• Title/Summary/Keyword: Silybum marianum

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Improved Dissolution Characteristics of Silymarin and Their Bioavailability in Human Volunteers

  • Kim, Jeong-Hoon;Jang, Sun-Woo;Bac, Woong-Tak;Kweon, Jong-Weon;Kim, Won-Bac;Yoon, Mi-Kyeong;Choi, Young-Wook
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.312.1-312.1
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    • 2003
  • Silybin is the main component of Cardus marianus extracts (Silymarin) originated from Silybum marianum, called as milk thistle. It has a hepato-protective effect and is used clinically for the treatment of liver disease. But it is water-insoluble and is poorly absorbed from the gastrointestinal tract, resulting in very low oral bioavailability. Polymeric mixed-micelle precursor formulation containing surfactants, co-solvents, and block-co polymers with Cardus marianus extracts was made to enhance the dissolution rate of silybin and encapsulated with soft gelatin capsule. (omitted)

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Anti-oxidative Activities of Commercial Edible Plant Extracts Distributed in Korea (국내 유통 중인 식용식물 추출물의 항산화효과)

  • Kim, Kyung-Bum;Yoo, Ki-Hwan;Park, Ha-Yan;Jeong, Jong-Moon
    • Applied Biological Chemistry
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    • v.49 no.4
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    • pp.328-333
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    • 2006
  • Many plant extracts are known to have antioxidative effects. However, their activities can be reduced or disappeared during mass production process. The purpose of this study is to compare antioxidative effects of edible plant extracts distributed in Korea. forty three kinds of edible plant extracts commercially available in Korea were selected and investigated for their total phenolics contents and antioxidative potentials(DPPH radical and superoxide anion radical scavenging activities). In contents of total phenolics, the commercial plant extracts from Artemisia annua(whole plant), Ilex paraguariensis(leaf, Silybum marianum(fruit and leaf, Ulmus pumila(bark), Coliolus versicolor(fruit), and Curcuma longa(root and stem) contained over 70 mg/g of powder, DPPH radical scavenging activities($SC_{50}$, 50% scavenging concentration) of A. annua, I. paraguariensis, Pinus densiflora(leaf),S. marianum, U. pumila, and C. longa were $53.96{\pm}0.81\;ppm,\;24.61{\pm}2.12\;ppm,\;35.96{\pm}1.11\;ppm,\;57.46{\pm}2.13\;ppm,\;55.25{\pm}1.65\;ppm\;and\;12.99{\pm}1.67ppm$, respectively, while that of positive control(vitamin C) was $3.86{\pm}0.81\;ppm$. $SC_{50}$ values against superoxide anion radical of A. annua, Cinnamomum zeylanicum(bark), I. paraguariensis, Rubus coreanus(fruit and leaf), Morus alba(leaf), P. densiflora, S. marianum, U. pumila, C. versicolor, C. longa, Perilla frutescens var. acuta(leaf), and H. sabdariffa(leaf and newer) were $53.21{\pm}1.83ppm,\;50.12{\pm}2.12ppm,\;5.59{\pm}0.84ppm,\;41.60{\pm}8.93ppm,\;20.19{\pm}0.97ppm,\;15.19{\pm}1.66ppm,\;21.20{\pm}1.88ppm,\;15.71{\pm}0.91ppm,\;55.48{\pm}2.42ppm,\;52.12{\pm}2.44ppm,\;23.80{\pm}1.98ppm\;and\;11.14{\pm}0.51ppm$, respectively($SC_{50}$ value of vitamin C: $9.61{\pm}0.93ppm$). In particular, both 1 paraguariensis and P. densiflora had high content of phenolics as well as high scavenging activities of DPPH radical and superoxide anion radical. Consequently, above two commercial extracts may be useful as a source of antioxidative nutraceutics.

Reactive Oxygen Species Depletion by Silibinin Stimulates Apoptosis-Like Death in Escherichia coli

  • Lee, Bin;Lee, Dong Gun
    • Journal of Microbiology and Biotechnology
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    • v.27 no.12
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    • pp.2129-2140
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    • 2017
  • Silibinin is the major active component of silymarin, extracted from the medicinal plant Silybum marianum. Silibinin has potent antibacterial activity; however, the exact mechanism underlying its activity has not been elucidated. Here, we investigated the novel mechanism of silibinin against Escherichia coli. Time-kill kinetic assay showed that silibinin possess a bactericidal effect at minimal inhibitory concentration (MIC) and higher concentrations (2-and 4-fold MIC). At the membrane, depolarization and increased intracellular $Ca^{2+}$ levels were observed, considered as characteristics of bacterial apoptosis. Additionally, cells treated with MIC and higher concentrations showed apoptotic features like DNA fragmentation, phosphatidylserine exposure, and caspase-like protein expression. Generally, apoptotic death is closely related with ROS generation; however, silibinin did not induce ROS generation but acted as a scavenger of intracellular ROS. These results indicate that silibinin dose-dependently induces bacterial apoptosis-like death, which was affected by ROS depletion, suggesting that silibinin is a potential candidate for controlling bacteria.

Inhibition of Wnt Signaling by Silymarin in Human Colorectal Cancer Cells

  • Eo, Hyun Ji;Park, Gwang Hun;Jeong, Jin Boo
    • Biomolecules & Therapeutics
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    • v.24 no.4
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    • pp.380-386
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    • 2016
  • Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-${\kappa}B$-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of ${\beta}$-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular ${\beta}$-catenin protein but not mRNA. The inhibition of proteasome by MG132 and $GSK3{\beta}$ inhibition by SB216763 blocked silymarin-mediated downregulation of ${\beta}$-catenin. In addition, silymarin increased phosphorylation of ${\beta}$-catenin and a point mutation of S33Y attenuated silymarin-mediated ${\beta}$-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of ${\beta}$-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.

Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway

  • Kim, Eun Jeong;Kim, Jeeho;Lee, Min Young;Sudhanva, Muddenahalli Srinivasa;Devakumar, Sundaravinayagam;Jeon, Young Jin
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.282-287
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    • 2014
  • We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced production of nitric oxide (NO) in the pancreatic beta cell line MIN6N8a. Immunostaining and Western blot analysis showed that silymarin inhibits iNOS gene expression. RT-PCR showed that silymarin inhibits iNOS gene expression in a dose-dependent manner. We also showed that silymarin inhibits extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) phosphorylation. A MEK1 inhibitor abrogated CM-induced nitrite production, similar to silymarin. Treatment of MIN6N8a cells with silymarin also inhibited CM-stimulated activation of NF-${\kappa}B$, which is important for iNOS transcription. Collectively, we demonstrate that silymarin inhibits NO production in pancreatic beta cells, and silymarin may represent a useful anti-diabetic agent.

Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells

  • Youn, Cha Kyung;Park, Seon Joo;Lee, Min Young;Cha, Man Jin;Kim, Ok Hyeun;You, Ho Jin;Chang, In Youp;Yoon, Sang Pil;Jeon, Young Jin
    • Biomolecules & Therapeutics
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    • v.21 no.4
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    • pp.258-263
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    • 2013
  • We demonstrate herein that silibinin, a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), inhibits LPS-induced activation of macrophages and production of nitric oxide (NO) in RAW 264.7 cells. Western blot analysis showed silibinin inhibits iNOS gene expression. RT-PCR showed that silibinin inhibits iNOS, TNF-${\alpha}$, and $IL1{\beta}$. We also showed that silibinin strongly inhibits p38 MAPK phosphorylation, whereas the ERK1/2 and JNK pathways are not inhibited. The p38 MAPK inhibitor abrogated the LPS-induced nitrite production, whereas the MEK-1 inhibitor did not affect the nitrite production. A molecular modeling study proposed a binding pose for silibinin targeting the ATP binding site of p38 MAPK (1OUK). Collectively, this series of experiments indicates that silibinin inhibits macrophage activation by blocking p38 MAPK signaling.

Immunomodulatory effects of silymarin after subacute exposure to mice: A tiered approach immunotoxicity screening

  • Karimi, Gholamreza;Hassanzadeh-Josan, Samed;Memar, Bahram;Esmaeili, Seyed-Alireza;Riahi-Zanjani, Bamdad
    • Journal of Pharmacopuncture
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    • v.21 no.2
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    • pp.90-97
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    • 2018
  • Silymarin is a flavonoid complex extracted from the Silybum marianum plant with a wide range of pharmacological and biochemical effects. In the present study, the immunomodulatory effects of silymarin were investigated in BALB/c mice. Silymarin was administered daily by intraperitoneal injection at doses of 50, 100 and 150 mg/kg for 14 consecutive days. Following the exposure, host hematological parameters, spleen cellularity and histopathological examination, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), splenocyte cytokine production and lymphocyte proliferation assay were studied in all of the test groups of animals. The results showed that the low dose of silymarin (50 mg/kg) could stimulate both cellular and humoral immune functions in the treated hosts. In addition, silymarin at 100 mg/kg appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that silymarin has efficient immunostimulant properties. As a recommendation, the application of silymarin along with acupuncture technique (herbal acupuncture) can be thought as a good plan to modulate and enhance the immune system for the management of several immunodeficiency disorders. However, further studies are required to demonstrate this hypothesis.

Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by Blocking NF-${\kappa}B$ Pathway

  • Kim, Eun Jeong;Lee, Min Young;Jeon, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.3
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    • pp.211-218
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    • 2015
  • The present study showed that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced morphological changes in the mouse RAW264.7 macrophage cell line. We also showed that silymarin inhibited the nuclear translocation and transactivation activities of nuclear factor-kappa B (NF-${\kappa}B$), which is important for macrophage activation-associated changes in cell morphology and gene expression of inflammatory cytokines. BAY-11-7085, an NF-${\kappa}B$ inhibitor, abrogated LPS-induced morphological changes and NO production, similar to silymarin. Treatment of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). Collectively, these experiments demonstrated that silymarin inhibited LPS-induced morphological changes in the RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely mechanism underlying this biological effect involved inhibition of the MAPK pathway and NF-${\kappa}B$ activity. Inhibition of these activities by silymarin is a potentially useful strategy for the treatment of inflammation because of the critical roles played by MAPK and NF-${\kappa}B$ in mediating inflammatory responses in macrophages.

Clinical Pharmacokinetic Profiles of Hanmi SMEDDS Silymarin Soft Capsule Preparation (한미 SMEDDS 실리마린 연질캅셀 제제의 임상약동학적 특성)

  • 박민수;유내춘;김경환
    • 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 $T_{max}$./.>././.>./.

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Silibinin Inhibits Osteoclast Differentiation Mediated by TNF Family Members

  • Kim, Jung Ha;Kim, Kabsun;Jin, Hye Mi;Song, Insun;Youn, Bang Ung;Lee, Junwon;Kim, Nacksung
    • Molecules and Cells
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    • v.28 no.3
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    • pp.201-207
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    • 2009
  • Silibinin is a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), with known hepatoprotective, anticarcinogenic, and antioxidant effects. Herein, we show that silibinin inhibits receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced osteoclastogenesis from RAW264.7 cells as well as from bone marrow-derived monocyte/macrophage cells in a dose-dependent manner. Silibinin has no effect on the expression of RANKL or the soluble RANKL decoy receptor osteoprotegerin (OPG) in osteoblasts. However, we demonstrate that silibinin can block the activation of $NF-{\kappa}B$, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK) in osteoclast precursors in response to RANKL. Furthermore, silibinin attenuates the induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated receptor (OSCAR) expression during RANKL-induced osteoclastogenesis. We demonstrate that silibinin can inhibit $TNF-{\alpha}$-induced osteoclastogenesis as well as the expression of NFATc1 and OSCAR. Taken together, our results indicate that silibinin has the potential to inhibit osteoclast formation by attenuating the downstream signaling cascades associated with RANKL and $TNF-{\alpha}$.