상의 ginsenosides 중에서 인삼 효과의 주된 활성성분으로 알려져 있는 Rb1과 Rg1을 이용해 해마신경전구세포의 분화와 증식에 미치는 효과를 연구하였다. 증식실험결과 Rb1과 Rg1을 3일 동안 해마신경전구세포에 처리하면 대조군에 비해 BrdU(+)세포수가 상당히 감소한 반면에 분화조건에서 Rb1과 Rg1을 처리했을 때는 신경세포특이적인 MAP2 단백질을 발현하는 세포수가 증가하였다. 전구세포의 신경세포로의 분화 결정에 관여한다고 잘 알려져 있는 proneural 전사인자인 Ngn1과 Hes1 유전자의 발현양상도 대조군에 비해 증가하였다. 따라서 본 연구 결과, ginsenoside Rb1과 Rg1은 해마신경전구세포의 증식을 감소시키고 대신 신경세포로의 분화를 촉진시킴으로써 해마신경발생에 관여함을 보여준다.

• 대한화장품학회지
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• 제41권4호
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• pp.375-382
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• 2015

진세노사이드(인삼 사포닌)는 인삼의 대표적 약리성분 중의 하나로 생물학적 활성을 가진 배당체 화합물이다. 이들 사포닌은 가수분해 되어 저분자화 되었을 때, 항주름 및 항산화, 항암 등에 높은 약리효능효과를 나타낸다. 본 연구에서는 인삼 esculin 배지를 활용하여 ${\beta}$-glucosidase 활성을 가진 균주를 분리하였고 인삼 사포닌 전환을 미생물을 이용하여 수행하였다. 본 균주들을 16S rRNA sequencing을 통하여 동정하여 본 결과 Stenotrophomonas rhizopilae strain GFC09로 확인되였다. 균주의 최적 활성 조건을 결정하기 위해 조효소 1 mM와 인삼사포닌 $Rb_1$과 함께 배양한 후 생물학적 전환을 TLC, HPLC를 사용하여 확인하였다. 조효소에 의한 인삼 사포닌 $Rb_1$의 전환 경로는 다음과 같다. LB: RbNeobio R&D center, Gyeonggi-do 16954, Korea${\rightarrow}$Rd${\rightarrow}$FNeobio R&D center, Gyeonggi-do 16954, Korea${\rightarrow}$compound K, TSB: $Rb_1{\rightarrow}Rd{\rightarrow}F_2$. 가수분해된 생성된 물질은 NMR로 구조 동정하였다. 전환 산물의 효능 분석결과, 콜라겐 생성을 농도 의존적으로 증가시키는 것이 관찰되었다. 이에 본 연구에서는 ginsenoside $F_2$와 compound K 함유 인삼 전환 산물의 주름 개선 소재로서 활용가능성을 확인하였다.

• 한국자원식물학회지
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• 제23권2호
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• pp.131-137
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• 2010

본 연구에서는 타타리메밀싹을 이용한 고부가가치 가공상품을 개발하기 위하여 타타리메밀싹 발효추출물의 영양성분과 생리활성을 검정하였다. 일반 영양성분분석에서는 메밀싹 발효추출물은 단백질, 나트륨, 아연, 마그네슘에서 약간 높은 함량을 보였으나, 메밀전초 발효추출물은 나머지 무기물과 비타민에서 높게 나타났다. 동물실험을 통한 항당뇨 및 혈중지질에 관한 생리활성 검정 결과, 메밀싹 발효추출물이 짧은 기간의 실험임에도 불구하고 혈중 LDL-cholesterol의 수치를 낮추고, HDL-cholesterol의 수치를 올려주어 혈중 total lipid를 낮추는 것을 알 수 있었다. 또한 동맥경화지수인 atherogenic index의 감소를 나타내었다. 이상의 결과를 종합해 볼 때 타타리메밀싹의 발효추출물은 혈중 지질의 개선을 통해 순환기 질환에 효과를 줄 수있다는 가능성을 제시하였다. 하지만 제품화하여 메밀의 새로운 수요창출 및 부가가치를 높이기 위해서는 장기적인 동물실험 및 제품이 갖추어야 할 조건에 대한 관능검사 등 추가적인 연구를 필요로 한다.

• 한국토양비료학회지
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• 제48권5호
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• pp.421-427
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• 2015

Angelica gigas Nakai is one of the most widely used herbal medicines and is known to have many pharmaceutical effects including an anti-oxidant, anti-cancer etc. This study was carried out to investigate an effect of fertilization on leaf yield, production of dry-matter and accumulation of pyranocurmarine compounds such as decursin (DE) and decursinol angelate (DA) in Angelica gigas Nakai. Effect of fertilization was determined from response surface regression equation composing of 2 by 3 factorial arrangement of urea, sodium dihydrogen phosphate and potassium chloride. Yield of leaf in Angelica gigas Nakai significantly increased until 100 days after transplanting. Production of leaf also tended to increase with increasing nitrogen fertilization. Model of regression equation showed that leaf production depended upon nitrogen ($Pr>{\mid}t{\mid}$ : 0.087, 0.256 and 0.079). Also, statistical results between nitrogen application level and production of dry-matter showed significant relationship (p<0.05) and contents of dry-matter was highest in 10 kg 10a-1 treatment on 24 Sep. Active compound isolated and purified from leaf and root of Angelica gigas Nakai was identified as DE and DA by gas chromatograph-mass spectrophotometry (GC-MS). Concentration of DA as prevalent compound in leaf was highest on 20 Aug. but decreased on 24 Sep. Amount of DE and DA accumulated in Angelica gigas Nakai significantly increased with growth stages and nitrogen level. The result of our investigation imply that nitrogen fertilization is important factor for production of leaf and accumulation of pyranocurmarine in Angelica gigas Nakai as a medicinal/food materials.