• 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 $T_{max}$./.>././.>./.

• Journal of the East Asian Society of Dietary Life
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• v.23 no.6
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• pp.733-741
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• 2013

The objective of this study is to prepare functional beverages with dandelion (Taraxacum mongolicum H.) extracts. As a result of sensory evaluation, 10% water extracts of dandelion containing beverage, which was the highest value of overall preference, was chosen for further examinations. Moisture content of developed beverage was $99.6{\pm}0.5%$ and sugar content decreased from 0.8 to $0.7^{\circ}Brix$ whereas pH increased from 3.4 to 3.7 by addition of 10% dandelion extracts. Total phenolic and flavonoid contents of beverage were $295.8{\pm}5.8mg/L$ and $122.8{\pm}18.4mg/L$, respectively. The developed beverage showed higher DPPH radical scavenging activity of $98.2{\pm}0.6%$ than the beverage without extract. Moreover, concentration of silibinin in the T. mongolicum H. beverage was $0.3{\pm}0.04mg/L$.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.103.1-103.1
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• 2001

• YAKHAK HOEJI
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• v.58 no.1
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• pp.1-6
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• 2014

We examined whether silibinin and resveratrol affect airway mucin production, degradation of $I{\kappa}B$ and translocation of NF-${\kappa}B$ p65 induced by TNF-${\alpha}$ in NCI-H292 cells. Cells were pretreated with each agent for 30 min and then stimulated with TNF-${\alpha}$ for 24 h or the indicated periods. The two compounds suppressed TNF-${\alpha}$-induced airway mucin production, degradation of $I{\kappa}B$ and translocation of NF-${\kappa}B$ p65. This result suggests that silibinin and resveratrol can regulate the production of mucin induced by TNF-${\alpha}$ through the inactivation of NF-${\kappa}B$ pathway in airway epithelial cells.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.291-298
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• 2021

In this study, we investigated whether the combined administration of berberine (BBR) and silibinin (SBN) was effective in improving hyperlipidemia and anti-obesity efficacy using a high-fat diet (HFD)-fed obese mouse model. HFD-induced obese mice were supplemented with the BBR and SBN combination (BBR-SBN) along with the HFD administration for 8 weeks. During the experiment, body weight, food intake, and levels of total cholesterol, triglyceride and high-density lipoprotein (HDL)-cholesterol were analyzed. Consumption of HFD in the mice caused rapid increases in body weight and the levels of total cholesterol and triglycerides compared to the normal control (NC) group. However, supplementation of BBR-SBN in these obese mice significantly reduced body weight gain and suppressed the levels of total cholesterol and triglyceride with the increment of HDL cholesterol level. In the HFD-fed group, abdominal fat weight was significantly increased and the adipocytes within the epididymal adipose tissue were found to have expanded sizes compared to the NC group. However, in the BBR-SBN group, the sizes of the adipocytes were comparable to those of the NC group and abdominal fat weight was significantly reduced. Moreover, the deposition of giant vesicular fat cells in liver tissues seen in the HFD-fed group was considerably reduced in the BBR-SBN group. These results suggest that the BBR-SBN combination tends to have synergic potential as an anti-obesity agent by significantly reducing body weight gain as well as lowering serum lipid levels and thus improving anti-obesity efficacy in HFD-induced obese mice.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.281.1-281.1
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• 2001

• Archives of Pharmacal Research
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• v.27 no.6
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• pp.600-603
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• 2004

(＋）-Dehydrovomifoliol (1）. 3-hydroxy-5$\alpha$,6$\alpha$-epoxy-$\beta$-ionone (2）, vitexin 7 -O-$\beta$-D-glucopyrano-side (3）, and vitexin 2'-O-$\beta$-D-glucopyranoside (4） were isolated as new constituents from the aerial parts of Beta vulgaris var. cicla. Compounds 3 and 4 demonstrated hepatoprotective activity with values of 65.8 and 56.1％, respectively, in primary cultured rat hepatocytes with $CCl_4$-induced cell toxicity, compared to controls. This was comparable to that of silibinin (69.8％） which was used as a positive control.trol.

• Journal of The Korean Society of Clinical Toxicology
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• v.16 no.1
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• pp.33-41
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• 2018

Purpose: This study was conducted to evaluate the clinical efficacy of pharmacologic treatment of amatoxin poisoning patients. Methods: Literature was accessed through PubMed, EMBASE, Cochrane library, KoreaMed, KISS and KMBASE. Studies relevant to human use of pharmacologic therapy including silymarin, penicillin and N-acetylcysteine (NAC) for amanita poisoning were included. Case reports, letters, editorials and papers with insufficient information were excluded. Comparison of clinical outcomes (especially mortality and liver transplantation rate) in each study was analyzed. Results: The final analysis included 13 retrospective studies. None of these studies showed direct comparisons of individual agents. Among 12 studies comparing silymarin vs penicillin, eight showed clinical superiority of silymarin. Among eight studies comparing silymarin with NAC, six showed clinical superiority of silymarin. Among seven studies of NAC vs penicillin, five showed clinical superiority of NAC. Conclusion: This systematic review suggested that clinical superiority of various pharmacological agents used to treat amatoxin poisoning is debatable. Nevertheless, the available evidence suggests it is reasonable to consider combinations of multiple agents for patients with amanita poisoning. Further studies are required to establish a treatment regimen for amanita poisoning.

• Journal of The Korean Society of Clinical Toxicology
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• v.16 no.2
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• pp.108-115
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• 2018

Purpose: Glehnia littoralis has been reported to have several pharmacological properties but no in vivo reports describing the protective effects of this plant on${\alpha}$-amanitin-induced hepatotoxicity have been published. ${\alpha}$-Amanitin is a peptide found in several mushroom species that accounts for the majority of severe mushroom poisonings leading to severe hepatonecrosis. In our previous in vitro study, we found that ${\alpha}$-amanitin induced oxidative stress, which may contribute to its severe hepatotoxicity. The aim of this study was to investigate whether Glehnia littoralis acetate extract (GLEA) has protective antioxidant effects on ${\alpha}$-amanitin-induced hepatotoxicity in a murine model. Methods: Swiss mice (n=40 in all groups) were divided into four groups (n=10/group). Three hours after giving ${\alpha}$-amanitin (0.6 mg/kg, i.p.) to the mice, they were administered silibinin (50 mg/kg/d, i.p.) or Glehnia littoralis ethyl acetate extract (100 mg/kg/d, oral) therapies once a day for 3 days. After 72 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurement, and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was assessed by a pathologist blinded to the treatment group and divided into 4 categories according to the grade of hepatonecrosis. Results: GLEA significantly improved the beneficial functional parameters in ${\alpha}$-amanitin-induced hepatotoxicity. In the histopathological evaluation, the toxicity that was generated with ${\alpha}$-amanitin was significantly reduced by GLEA, showing a possible hepatoprotective effect. Conclusion: In this murine model, Glehnia littoralis was effective in limiting hepatic injury after ${\alpha}$-amanitin poisoning. Increases of aminotransferases and degrees of hepatonecrosis were attenuated by this antidotal therapy.

• Journal of The Korean Society of Clinical Toxicology
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• v.17 no.2
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• pp.58-65
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• 2019

Purpose: Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms of α-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo. Methods: The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated. Results: In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used. Conclusion: GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.