• Korean Journal of Pharmacognosy
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• v.27 no.3
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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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• v.22 no.3
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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.

• Korean Journal of Food Science and Technology
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• v.16 no.1
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• pp.23-28
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• 1984

Anchovy homogenates with or without salt were autolyzed at various pH and temperature conditions. In the initial hydrolysis during 20 hours, the highest autolysis of anchovy homogenate was achieved at pH 4 and $50^{\circ}C$. However, the addition of 20% salt changed the optimum condition to pH 6 and $50^{\circ}C$. When the digestion time was prolonged to 8 days, the most favorable temperature for the autolysis of salted anchovy was lowered to $40^{\circ}C$ compared with $50^{\circ}C$ of initial hydrolysis while the optimum pH was unchanged. Under the best conditions described above, 60.5% of anchovy nitrogen was converted to TCA-soluble nitrogen in 20 hr-incubation without salting, but it was reduced to 49.8% with salting. In the 8 days hydrolysis of salted anchovy, as much as 83.1% of total nitrogen was transformed into TCA-soluble nitrogen. Slight increase in the degree of hydrolysis up to 89.6% was occurred during subsequent ripening period of 52 days at ambient temperature.

• Herbal Formula Science
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• v.10 no.2
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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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• v.4 no.3
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.5
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• pp.707-712
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• 1995

Natural antimicrobial activities in leaf mustard Dolsan(Brassica juncea) were evaluated for food preservation. Antimicrobial activities and changes in volatile allylisothiocyanate(AIT) concentration were examined during incubation of leaf mustard homogenate for 72 hours at $30^{\circ}C$. The concentration of volatile AIT was highest at 2 hours of incubation. Antimicrobial activities, which were insignificant in raw homogenate without incubation, were occurred at 21 hours and were showed highest at 48~72 hours of incubation. Water-pretreated extract(WPE) showed the antimicrobial activity by 1.2~1.4 times higher than the water extract. Ethylacetate fraction of leaf mustard showed high antimicrobial activities. The WPE had strong antimicrobial activities against Salmonella typhimurium and Staphylococcus aureus. Heat treatment of the WPE for 30 min at $121^{\circ}C$ did not lose the antimicrobial activities.

• The Journal of Korean Medicine
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• v.37 no.4
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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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• v.26 no.1
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• pp.28-34
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• 1983

The change of lactate dehydrogenase(LDH) activity and the possibility of the existence of LDH. isozyme were examined with different parts of soybean sprout. The enzyme activity was little changed in cotyledons throughout the early stagy of germination. However, hypocotyls and roots showed the continuous decline of the enzyme activity since the radicle emerged from seeds. It was found that LDH from hypocotyls. and roots was unstable as compared with LDH from cotyledons, even at low temperature. The enzyme from hypocotyls and roots was not purified with a good yield when the purification procedure developed for LDH from cotyledons. was employed. LDH from hypocotyls and roots has the Rm value of 0.29, and 0.25 from cotyledons. The apparent Km value for LDH from cotyledons was 0.45mM with sodium pyruvate, while crude homogenate of hypocotyls or roots showed biphasic phenomenon with two Km values 0.014 and 0.45mM. The results indicate the possibility that crude homogenate of hypocotyls or roots may contain a different LDH isozyme from the LDH of soybean reported previously.

• Archives of Pharmacal Research
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• v.27 no.6
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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.

• YAKHAK HOEJI
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• v.40 no.3
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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).