• 생약학회지
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• 제27권3호
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• pp.159-166
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• 1996

To evaluate hepatoprotective effects of G009, an hepatoprotective agent which was extracted from the mycelia of Ganoderma lucidum IY009, we were, studied using $CCl_4$-and galactosamine-induced hepatotoxicity in rats. The ratio of liver weight to body weight, the value of glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase (GPT) activities, the change of a lipids in serum, and the inhibitory activity of malondialdehyde (MDA) formation in serum and liver homogenate were determined in rats. G009 was not significantly changed of the ratio of liver weight to body weight and the content of lipids in serum, but reduced the serum GOT and GPT values in $CCl_4$-and galactosamine-induced hepatotoxicity in rat. Especially, protective effect of G009 on rat hepatic injuries induced by galactosamine was significantly appeared. $CCl_4$ increased markedly the formation of lipid peroxides in the liver homogenate, and serum. The increase of lipid peroxides by $CCl_4$-induced hepatotoxicity was markedly reduced by the treatment with G009. These results suggest that the hepatoprotective effects of G009 may be correlated with its anti-lipid peroxidative activity, therefore, it may be potential agent for hepatic disease.

• Journal of Pharmaceutical Investigation
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• 제22권3호
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• pp.185-196
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• 1992

To assess its suitability as a prodrug of 5-fluorouracil (5-FU), 1-glycyloxymethyl-5-FU HCl (GFU), a 5-fluorouracil derivative having a glycyloxymethyl group at the N-l position was synthetized. Its physicochemical properties and hydrolysis kinetics, in aqueous solution of pH $1{\sim}10$ and in the presence of human plasma or rat liver homogenate were studied. Its acute toxicity and antitumor activity against sarcoma 180 were also examined, GFU showed higher lipid/water partition coefficient than 5-FU. The calculated $pK_{\alpha}$ values of 5-FU and GFU were 8.02 and 7,20, respectively. The decomposition rates of GFU in aqueous solution showed a pH-dependence over the pH range used, which could be ascribed to solvent catalysed hydrolysis reaction at pH lower than 4,16 and to specific hydroxide ion hydrolysis reaction at pH higher than 4,16, The half-life of GFU was 6,9 min in 80% human plasma solution and less than 3 min in rat liver homogenate at $37^{\circ}C$, The $LD_{50}$ value of 5-FU was 240 mg/kg while that of GFU was 440.6 mg/kg (226 mg as 5-FU). Both of 5FU and GFU showed a strong antitumor activity, Therapeutic ratios of 5-FU and GFU were 3.07 and 3.55, respectively.

• 한국식품과학회지
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• 제16권1호
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• pp.23-28
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• 1984

멸치를 마쇄하여 자가소화시킬 경우 무염상태에서 20시간까지는 $50^{\circ}C$, pH 4라 최적조건이었고, 식염을 20% 첨가하였을 때는 $50^{\circ}C$, pH 6에서 가수분해가 가장 잘행해졌다. 한편 식염을 첨가하여 8 일동안 가수분해시킬 경우 최적조건이 $40^{\circ}C$, pH 6으로 변화하는 것으로 밝혀졌다. 상기한 최적조건에서 20시간동안 자가소화 시켰을 때 무염상태에서는 총질소중 60.5%가 TCA-가용성 질소를 가수분해되었으나 식염을 20% 첨가하였을 때는 49.8%로 낮아졌다. 그리고 가염상태에서 8 일간 가수분해 시킨 결과 총질소중 83.1%가 TCA-가용성질소로 분해되었고 계속하여 실온에서 52일간 숙성시킨 결과 총질소중 89.6%가 분해되었다.

• 대한한의학방제학회지
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• 제10권2호
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• pp.127-141
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• 2002

Objectives: Haeganjeon(HGJ) has been used for the treatment of liver disease in traditional medicine. The present study was carried out to evaluate the antioxidant and protective effects of HGJ extract on oxidative damage of hepatocytes by tert-butyl hydroperoxide(t-BHP). Methods: In the linoleic acid water-alcohol system, the levels of lipid peroxide(LPO) were determined by TBA method. The scavenging effect of HGJ on ${\alpha},{\alpha}-diphenyl-{\beta}-picrylhydrazyl$(DPPH) radical was determined according to the method of Hatano. In the Fenton system(ferrous ion reaction with hydrogen peroxide), the levels of hydroxyl radical induced LPO in rat liver homogenate were determined according to the method of TBA. Inhibitory effect of HGJ on superoxide generation was measured by xanthine-xanthine oxidase system. In order to evaluate antioxidative activity of HGJ in the liver cell, cultured normal rat liver cells(Ac2F) were prepared and incubated with or without HGJ. After 18hr, cells placed in DMEM medium without serum, and then incubated with 1mM tert-butyl hydroperoxide(t-BHP) for 2hrs. Viable cells were detected by MTT assay. Conclusions: In the linoleic acid autoxidation system, HGJ extract significantly inhibited the time course of the lipid peroxidation. These effects were similar to those of BHA HGJ extracts showed about 70% scavenging effect on DPPH radical. And HGJ extract inhibited the lipid peroxide formation in rat liver homogenate induced by hydroxyl radical derived from Fenton system. In addition, HGJ extract protected the cell death induced by t-BHP and significantly increased cell viability in the normal rat liver cell. These result indicated that HGJ extract might playa protective role against oxidative hepatic cell injury by means of free radical scavenger.

• Biomolecules & Therapeutics
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• 제4권3호
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• pp.244-250
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• 1996

In this study, the anti-lipidperoxidative effects of G009, a polysaccharide extracted from Ganoderma lucidum IY009, was determined in ascorbic acid-$Fe^{2+}$-adenosine 5-diphosphate-intoxicated rat. In a model of ascorbic acid-Fe$^{2+}$-adenosine 5-diphosphate-induced hepatotoxicity in rat, G009 exhibited anti-lipidperoxidative effect in rat liver homogenate, and that malondialdehyde values of the liver homogenate inhibited from 48.1% to 74.8% in comparison to controls (p<0.05). The malondialdehyde formation in serum inhibited 66.5% at 100 mg/kg of G009. Also, serum levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in peroxidizer-induced rats treated with G009 was decreased compared with control. Especially, the formation of lipid peroxides in serum was related to glutamic pyruvic transaminase levels. These results suggest that G009 has a protective effect on ascorbic acid-$Fe^{2+}$-adenosine 5-diphosphate-induced hepatic injury through an inhibition of lipid peroxidation in liver.r.

• 한국식품영양과학회지
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• 제24권5호
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• pp.707-712
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• 1995

돌산갓 중의 천연 항균활성 물질을 이용하여 식품의 보존 효과를 증진시킬 목적으로, 갓을 물로 전처리하여 항균활성과 allylisothiocyanate(AIT) 함량을 조사하였다. 갓을 마쇄하여 $30^{\circ}C$에서 72시간 까지 진탕하면서 전처리할 때, 휘발성 AIT 함량은 전처리 2시간에서 가장 많았고, 전처리한 농축물 추출물(WPE)의 항균활성은 21시간 이후 부터 나타나서 48~72시간에 가장 강하게 나타내었고, 농축하지 않은 것은 WPE와는 달리 2~3시간에서도 항균활성을 나타내었지만 20시간 이후 부터는 동일한 패턴의 항균활성을 나타내었다. Ethylacetate 분획물에서 항균활성이 높았으며, 갓의 WPE는 전처리하지 않은 것보다 1.2~1.4배 항균활성이 증가되었다. WPE는 S. typhimurium과 S. aureus에 강한 저해활성을 나타내었으며, $121^{\circ}C$, 30분간 열처리하여도 항균활성은 거의 그대로 유지되었고, 전처리하지 않은 것은 항균활성이 거의 없거나 약하게 나타났다.

• 대한한의학회지
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• 제37권4호
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• pp.1-9
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• 2016

Objectives: The aim of this study was to solve skin moisturizing action mechanism issues of pomegranate concentrated solution (PCS) and dried pomegranate concentrate powder (PCP), at least partially. Materials and methods: In this study, ceramide and $TGF-{\beta}1$ contents with $TGF-{\beta}1$ mRNA expressions were analysis on the skin tissue homogenate samples after 56 days of continuous oral administration of PCS 1, 2, and 4 ml/kg, and PCP 100, 200 and 400 mg/kg. Results: Noticeable and dose-dependent increases of skin $TGF-{\beta}1$ contents and mRNA expressions were demonstrated in all PCP and PCS treated mice as compared with intact vehicle control, but no significant changes on the skin ceramide contents were demonstrated in all PCP and PCS treated mice as compared with intact vehicle control, in the current study. In addition, PCP 200 mg/kg showed similar increases of the skin $TGF-{\beta}1$ contents and mRNA expressions as compared to those of PCS 4 ml/kg. Conclusions: The presented results suggested that in vivo skin moisturizing effects of PCP and PCS after oral administration through up regulation of hyaluronan synthesis demonstrated in our previous results, may be possibly mediated by modulation of $TGF-{\beta}1$ expressions at least partially, without critical influences on the skin ceramide contents.

• Applied Biological Chemistry
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• 제26권1호
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• pp.28-34
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• 1983

발아초기(發芽初期)에 콩(대두(大豆))의 부위별(部位別)로 Lactate dehydrogenase(LDH)의 Isozyme 존재가능성(存在可能性)을 조사(調査)하기 위한 기초적(基礎的)인 연구(硏究)가 수행(遂行)되었다. 발아가 진행(進行)됨에 따라 자엽부위의 효소활성변화(酵素活性變化)에는 큰 유의성이 나타나지 않았으나, 배축이나 뿌리 부위(部位)에서는 감소하는 경향을 보였으며 $4{\sim}7^{\circ}C$에서 배축이나 뿌리로부터 얻은 LDH는 자엽에서 얻은 LDH에 비(比)해 불안정(不安定)했다. 전기영동상의 Rm value가 자엽으로부터 얻은 효소(酵素)에서는 0.25인데 비하여, 배축으로 부터 분리된 LDH는 0.29였다. 배축이나 뿌리로 부터 분리된 LDH는 Biphasic으로 0.45mM과 0.014mM의 두 km값을 보이고 자엽부위에서는 0.45mM 값만 관찰할 수 있었다. 이상의 결과는 자엽부위의 LDH와는 다른 성질(性質)을 가진 LDH가 배축이나 뿌리부위(部位)에 존재(存在)할 가능성(可能性)을 보여주고 있다.

• Archives of Pharmacal Research
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• 제27권6호
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• pp.662-669
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• 2004

The highly water-soluble monomethoxypoly(ethyleneglycol) (mPEG) prod rugs of cyciosporin A(CsA) were synthesized. These prod rugs were prepared by initially preparing intermediate in the form of carbonate at the 3'-positions of CsA with chloromethyl chloroformate, in the pres-ence of a base to provide a 3'-carbonated CsA intermediate. Reaction of the CsA intermediate with mPEG derivative in the presence of a base provides the desired water-soluble prod rugs. As a model, we chose molecular weight 5 kDa mPEG in the reaction with CsA to give water soluble prodrugs. To prove that the prod rug is decomposed in the body to produce CsA, the enzymatic hydrolysis test was conducted using human liver homogenate at $37^{\circ}C$. The prodrug was decomposed in human liver homogenate to produce the active material, CsA, and the hydrolysis half-life ($t_{1/2}$) of the prodrug, KI-306 was 2.2 minutes at $37^{\circ}C$. However, a demon-stration of non-enzymatic conversion in pH 7.4 phosphate buffer was provided by the fact that the half-life ($t_{1/2}$) is 21 hours at 37$^{\circ}C$. The hydrolysis test in rat whole blood was also conducted. The hydrolysis was seen with half-life ($t_{1/2}$) of about 9.9, 65.0, 14.2, 3.4, 2.1 9.5, and 1.6 minutes for KI-306, 309, 312, 313, 315, 316, and 317, respectively. This is the ideal for CsA prodrug. The pharmacokinetic study of the prodrug, KI-306, in comparison to the commer-cial product (Sandimmune Neoral Solution) was also carried out after single oral dose. Each rat received 7 mg／kg of CsA equivalent dose. Especially, the prodrug KI-306 exhibits higher AUC and $C_{max}$ than the conventional Neoral. The AUC and $C_{max}$ were increased nearly 1.5 fold. The kinetic value was also seen with $T_{max}$ of about 1.43 and 2.44 hours for KI-306 and Neoral, respectively.

• 약학회지
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• 제40권3호
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• pp.279-292
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• 1996

To assess their stability as a prodrug of 5-fluorouracil (5-FU), four N-acyloxycarbonyl derivatives (1-(N-tert-butyloxycarbonyl)glycyloxymethyl-5-FU :BGFU, 1-(N-tert-butyloxycar bonyl)-leucyloxymethyl-5-FU:BLFU, 1-(N-tert-carbobenzyloxymethyl) glycyloxymethyl-5-FU:CGFU and 1-(N-tert-carbobenzlyoxymethyl)leucyloxymethyl-5-FU:CLFU) possessing differently protected amino acids, and two acetic acid derivatives (5FU-1-acetylpentane:FUAP and 5-FU-1-acetylhexane:FUAH) were synthesized and their physicochemical properties, hydrolysis kinetics, acute toxicity and antitumor activity were evaluated. The lipid-water partition coefficients of six 5-FU prodrugs were higher than that of 5-FU and their aqueous solubilities were in the following rank order; BGFU>FUAP>CGFU>BLFU>CLFU${\simeq}$FUAH. The hydrolysis of N-acyloxycarboyl derivatives, greater at higher pH, was enhanced in presence of liver homogenate or human plasma. Meanwhile, acetic acid ester derivatives, very stable, were hydrolyzed by liver homogenate. Absorption rate constants were 0.181, 0.121, 0.111, 0.168, 0.168, 0.116 and 0.125 $hr^{-1}$ for 5-FU, BGFU, BLFU, CGFU, CLFU, FUAP and FUAH, respectively. The cytotoxicity of N-acyloxycarbonyl derivatives was 4 to 5 times lower than that of 5-FU, but that of acetic acid ester derivatives was negligeble. The $LD_{50}$ values were 204, 325.97 (133.59, amount as 5-FU), 708.16 (262.13), 663.50 (211.77), 382.33 (192.54) and 272.33 (130.09) mg/kg for 5-FU, BGFU, CGFU, CLFU, FUAP and FUAH, respectively. While N-acyloxycarbonyl derivatives showed enhanced antitumor activity and therapeutic ratio (3.30, 3.06, 4.19, 3.11 and 1.81 for BGFU, BLFU, CGFU, CLFU and 5-FU, respectively), FUAH and FUAP showed a smaller therapeutic ratio (0.79 and 0.83).