• 약학회지
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• 제38권6호
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• pp.646-653
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• 1994

The pharmacokinetics of DWP305, a new combined preparation for hepatic disorders was examined in rats. DWP305 was composed of ursodeoxycholic acid(UDCA), Cardus marianus extract(silymarin 74.5%), fursulthiamine and riboflavin tetrabutyrate(RTB). Especially, this study was focused on the possibilities of drug interaction that the administration of DWP305 may affect the oral absorption of each component. After oral administration of DWP305 and each component drug to rats, the biliary excretion of silybin and tauroursodeoxycholic acid(TUDCA), and the urinary excretion of vitamins were measured by HPLC up to 48 hours. The cumulative amount of TUDCA or silybin in bile was not significantly different between DWP305 and UDCA/silymarin administered groups at doses of 25 and 100 mg/kg. In the case of vitamin study, the urinary thiamine excretion of equivalent molar fursulthiamine administered group was significantly higher than that of thiamine administered group. Urinary riboflavin level of equivalent molar RTB administered group was lower than that of riboflavin administered group, but not significant. These results suggest that the combined preparation may not affect the oral absorption of each component in respect of drug interaction. Also, fursulthiamine and RTB were more effective in oral absorption than thiamine and riboflavin, respectively.

• 동의생리병리학회지
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• 제20권5호
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• pp.1282-1284
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• 2006

In the course of search for hepatoprotective agents from oriental traditional medicines, one compound was isolated from the MeOH extract of the fruits of Schizandra chinensis, and its structure was determined as gomisin J(1). The evaluation for hepatoprotective activity of isolated compound 1 on drug-induced cytotoxicity was conducted, and compound 1 showed protective effect with an EC$_{50}$value of 86.0 ${\pm}$ 5.3 ${\mu}$M against tacrine-induced cytotoxicity in Hep G2 cells. One of the well-known hepatoprotective agents, silybin, used as a positive control, and the hepatoprotective effect of compound 1 is similar with that of silybin (EC$_{50}$ value = 90.5 ${\pm}$ 9.8 ${\mu}$M).

• 생약학회지
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• 제26권1호
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• pp.51-56
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• 1995

To devise an in vitro screening method for antihepatotoxic activity, $CCl_4-induced$ cytotoxicities in primary cultures rat hepatocytes were examined. When rat hepatocytes were intoxicated with 0.5, 1.0 or 1.5 mM $CCl_4$ for 1.5, 3 or 19hr, in order of LDH>GOT>GPT release form hepatocytes was increased in a dose-dependent manner. Treatment with 1.5 mM $CCl_4$ for 1.5 hr showed maximum increase in activity of LDH, GOT or GPT released in the medium compared with the control. At this experimental condition, well known antihepatotoxic substances, glycyrrhizin and silybin markedly inhibited $CCl_4-induced$ cytotoxicities. These results demonstrated that the screening method using $CCl_4-induced$ injury in primary cultured rat hepatocytes might be suitable in vitro assay for antihepatotoxic activity.

• Archives of Pharmacal Research
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• 제18권4호
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• pp.289-292
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• 1995

Icariside II, a flavonol glycoside, was isolated from the aerial part of Epimedium Koreanum Nakai by the anti-hepatotoxic acitivity guided fractionation technique employing $CCl_4-in-toxicated$ primary cultured rat hepatocytes as an assay system. Its anti-hepatotoxic activity was evaluated by measuring activity of glutamic pyruvic transaminase released from the $CCl_4-in-toxicated$ primary cultured rat hapatocytes. Icariside II significantly reduced the activity of glutamic pyruvic transaminase released from the $CCl_4-in-toxicated$ primary cultured rat hepatocytes and resulted in 78% recovery of the toxicity at the concentration of $200{\;}\mu\textrm{m}$. The anti-hepatotoxic activity of icariside II on the $CCl_4-in-toxicated$ primary cultured rat hepatocytes was as potent as that of silybin.

• Archives of Pharmacal Research
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• 제20권6호
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• pp.529-532
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• 1997

A $CHCl_3$:MeOH extract of the fruit of Lycium chinense Mill. (Solanaceae) was found to afford significant protection against carbon tetrachloride-induced toxicity in primary cultures of rat hepatocytes. Subsequent activity-guided fractionation resulted in the isolation of zeaxanthin and zeaxanthin dipalmitate as antihepatotoxic components. Incubation of injured hepatocytes with zeaxanthin dipalmitate reduced the levels of glutamic pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) released from damaged cells to 60.5% and 76.3% of those released from untreated controls, respectively. Zeaxanthin also reduced the levels of GPT and SDH to 68.5% and 61.3% of the levels of those released from the untreated contro. The results confirm the hepatoprotective activities of zeaxanthins. Antihepatotoxic activities of zeaxanthins are comparable to that of silybin.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.193.1-193.1
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• 2003

Activity-guided separation for the aerial parts of Rodgersia podophylla A. Gray gave a new acylated flavonoid, quercetin 3-O-${\alpha}$-L-(5$^2$-acetyl)-arabinofuranoside (1), together with six known flavonoids (2-7). Their hepatoprotective activities were determined by using the primary cultures of rat hepatocytes injured by H$_2$O$_2$. Quercetin 3-O-${\alpha}$-L-(3$^2$-acetyl)-arabinofuranoside (3), kaempferol 3-O-${\alpha}$-L-rhamnopyranoside (5) and quercetin 3-O-${\alpha}$-L-rhamnopyranoside (6) exhibited hepatoprotective activities comparable to silybin at the concentration of 50 mM (45.7, 50.8 and 57.3 %, respectively), and the new flavonoid 1 showed hepatoprotective activity at the concentration of 100mM (50.1%).

• Natural Product Sciences
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• 제11권3호
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• pp.119-122
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• 2005

In the course of searching for hepatoprotective agents from natural products, four compounds were isolated from the MeOH extract of Sanguisorbae Radix, as guided by their DPPH free radical scavenging activity. The structures were determined as 4,5-dimethoxy-3-hydroxybenzoic acid methyl ester (1), (+)-gallocatechin (2), methyl $6-O-galloyl-{\beta}-D-glucopyranoside$ (3), and pomolic acid $3-O-[{\alpha}-L-arabinopyranoside]-28-O-[{\beta}-D-glucopyranosyl]$ ester (ziyu-glycoside I) (4). Compounds 2 and 3 showed significant DPPH free radical scavenging effects, exhibiting $IC_{50}$ values of 11.4 and $13.0\;{\mu}M$, respectively. L-Ascorbic acid was used as a positive control and exhibited the $IC_{50}$ value of $50.3\;{\mu}M$. In evaluation of the hepatoprotective activity of the isolated compounds on drug-induced cytotoxicity, compound 2 showed the significant hepatoprotective effect with the $EC_{50}$ value of $91.84\;{\pm}\;11.0\;{\mu}M$ on tacrine-induced cytotoxicity in Hep G2 cells, while silybin, a positive control, exhibited $EC_{50}$ value of $122.4\;{\pm}\;12.5\;{\mu}M$.

• 생약학회지
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• 제38권2호통권149호
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• pp.176-180
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• 2007

Five liglans, sauchinone (1), di-0-methyltetrahydrofuriguaiacin B (2), manassantin A (3), manassantin B (4) and saucerneol B (5), have been isolated from the MeOH extract of Saururus chinesis roots. The evaluation for protective effect of compounds 1-5 against tacrine-induced cytotoxicity in human liver-derived Hep G2 cells was conducted. Compounds 1,2, and 5 showed significant protective effects with the EC$_{50}$ values of74.2${\pm}$0.9, 111.3${\pm}$0.8,64.3${\pm}$0.8 ${\mu}$M, respectively. Silybin, one of the well-known hepatoprotective agents, used as a positive control, and also showed protective effect with an EC$_{50}$ value of 86.2${\pm}$0.5 ${\mu}$M.

• Biomolecules & Therapeutics
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• 제8권3호
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• pp.269-275
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• 2000

Silibinin(silybin) is the active component of silymarin from Silybum marianum and has hepato-protective effect. It is water-insoluble and has low bioavailability. To improve its bioavailability, self-micro-emulsifying drug delivery system (SMEDDS) has been developed by Hanmi Pharmaceutical Company (Silyma $n^{R}$ 140 soft capsule). In this study, the pharmacokinetic profiles of Silyma $n^{R}$ were examined and compared it with a reference preparation, L Caps140 of B Pharmaceutical Company. This study was approved by Yonsei University Severance Hospital IRB(approval No. CR0004) and followed the bioequivalence test guideline of Korean FDA. Eighteen healthy adult volunteers were allocated based on 2$\times$2 Latin square cross-over design. They were given 2 capsules (each contains silymarin 140 mg (60 mg as silibinin)) of either drug at each period and crossed over after a week of drug-free washout period. Blood concentration of silibinin was measured by HPLC. The $C_{max}$ and AUC of the Silyma $n^{R}$ were 1542.0 $\pm$ 402.7 ng/ml and 3323.3 $\pm$ 824.7 ng.h/ml, respectively, and were significantly higher than those of reference preparation. The Tmax was 0.8 $\pm$ 0.3 h and significantly shorter than reference preparation. The $K_{e}$ and $T_{1}$2/ of both drugs were comparable. Percent differences in means against reference preparation were +88.3% for AUC, +222.6% for $C_{max}$, and -61.1% for $T_{max}$./.>././.>./.

• 생약학회지
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• 제36권3호통권142호
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• pp.224-228
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• 2005

Protective effects of various natural flavonoids on carbon tetrachloride $(CCl_4)-induced$ hepatotoxicity were investigated in primary cultured rat hepatocytes. Some of these flavonoids decreased the ALT and LDH releases induced by $CCl_4$ in A dose-dependent manner. Neohesperidin, hesperetin, baicalin, baicalein and quercetin inhibited $CCl_4-induced$ alanine aminotransferase (ALT) release. In addition, quercetin, quercitrin, neohesperidin, baicalin, baicalein and naringin reduced $CCl_4$ induced lactate dehydrogenase (LDH) leakage. Among these flavonoids, quercitrin, quercetin, baicalin and baicalein possessed potent protective effects and were selected for the further investigation on lipid peroxidation. These four flavonoids inhibited dose dependently $CCl_4-induced$ lipid peroxidation. Especially, the protective effects of quercetin and baicalein were similar to silybin as a well-known hepatoprotective agent. These results suggest that these four flavonoids have significant cytoprotective effects and possibility of therapeutic effect on chemical-induced liver diseases.