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Medical Forum / Diseases and Disorders / Hepatitis / April 2009Anti-inflammatory Anti-fibrogenic Iron-chelating Silybin
Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells Marco Trappoliere1, Alessandra Caligiuri1, Monika Schmid1, Cristiana Bertolani1, Paola Failli2, Francesco Vizzutti1, Erica Novo3, Carlo di Manzano4, Fabio Marra1, 6, Carmela Loguercio5 and Massimo Pinzani1, 6, , 1Dipartimento di Medicina Interna, Università degli Studi di Firenze, Viale G.B. Morgagni, 85, 50134 Florence, Italy 2Dipartimento di Farmacologia Preclinica e Clinica, Università degli Studi di Firenze, Florence, Italy 3Dipartimento di Medicina e Oncologia Sperimentale, Università degli Studi di Torino, Turin, Italy 4IBI Istituto Biochimico Italiano Giovanni Lorenzini, Seconda Università di Napoli, Naples, Italy 5Dipartimento di Gastroenterologia, Seconda Università di Napoli, Naples, Italy 6Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy Received 25 July 2008; revised 19 December 2008; accepted 4 February 2009. Associate Editor: A. Geerts. Available online 5 April 2009. Background/Aims Hepatic fibrogenesis, a consequence of chronic liver tissue damage, is characterized by activation of the hepatic stellate cells (HSC). Silybin has been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the fine cellular and molecular events responsible for this effect. The aim of this study was to assess the mechanisms regulating the anti-fibrogenic and anti-inflammatory activity of Silybin. Methods Human HSC were cultured on plastic and their activations and related signalling were studied. Results Silybin was able to inhibit dose-dependently (25–50 μM) growth factor-induced pro-fibrogenic actions of activated human HSC, including cell proliferation (P < 0.001), cell motility (P < 0.001), and de novo synthesis of extracellular matrix components (P < 0.05). Silybin (25–50 μM)), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01) and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkBα phosphorylation. In addition, Silybin was confirmed to act as a potent anti-oxidant agent. Conclusion The results of the study provide molecular insights into the potential therapeutic action of Silybin in chronic liver disease. This action seems to be mostly related to a marked inhibition of the production of pro-inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct and indirect pro-fibrogenic potential of HSC. Keywords: Silybin; Hepatic inflammation; Fibrogenesis Abbreviations: CLD, chronic liver disease; DMNQ, 2,3-dimethoxy-1- naphthoquinone; ECM, extracellular matrix; HSC, hepatic stellate cells; H2O2, hydrogen peroxide; IL, interleukin; [Ca2+]i, intracellular free calcium concentration; [3H]TdR, methyl-[3H] thymidine; MCP-1, monocyte chemoattractant protein-1; PDGF, platelet- derived growth factor; SFIF, serum-free/insulin-free; TGF-β-1, transforming growth factor-β1; X/XO, xanthine/xanthine oxidase ---------------- Silybin, a new iron-chelating agent. J Inorg Biochem. 2001 Jun;85(2-3):123-9. Borsari M, Gabbi C, Ghelfi F, Grandi R, Saladini M, Severi S, Borella F. Dipartimento di Chimica, Università di Modena, Via Campi 183-41100 Modena, Italy. Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. PMID: 11410232 -------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk I(O O)I (o) On Apr 7, 5:43 pm, Ken <flakey...@earthlink.net> wrote:snip << Remember as you cut this post .. it is evidence of the dysfunctional predatorial nature of yours VERY common in men who prefer to have sex with boys .. http://www.traditionalvalues.org/homosexual_movement_and_pedophilia/ http://www.talk2action.org/story/2006/10/3/21245/3789 http://predatorsafety.blogspot.com/2008/11/homosexual-grooming-of-chi... Predator Safety - Dedicated To The Protection Of Our Children All posts made by .. ken .. evidence .. mental instability .. common to homosexuals .. IE: "Dysfunctional Homosexuals" I(O O)I (0) On Apr 7, 7:41 pm, Ken <flakey...@earthlink.net> wrote: snip << Remember as you cut this post .. it is evidence of the dysfunctional predatorial nature of yours VERY common in men who prefer to have sex with boys .. http://www.traditionalvalues.org/homosexual_movement_and_pedophilia/ http://www.talk2action.org/story/2006/10/3/21245/3789 http://predatorsafety.blogspot.com/2008/11/homosexual-grooming-of-chi... Predator Safety - Dedicated To The Protection Of Our Children All posts made by .. ken .. evidence .. mental instability .. common to homosexuals .. IE: "Dysfunctional Homosexuals" Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells Marco Trappoliere1, Alessandra Caligiuri1, Monika Schmid1, Cristiana Bertolani1, Paola Failli2, Francesco Vizzutti1, Erica Novo3, Carlo di Manzano4, Fabio Marra1, 6, Carmela Loguercio5 and Massimo Pinzani1, 6, , 1Dipartimento di Medicina Interna, Universit¨¤ degli Studi di Firenze, Viale G.B. Morgagni, 85, 50134 Florence, Italy 2Dipartimento di Farmacologia Preclinica e Clinica, Universit¨¤ degli Studi di Firenze, Florence, Italy 3Dipartimento di Medicina e Oncologia Sperimentale, Universit¨¤ degli Studi di Torino, Turin, Italy 4IBI Istituto Biochimico Italiano Giovanni Lorenzini, Seconda Universit¨¤ di Napoli, Naples, Italy 5Dipartimento di Gastroenterologia, Seconda Universit¨¤ di Napoli, Naples, Italy 6Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy Received 25 July 2008; revised 19 December 2008; accepted 4 February 2009. Associate Editor: A. Geerts. Available online 5 April 2009. Background/Aims Hepatic fibrogenesis, a consequence of chronic liver tissue damage, is characterized by activation of the hepatic stellate cells (HSC). Silybin has been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the fine cellular and molecular events responsible for this effect. The aim of this study was to assess the mechanisms regulating the anti-fibrogenic and anti-inflammatory activity of Silybin. Methods Human HSC were cultured on plastic and their activations and related signalling were studied. Results Silybin was able to inhibit dose-dependently (25¨C50 ¦ÌM) growth factor-induced pro-fibrogenic actions of activated human HSC, including cell proliferation (P < 0.001), cell motility (P < 0.001), and de novo synthesis of extracellular matrix components (P < 0.05). Silybin (25¨C50 ¦ÌM)), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01) and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkB¦Á phosphorylation. In addition, Silybin was confirmed to act as a potent anti-oxidant agent. Conclusion The results of the study provide molecular insights into the potential therapeutic action of Silybin in chronic liver disease. This action seems to be mostly related to a marked inhibition of the production of pro-inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct and indirect pro-fibrogenic potential of HSC. Keywords: Silybin; Hepatic inflammation; Fibrogenesis Abbreviations: CLD, chronic liver disease; DMNQ, 2,3-dimethoxy-1- naphthoquinone; ECM, extracellular matrix; HSC, hepatic stellate cells; H2O2, hydrogen peroxide; IL, interleukin; [Ca2+]i, intracellular free calcium concentration; [3H]TdR, methyl-[3H] thymidine; MCP-1, monocyte chemoattractant protein-1; PDGF, platelet- derived growth factor; SFIF, serum-free/insulin-free; TGF-¦Â-1, transforming growth factor-¦Â1; X/XO, xanthine/xanthine oxidase ---------------- Silybin, a new iron-chelating agent. J Inorg Biochem. 2001 Jun;85(2-3):123-9. Borsari M, Gabbi C, Ghelfi F, Grandi R, Saladini M, Severi S, Borella F. Dipartimento di Chimica, Universit¨¤ di Modena, Via Campi 183-41100 Modena, Italy. Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. PMID: 11410232 -------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk On Apr 7, 5:43 pm, Ken <flakey...@earthlink.net> wrote:snip << Remember as you cut this post .. it is evidence of the dysfunctional predatorial nature of yours VERY common in men who prefer to have sex with boys .. http://www.traditionalvalues.org/homosexual_movement_and_pedophilia/ http://www.talk2action.org/story/2006/10/3/21245/3789 http://predatorsafety.blogspot.com/2008/11/homosexual-grooming-of-chi... Predator Safety - Dedicated To The Protection Of Our Children All posts made by .. ken .. evidence .. mental instability .. common to homosexuals .. IE: "Dysfunctional Homosexuals" Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells Marco Trappoliere1, Alessandra Caligiuri1, Monika Schmid1, Cristiana Bertolani1, Paola Failli2, Francesco Vizzutti1, Erica Novo3, Carlo di Manzano4, Fabio Marra1, 6, Carmela Loguercio5 and Massimo Pinzani1, 6, , 1Dipartimento di Medicina Interna, Universit¨¤ degli Studi di Firenze, Viale G.B. Morgagni, 85, 50134 Florence, Italy 2Dipartimento di Farmacologia Preclinica e Clinica, Universit¨¤ degli Studi di Firenze, Florence, Italy 3Dipartimento di Medicina e Oncologia Sperimentale, Universit¨¤ degli Studi di Torino, Turin, Italy 4IBI Istituto Biochimico Italiano Giovanni Lorenzini, Seconda Universit¨¤ di Napoli, Naples, Italy 5Dipartimento di Gastroenterologia, Seconda Universit¨¤ di Napoli, Naples, Italy 6Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy Received 25 July 2008; revised 19 December 2008; accepted 4 February 2009. Associate Editor: A. Geerts. Available online 5 April 2009. Background/Aims Hepatic fibrogenesis, a consequence of chronic liver tissue damage, is characterized by activation of the hepatic stellate cells (HSC). Silybin has been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the fine cellular and molecular events responsible for this effect. The aim of this study was to assess the mechanisms regulating the anti-fibrogenic and anti-inflammatory activity of Silybin. Methods Human HSC were cultured on plastic and their activations and related signalling were studied. Results Silybin was able to inhibit dose-dependently (25¨C50 ¦ÌM) growth factor-induced pro-fibrogenic actions of activated human HSC, including cell proliferation (P < 0.001), cell motility (P < 0.001), and de novo synthesis of extracellular matrix components (P < 0.05). Silybin (25¨C50 ¦ÌM)), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01) and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkB¦Á phosphorylation. In addition, Silybin was confirmed to act as a potent anti-oxidant agent. Conclusion The results of the study provide molecular insights into the potential therapeutic action of Silybin in chronic liver disease. This action seems to be mostly related to a marked inhibition of the production of pro-inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct and indirect pro-fibrogenic potential of HSC. Keywords: Silybin; Hepatic inflammation; Fibrogenesis Abbreviations: CLD, chronic liver disease; DMNQ, 2,3-dimethoxy-1- naphthoquinone; ECM, extracellular matrix; HSC, hepatic stellate cells; H2O2, hydrogen peroxide; IL, interleukin; [Ca2+]i, intracellular free calcium concentration; [3H]TdR, methyl-[3H] thymidine; MCP-1, monocyte chemoattractant protein-1; PDGF, platelet- derived growth factor; SFIF, serum-free/insulin-free; TGF-¦Â-1, transforming growth factor-¦Â1; X/XO, xanthine/xanthine oxidase ---------------- Silybin, a new iron-chelating agent. J Inorg Biochem. 2001 Jun;85(2-3):123-9. Borsari M, Gabbi C, Ghelfi F, Grandi R, Saladini M, Severi S, Borella F. Dipartimento di Chimica, Universit¨¤ di Modena, Via Campi 183-41100 Modena, Italy. Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. PMID: 11410232 -------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > I(O O)I > (o) He's talking about milk thistle, Ken. Although there are no definitive ties between the benefits and HCV victims (although milk thistle is known to be beneficial to the liver), I and a lot of others take it. Let it go. >> I(O O)I >> (o) > > He's talking about milk thistle, Ken. Although there are no definitive > ties between the benefits and HCV victims (although milk thistle is known > to be beneficial to the liver), I and a lot of others take it. Let it go. //////////////////////////////////////////////// Milk Thistle derivative (for slides, join CCO and click on link, at bottom of this extract) all non-alt.support.hepatitis-c addresses removed to reduce goofs - Cactus Jammies Abbreviations and acronyms Silibinin IV, intravenously; pegIFN, peginterferon alfa; PO, orally; RBV, ribavirin; TID, twice daily. Ferenci and colleagues presented a very interesting and provocative study that evaluated the use of silibinin in combination with peginterferon alfa and ribavirin among previous peginterferon alfa and ribavirin nonresponders. Silibinin is the major active isomer of silymarin or milk thistle. It is the active component that is thought to provide much of the antioxidant effect of silymarin. There is significant debate as to whether silibinin is associated with any antiviral efficacy. In this study, it was hypothesized that intravenous silibinin would have potential antiviral activity against HCV. The study design is illustrated in this slide. A total of 20 peginterferon alfa and ribavirin nonresponders were randomized to receive 1 of 4 different weight-based intravenous infusions of silibinin daily for 1 week. The doses were 5 mg/kg/day, 10 mg/kg/day, 15 mg/kg/day, and 20 mg/kg/day. The majority of the patient population was infected with genotype 1 HCV, and 7 of the patients had significant fibrosis. Thirteen of the patients previously achieved < 2 log10 IU/mL reduction in HCV RNA on peginterferon alfa and ribavirin treatment, and all of the patients had detectable HCV RNA at Week 24 of previous therapy. After Week 1, patients continued silibinin and initiated peginterferon alfa and ribavirin. After Week 2, patients were switched from intravenous silibinin to oral silymarin 280 mg, 3 times daily, in combination with peginterferon alfa and ribavirin for a total of 13 weeks. This slide illustrates the interim results achieved with the use of silibinin in combination with peginterferon alfa and ribavirin. The blue columns represent the results following 1 week of silibinin monotherapy. There was a dose-dependent increase in the HCV RNA decline from baseline following 1 week of intravenous silibinin. Patients who received silibinin 20 mg/kg/day achieved nearly a 4 log10 IU/mL reduction in HCV RNA compared with the 0.5 log10 IU/mL reduction achieved in the silibinin 5 mg/kg/day group. The orange columns represent the decline in HCV RNA from baseline following the addition of peginterferon alfa and ribavirin at Week 2 of treatment. There was an incremental decrease in HCV RNA among patients who received silibinin 10 mg/kg/day, 15 mg/kg/day, and 20 mg/kg/day. In fact, 2 patients in the silibinin 15 mg/kg/day arm and 4 patients in the silibinin 20 mg/kg/day arm achieved undetectable HCV RNA. These findings are surprising and strongly suggestive that there is a direct antiviral effect associated with the use of intravenous silibinin. However, further evaluation is clearly needed. Obviously, one of the issues concerns the use of intravenous, high-dose, purified silibinin rather than standard, oral silymarin. The intravenous administration assured high concentrations of the drug in these patients. Although this study is provocative, further validation is required to determine whether there is a potential for this type of therapy with milk thistle in HCV-infected patients. For more information, go online to: http://clinicaloptions.com/Hepatitis/Conference%20Coverage/Milan%202008/Tracks/I nvestigational%20HCV/Capsules/63.aspx >Silybin, a component of sylimarin, exerts anti-inflammatory >and anti-fibrogenic effects on human hepatic stellate cells [quoted text clipped - 114 lines] >DEAD PEOPLE WALKING >http://tinyurl.com/zk9fk On Apr 8, 7:39 am, The Good Rev Dr Heretic PhD <Rev_Dr_Here...@athiest.va> wrote: snip << I before e except after .. c .. Write it down .. The rules in the groups .. the sci groups .. are .. You MUST contribute something to the groups BEFORE you post to **any** threads .. YOU have contributed nothing .. You have only been here for a couple of weeks and have not had the time TO contribute .. ? Contribute something to the sci .. groups .. THEN you are allowed to post .. Did I explain it well enough for ya .. atheist .. Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells Marco Trappoliere1, Alessandra Caligiuri1, Monika Schmid1, Cristiana Bertolani1, Paola Failli2, Francesco Vizzutti1, Erica Novo3, Carlo di Manzano4, Fabio Marra1, 6, Carmela Loguercio5 and Massimo Pinzani1, 6, , 1Dipartimento di Medicina Interna, Universit¨¤ degli Studi di Firenze, Viale G.B. Morgagni, 85, 50134 Florence, Italy 2Dipartimento di Farmacologia Preclinica e Clinica, Universit¨¤ degli Studi di Firenze, Florence, Italy 3Dipartimento di Medicina e Oncologia Sperimentale, Universit¨¤ degli Studi di Torino, Turin, Italy 4IBI Istituto Biochimico Italiano Giovanni Lorenzini, Seconda Universit¨¤ di Napoli, Naples, Italy 5Dipartimento di Gastroenterologia, Seconda Universit¨¤ di Napoli, Naples, Italy 6Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy Received 25 July 2008; revised 19 December 2008; accepted 4 February 2009. Associate Editor: A. Geerts. Available online 5 April 2009. Background/Aims Hepatic fibrogenesis, a consequence of chronic liver tissue damage, is characterized by activation of the hepatic stellate cells (HSC). Silybin has been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the fine cellular and molecular events responsible for this effect. The aim of this study was to assess the mechanisms regulating the anti-fibrogenic and anti-inflammatory activity of Silybin. Methods Human HSC were cultured on plastic and their activations and related signalling were studied. Results Silybin was able to inhibit dose-dependently (25¨C50 ¦ÌM) growth factor-induced pro-fibrogenic actions of activated human HSC, including cell proliferation (P < 0.001), cell motility (P < 0.001), and de novo synthesis of extracellular matrix components (P < 0.05). Silybin (25¨C50 ¦ÌM)), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01) and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkB¦Á phosphorylation. In addition, Silybin was confirmed to act as a potent anti-oxidant agent. Conclusion The results of the study provide molecular insights into the potential therapeutic action of Silybin in chronic liver disease. This action seems to be mostly related to a marked inhibition of the production of pro-inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct and indirect pro-fibrogenic potential of HSC. Keywords: Silybin; Hepatic inflammation; Fibrogenesis Abbreviations: CLD, chronic liver disease; DMNQ, 2,3-dimethoxy-1- naphthoquinone; ECM, extracellular matrix; HSC, hepatic stellate cells; H2O2, hydrogen peroxide; IL, interleukin; [Ca2+]i, intracellular free calcium concentration; [3H]TdR, methyl-[3H] thymidine; MCP-1, monocyte chemoattractant protein-1; PDGF, platelet- derived growth factor; SFIF, serum-free/insulin-free; TGF-¦Â-1, transforming growth factor-¦Â1; X/XO, xanthine/xanthine oxidase ---------------- Silybin, a new iron-chelating agent. J Inorg Biochem. 2001 Jun;85(2-3):123-9. Borsari M, Gabbi C, Ghelfi F, Grandi R, Saladini M, Severi S, Borella F. Dipartimento di Chimica, Universit¨¤ di Modena, Via Campi 183-41100 Modena, Italy. Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. PMID: 11410232 -------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk On Apr 8, 7:39 am, The Good Rev Dr Heretic PhD <Rev_Dr_Here...@athiest.va> wrote: snip << Take it easy, I.J. No sense in getting worked up. He's just goading you. II(O O)II (o) > You MUST contribute something to the groups BEFORE you post to **any** > threads .. > On Apr 8, 7:39 am, The Good Rev Dr Heretic PhD > [quoted text clipped - 136 lines] > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk > > You MUST contribute something to the groups BEFORE you post to **any** > > threads .. It's called BS and Rusty the 'Tard's full o' it Indeed, Rusty is correct on that. Anyone that feels that Tom has not contributed needs to pay closer attention to the posts. He has done an excellent job of showing how iron deficiency can cause obvious cognitive dysfunction, even to the point of stammering on his keyboard. Anybody that thinks Rusty doesn't contribute, count the periods. > On Apr 8, 7:39 am, The Good Rev Dr Heretic PhD > [quoted text clipped - 10 lines] > > YOU have contributed nothing .. Shteaters congregating again .. You were told no more than two of you shteaters because it breaks the law. You are abnormal and collude to commit unspeakable acts. Remember you shteaters when you cut my posts .. it is evidence of the dysfunctional predatorial nature of yours VERY common in men who prefer to have sex with boys .. http://www.traditionalvalues.org/homosexual_movement_and_pedophilia/ http://www.talk2action.org/story/2006/10/3/21245/3789 http://predatorsafety.blogspot.com/2008/11/homosexual-grooming-of-chi... Predator Safety - Dedicated To The Protection Of Our Children The previous posts by the shteaters in this thread .. evidence .. mental instability .. common to homosexuals .. IE: "Dysfunctional Homosexuals" Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells Marco Trappoliere1, Alessandra Caligiuri1, Monika Schmid1, Cristiana Bertolani1, Paola Failli2, Francesco Vizzutti1, Erica Novo3, Carlo di Manzano4, Fabio Marra1, 6, Carmela Loguercio5 and Massimo Pinzani1, 6, , 1Dipartimento di Medicina Interna, Universit¨¤ degli Studi di Firenze, Viale G.B. Morgagni, 85, 50134 Florence, Italy 2Dipartimento di Farmacologia Preclinica e Clinica, Universit¨¤ degli Studi di Firenze, Florence, Italy 3Dipartimento di Medicina e Oncologia Sperimentale, Universit¨¤ degli Studi di Torino, Turin, Italy 4IBI Istituto Biochimico Italiano Giovanni Lorenzini, Seconda Universit¨¤ di Napoli, Naples, Italy 5Dipartimento di Gastroenterologia, Seconda Universit¨¤ di Napoli, Naples, Italy 6Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy Received 25 July 2008; revised 19 December 2008; accepted 4 February 2009. Associate Editor: A. Geerts. Available online 5 April 2009. Background/Aims Hepatic fibrogenesis, a consequence of chronic liver tissue damage, is characterized by activation of the hepatic stellate cells (HSC). Silybin has been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the fine cellular and molecular events responsible for this effect. The aim of this study was to assess the mechanisms regulating the anti-fibrogenic and anti-inflammatory activity of Silybin. Methods Human HSC were cultured on plastic and their activations and related signalling were studied. Results Silybin was able to inhibit dose-dependently (25¨C50 ¦ÌM) growth factor-induced pro-fibrogenic actions of activated human HSC, including cell proliferation (P < 0.001), cell motility (P < 0.001), and de novo synthesis of extracellular matrix components (P < 0.05). Silybin (25¨C50 ¦ÌM)), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01) and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkB¦Á phosphorylation. In addition, Silybin was confirmed to act as a potent anti-oxidant agent. Conclusion The results of the study provide molecular insights into the potential therapeutic action of Silybin in chronic liver disease. This action seems to be mostly related to a marked inhibition of the production of pro-inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct and indirect pro-fibrogenic potential of HSC. Keywords: Silybin; Hepatic inflammation; Fibrogenesis Abbreviations: CLD, chronic liver disease; DMNQ, 2,3-dimethoxy-1- naphthoquinone; ECM, extracellular matrix; HSC, hepatic stellate cells; H2O2, hydrogen peroxide; IL, interleukin; [Ca2+]i, intracellular free calcium concentration; [3H]TdR, methyl-[3H] thymidine; MCP-1, monocyte chemoattractant protein-1; PDGF, platelet- derived growth factor; SFIF, serum-free/insulin-free; TGF-¦Â-1, transforming growth factor-¦Â1; X/XO, xanthine/xanthine oxidase ---------------- Silybin, a new iron-chelating agent. J Inorg Biochem. 2001 Jun;85(2-3):123-9. Borsari M, Gabbi C, Ghelfi F, Grandi R, Saladini M, Severi S, Borella F. Dipartimento di Chimica, Universit¨¤ di Modena, Via Campi 183-41100 Modena, Italy. Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. PMID: 11410232 -------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk FOAD Troll On Apr 9, 5:28 pm, Ken <flakey...@aol.com> wrote: snip << Shteaters congregating again .. You were told no more than two of you shteaters because it breaks the law. You are abnormal and collude to commit unspeakable acts. Remember you shteaters when you cut my posts .. it is evidence of the dysfunctional predatorial nature of yours VERY common in men who prefer to have sex with boys .. http://www.traditionalvalues.org/homosexual_movement_and_pedophilia/ http://www.talk2action.org/story/2006/10/3/21245/3789 http://predatorsafety.blogspot.com/2008/11/homosexual-grooming-of-chi... Predator Safety - Dedicated To The Protection Of Our Children The previous posts by the shteaters in this thread .. evidence .. mental instability .. common to homosexuals .. IE: "Dysfunctional Homosexuals" Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells Marco Trappoliere1, Alessandra Caligiuri1, Monika Schmid1, Cristiana Bertolani1, Paola Failli2, Francesco Vizzutti1, Erica Novo3, Carlo di Manzano4, Fabio Marra1, 6, Carmela Loguercio5 and Massimo Pinzani1, 6, , 1Dipartimento di Medicina Interna, Universit¨¤ degli Studi di Firenze, Viale G.B. Morgagni, 85, 50134 Florence, Italy 2Dipartimento di Farmacologia Preclinica e Clinica, Universit¨¤ degli Studi di Firenze, Florence, Italy 3Dipartimento di Medicina e Oncologia Sperimentale, Universit¨¤ degli Studi di Torino, Turin, Italy 4IBI Istituto Biochimico Italiano Giovanni Lorenzini, Seconda Universit¨¤ di Napoli, Naples, Italy 5Dipartimento di Gastroenterologia, Seconda Universit¨¤ di Napoli, Naples, Italy 6Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy Received 25 July 2008; revised 19 December 2008; accepted 4 February 2009. Associate Editor: A. Geerts. Available online 5 April 2009. Background/Aims Hepatic fibrogenesis, a consequence of chronic liver tissue damage, is characterized by activation of the hepatic stellate cells (HSC). Silybin has been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the fine cellular and molecular events responsible for this effect. The aim of this study was to assess the mechanisms regulating the anti-fibrogenic and anti-inflammatory activity of Silybin. Methods Human HSC were cultured on plastic and their activations and related signalling were studied. Results Silybin was able to inhibit dose-dependently (25¨C50 ¦ÌM) growth factor-induced pro-fibrogenic actions of activated human HSC, including cell proliferation (P < 0.001), cell motility (P < 0.001), and de novo synthesis of extracellular matrix components (P < 0.05). Silybin (25¨C50 ¦ÌM)), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01) and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkB¦Á phosphorylation. In addition, Silybin was confirmed to act as a potent anti-oxidant agent. Conclusion The results of the study provide molecular insights into the potential therapeutic action of Silybin in chronic liver disease. This action seems to be mostly related to a marked inhibition of the production of pro-inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct and indirect pro-fibrogenic potential of HSC. Keywords: Silybin; Hepatic inflammation; Fibrogenesis Abbreviations: CLD, chronic liver disease; DMNQ, 2,3-dimethoxy-1- naphthoquinone; ECM, extracellular matrix; HSC, hepatic stellate cells; H2O2, hydrogen peroxide; IL, interleukin; [Ca2+]i, intracellular free calcium concentration; [3H]TdR, methyl-[3H] thymidine; MCP-1, monocyte chemoattractant protein-1; PDGF, platelet- derived growth factor; SFIF, serum-free/insulin-free; TGF-¦Â-1, transforming growth factor-¦Â1; X/XO, xanthine/xanthine oxidase ---------------- Silybin, a new iron-chelating agent. J Inorg Biochem. 2001 Jun;85(2-3):123-9. Borsari M, Gabbi C, Ghelfi F, Grandi R, Saladini M, Severi S, Borella F. Dipartimento di Chimica, Universit¨¤ di Modena, Via Campi 183-41100 Modena, Italy. Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. PMID: 11410232 -------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk From the Idjit Canuck Fool On Apr 10, 7:45 am, Ken <flakey...@aol.com> wrote: snip << Shteater .. You were told to take your useless shteating self somewhere .. else .. You are dysfunctional .. therefore not allowed in the groups .. Remember you shteaters when you cut my posts .. it is evidence of the dysfunctional predatorial nature of yours VERY common in men who prefer to have sex with boys .. http://www.traditionalvalues.org/homosexual_movement_and_pedophilia/ http://www.talk2action.org/story/2006/10/3/21245/3789 http://predatorsafety.blogspot.com/2008/11/homosexual-grooming-of-chi... Predator Safety - Dedicated To The Protection Of Our Children The previous posts by the shteaters in this thread .. evidence .. mental instability .. common to homosexuals .. IE: "Dysfunctional Homosexuals" Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells Marco Trappoliere1, Alessandra Caligiuri1, Monika Schmid1, Cristiana Bertolani1, Paola Failli2, Francesco Vizzutti1, Erica Novo3, Carlo di Manzano4, Fabio Marra1, 6, Carmela Loguercio5 and Massimo Pinzani1, 6, , 1Dipartimento di Medicina Interna, Universit¨¤ degli Studi di Firenze, Viale G.B. Morgagni, 85, 50134 Florence, Italy 2Dipartimento di Farmacologia Preclinica e Clinica, Universit¨¤ degli Studi di Firenze, Florence, Italy 3Dipartimento di Medicina e Oncologia Sperimentale, Universit¨¤ degli Studi di Torino, Turin, Italy 4IBI Istituto Biochimico Italiano Giovanni Lorenzini, Seconda Universit¨¤ di Napoli, Naples, Italy 5Dipartimento di Gastroenterologia, Seconda Universit¨¤ di Napoli, Naples, Italy 6Center for Research, High Education and Transfer DENOThe, University of Florence, Florence, Italy Received 25 July 2008; revised 19 December 2008; accepted 4 February 2009. Associate Editor: A. Geerts. Available online 5 April 2009. Background/Aims Hepatic fibrogenesis, a consequence of chronic liver tissue damage, is characterized by activation of the hepatic stellate cells (HSC). Silybin has been shown to exert anti-fibrogenic effects in animal models. However, scant information is available on the fine cellular and molecular events responsible for this effect. The aim of this study was to assess the mechanisms regulating the anti-fibrogenic and anti-inflammatory activity of Silybin. Methods Human HSC were cultured on plastic and their activations and related signalling were studied. Results Silybin was able to inhibit dose-dependently (25¨C50 ¦ÌM) growth factor-induced pro-fibrogenic actions of activated human HSC, including cell proliferation (P < 0.001), cell motility (P < 0.001), and de novo synthesis of extracellular matrix components (P < 0.05). Silybin (25¨C50 ¦ÌM)), inhibited the IL-1-induced synthesis of MCP-1 (P < 0.01) and IL-8 (P < 0.01) showing a potent anti-inflammatory activity. Silybin exerts its effects by directly inhibiting the ERK, MEK and Raf phosphorylation, reducing the activation of NHE1 (Na+/H+ exchanger, P < 0.05) and the IkB¦Á phosphorylation. In addition, Silybin was confirmed to act as a potent anti-oxidant agent. Conclusion The results of the study provide molecular insights into the potential therapeutic action of Silybin in chronic liver disease. This action seems to be mostly related to a marked inhibition of the production of pro-inflammatory cytokines, a clear anti-oxidant effect and a reduction of the direct and indirect pro-fibrogenic potential of HSC. Keywords: Silybin; Hepatic inflammation; Fibrogenesis Abbreviations: CLD, chronic liver disease; DMNQ, 2,3-dimethoxy-1- naphthoquinone; ECM, extracellular matrix; HSC, hepatic stellate cells; H2O2, hydrogen peroxide; IL, interleukin; [Ca2+]i, intracellular free calcium concentration; [3H]TdR, methyl-[3H] thymidine; MCP-1, monocyte chemoattractant protein-1; PDGF, platelet- derived growth factor; SFIF, serum-free/insulin-free; TGF-¦Â-1, transforming growth factor-¦Â1; X/XO, xanthine/xanthine oxidase ---------------- Silybin, a new iron-chelating agent. J Inorg Biochem. 2001 Jun;85(2-3):123-9. Borsari M, Gabbi C, Ghelfi F, Grandi R, Saladini M, Severi S, Borella F. Dipartimento di Chimica, Universit¨¤ di Modena, Via Campi 183-41100 Modena, Italy. Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin-Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin-Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. PMID: 11410232 -------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk |
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