• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.213-222
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• 1994

The acute tonicity of DWP305 (Ursodeoxycholic acid : Silymarin : Fursulthiamine : Riboflavin tetrabutyrate=1: 1 : 0.1 : 0.05) was evaluated in both sexes of Sprague-Dawley rats, 6weeks old by the oral route of administration. DWP305 was not considered to induce any toxic effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that LD$_{50}$ value in rats would be above 5 g/kg in the oral administration. Subacute toxicity of DWP305 was examined in Sprague-Dawley rats. Four groups of rats were administered orally at doses of 0, 0.32, 0.8, and 2.0 g/kg/day of DWP305 for one month. Any significant toxic clinical symptom was not observed in the treated rats during the experimental period. Macroscopic examination on the organs of tested animals showed no abnormal findings. On autopsy, no significant changes were found in organs examined. Maximum tolerated dose of DWP305 for the rat was estimated to be above 2 g/kg in this study.y.

• Journal of Applied Biological Chemistry
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• v.51 no.6
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• pp.302-306
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• 2008

To evaluated active principles for diabetic compolications from the Taraxacum mongolicum (T. mongolicum), Cirsium japonicum (C japonicum), and Cirsium setidens (C. setidens) and its constituents, as well as silymarin tested for their effect on rat lens aldose reductase. As a result, the MeOH extract of T. mongolicum ($IC_{50}\;8.71\;{\mu}g/mL$) have strong lens aldose reductase inhibition abilities. Also, Aldose reductase inhibitory showed an isolated luteolin ($IC_{50}\;20\;{\mu}M$) from the T. mongolicum and sliymarin ($IC_{50}\;13\;{\mu}M$).

• The Journal of Korean Medicine
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• v.29 no.3
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• pp.124-130
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• 2008

Herbal plants or traditional Oriental medicine have been considered as a potential resource of new drug development worldwide. However, traditional Korean medicine has given little effort to the field of new drug development. This study reports on a plant-derived hepatotherapeutic drug, silymarin, which has been popularly used in many countries. It was discovered as an active compound from Silybum marianum (milk thistle) which has been known as a medicinal plant having hepatoprotective properties in both European and Asian countries. While it has been used as an herbal prescription in Asia, its active compounds or scientific mechanisms were intensively studied in Europe. Currently, silymarin is one of the most powerful herbal extracts in the world, and its usage is being expanded to many other medical purposes. This report would be helpful for providing an informative example of herbal-derived drug development to Oriental doctors or scientists in the Oriental medicinal field.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.112-112
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• 1995

간장 손상시에는 여러 혈청의 효소 활성과 함께 혈청 $\beta$-glucuronidase의 활성도 증가한다는 것이 보고되었으나 심한 간부전이나 간암의 경우 이들의 활성은 오히려 정상치보다 감소하는 것으로 나타났다. Silymarin은 간장 보호효과로 이미 임상에 널리 사용되고 있는 약물로서 김 등에 의해 silymarin이 장내세균의 $\beta$-glucuronidase와 간장의 $\beta$-glucuronidase의 활성을 억제한다는 것이 보고되었다. 이에 연자 둥은 $\beta$-glucuronidase의 저해 효과가 관찰된 영지버섯온 유기용매로 분획하여 간장 보호효과를 검색하였다. 영지버섯의 70% MeOH 추출물(GT)과 그 ether 분획(GE)에 대해 생쥐 1군을 6마리로 하여 20% $CCl_4$0.1$m\ell$/10g(olive oil로 희석)을 경구투여 하였다. 검액 GE는 50mg/kg과 250mg/kg, GT는 100mg/kg과 500mg/kg을 각각 사염화탄소 투여 30분 전에 경구투여 하였으며 사염화탄소를 투여하고 24시간 후에 심장 채혈하고 혈청을 분리하여 혈청성분 및 혈청효소의 활성을 측정하였다. 대조군에는 생리식염수를 투여하였고 양성 비교약물로는 silymarln 100mg/kg을 경구투여 하여 비교 관찰하였다. 실험 결과, 영지버섯의 ether 분획에서는 혈청중 GOT, GPT의 활성과 triglyceride의 함량에 대해 silymarin보다 우수한 효과를 보였으며, 70% MeOH 추출물은 silymarin에 미치지 못했다.

• Biomolecules & Therapeutics
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• v.8 no.3
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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 $T_{max}$./.>././.>./.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.11
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• pp.1562-1568
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• 2013

This study was conducted to evaluate the effects of indigenous herbal supplements on growth, blood metabolites and carcass characteristics in the late fattening period of Hanwoo steers. In a 6 month feeding trial, thirty Hanwoo steers ($647{\pm}32$ kg) were allotted to one of 5 treatment groups, control (basal diet contained lasalocid), licorice, clove, turmeric and silymarin, with six steers per pen. All groups received ad libitum concentrate and 1 kg rice straw/animal/d throughout the feeding trial. Blood samples were collected at the beginning, middle, and the end of the experiment and the steers were slaughtered at the end. Blood glucose, triglyceride, total protein, and albumin concentrations were higher in the turmeric treatment compared with other treatments. Blood urea nitrogen and creatinine concentrations were highest (p<0.003 and p = 0.071, respectively) in steers treated with silymarin. Alanine aminotransferase activity was lower (p<0.06) for licorice and silymarin compared with the control group. There were no alterations in serum aspartate aminotransferase and gamma glutamyltransferase activities as a consequence of herb treatments (p = 0.203 and 0.135, respectively). Final body weight, body weight gain, average dairy gain and dry matter intake were not significantly different among treatments. Yield grade, marbling score and quality grade were higher for silymarin group than those of the control group (p<0.05). Therefore, the results suggest that silymarin can be used an effective dietary supplement as an alternative to antibiotic feed additive and a productivity enhancer, providing safe and more consumer acceptable alternative to synthetic compounds during the late fattening period of steers.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.858-879
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• 2009

Objectives : The object of this study was to investigate the effects of Daeboeum-hwan (DBEH) aqueous extracts on Streptozotocin (STZ)-induced rat diabetes and related complications. Methods : SD rats were divided into 6 groups (n =8) : 50 mM citrate buffer and vehicle (distilled water 5 ml/kg) administered group (Intact control), STZ treatment (60 mg/kg, single intraperitoneally administered) and vehicle administered group (STZ control), STZ treatment and silymarin 100 mg/kg administered group (Reference), and STZ treatment and DBEH extracts 50, 100 and 200 mg/kg administered groups. DBEH extracts were orally administered once a day for 28 days from 3 weeks after STZ treatment. The results were compared with silymarin 100 mg/kg. Results : Decreases in the body weights, increase of kidney and liver weights, blood glucose, BUN, creatinine, AST, ALT, LDL, triglyceride and total cholesterol levels with decreases of HD L levels, increases of pancreatic MDA contents and decreases of GSH contents were detected in STZ control as compared with intact control. These diabetes and related complications were inhibited by treatment with 100 and 200 mg/kg of DBEH extracts. Conclusion : DBEH extracts showed favorable effects on STZ-induced diabetes and related complications mediated by their antioxidant effects as similar to silymarin. Because the lowest dosage (50 mg/kg) of DBEH treated group did not show any favorable effects as compared with STZ control, the effective dosages of DBEH is considered as about 100 mg/kg, while DBEH extracts at 200 mg/kg showed similar effects as compared with 100 mg/kg of silymarin. It, therefore, is expected that DBEH will show favorable effects on diabetes and various diabetic complications.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.117-124
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• 2017

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interferon (IFN)-${\gamma}$, and interleukin (IL)-$1{\beta}$] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-${\alpha}$; 5 ng/ml, IFN-${\gamma}$; 5 ng/ml, and IL-$1{\beta}$; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

• YAKHAK HOEJI
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• v.38 no.6
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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.

• Natural Product Sciences
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• v.24 no.2
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• pp.82-87
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• 2018

Silymarin is the standardized extract from Silybum marianum which consists mainly of flavonoids and polyphenols. It is highly regarded for its hepatoprotective ability. Silybin B is a flavonolignan and one of the active components of silymarin. The content of silybin B in various parts of S. marianum was analyzed by HPLC-UV. Results show that the extract of seeds contain the highest amount of silybin B (7.434 mg/g DW). The petioles of S. marianum showed a low content of silybin B. This study revealed that seeds of S. marianum contain high amount of silybin B and could be a good source of the compound.