Milk thistle dietary supplements that contain silymarin are widely marketed and used in the USA and other countries for liver enhancement and recovery. More recently, silymarin has also been identified as a possible antiviral for the treatment of hepatitis C virus (HCV) infection. To assess different brands of commercially sold silymarin, 45 products were collected from local stores and analyzed for their silymarin content, antioxidant activities, and antiviral activity against HCV. Antioxidant activity was measured as radical scavenging activity using DPPH and by estimating their antioxidant capacity as trolox equivalent. Anti-HCV activity was measured in an HCV genotype 1b replication inhibition assay. Samples were found to vary widely in their silymarin content, with some samples having none or very low concentrations while silymarin represented higher than 80% of other samples. Both antioxidant and anti-HCV activity correlated with the overall level of silymarin.
References
[1]
Radimer, K.; Bindewald, B.; Hughes, J.; Ervin, B.; Swanson, C.; Picciano, M.F. Dietary supplement use by US adults: Data from the National Health and Nutrition Examination Survey, 1999–2000. Am. J. Epidemiol.？2004, 160, 339–349, doi:10.1093/aje/kwh207.
[2]
Qato, D.; Alexander, C.; Conti, R.; Johnson, M.; Schumm, P.; Lindau, S. Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States. JAMA？2008, 300, 2867–2878, doi:10.1001/jama.2008.892.
[3]
World Health Organization. The World Medicines Situation 2011—Traditional Medicines: Global Situation, Issues and Challenges; World Health Organization, 2011.
[4]
Flora, K.; Hahn, M.; Rosen, H.; Benner, K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am. J. Gastroenterol.？1998, 93, 139–143, doi:10.1111/j.1572-0241.1998.00139.x.
[5]
Mayer, K.; Myers, P.; Lee, S. Silymarin treatment of viral hepatitis: A systematic review. J. Viral Hepat.？2005, 12, 559–567, doi:10.1111/j.1365-2893.2005.00636.x.
[6]
Wellington, K.; Jarvis, B. Silymarin: A review of its clinical properties in the management of hepatic disorders. BioDrugs？2001, 15, 465–489, doi:10.2165/00063030-200115070-00005.
[7]
Saller, R.; Meier, R.; Brignoli, R. The use of silymarin in the treatment of liver diseases. Drugs？2001, 61, 2035–2063, doi:10.2165/00003495-200161140-00003.
[8]
Roy, S.; Gagan, G.; Agarwal, R. Silibinin prevents ultraviolet B radiation-induced epidermal damages in JB6 cells and mouse skin in a p53-GADD45α-dependent manner. Carcinogenesis？2012, 33, 629–636, doi:10.1093/carcin/bgr299.
[9]
Chilampalli, S.; Zhang, X.; Fahmy, H.; Kaushik, R.; Zeman, D.; Hildreth, M.; Dwivedi, C. Chemopreventive effects of honokiol on UVB-induced skin. Anticancer Res.？2010, 30, 777–783. 20392996
[10]
Bárcena, R.; Moreno, A.; Rodríguez-Gandía, M.; Albillos, A.; Arocena, C.; Blesa, C.; García-Hoz, F.; Graus, J.; Nu？o, J.; López-Hervás, P.; et al. Safety and anti-HCV effect of prolonged intravenous silibinin in HCV-genotype 1 subjects in the immediate liver transplant period. J. Hepatol.？2012. in press.
[11]
Mari？o, Z.; Crespo, G.; D’Amato, M.; Brambilla, N.; Giacovelli, G.; Rovati, L.; Costa, J.; Navasa, M.; Forns, X. Intravenous silibinin monotherapy shows significant antiviral activity in HCV-infected patients in the peri-transplantation period. J. Hepatol.？2012. in press.
[12]
Biermer, M.; Schlosser, B.; Fül？p, B.; van B？mmel, F.; Brodzinski, A.; Heyne, R.; Keller, K.; Sarrazin, C.; Berg, T. High-dose silibinin rescue treatment for HCV-infected patients showing suboptimal virologic response to standard combination therapy. J. Viral Hepat.？2012, 19, 547–553, doi:10.1111/j.1365-2893.2011.01572.x.
[13]
Rutter, K.; Scherzer, T.; Beinhardt, S.; Kerschner, H.; St？ttermayer, A.; Hofer, H.; Popow-Kraupp, T.; Steindl-Munda, P.; Ferenci, P. Intravenous silibinin as “rescue treatment” for on-treatment non-responders to pegylated interferon/ribavirin combination therapy. Antivir. Ther.？2011, 16, 1327–1333, doi:10.3851/IMP1942.
[14]
Payer, B.; Reiberger, T.; Rutter, K.; Beinhardt, S.; Staettermayer, A.; Peck-Radosavljevic, M.; Ferenci, P. Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV-HCV coinfected patient. J. Clin. Virol.？2010, 49, 131–133, doi:10.1016/j.jcv.2010.07.006.
[15]
Neumann, U.; Biermer, M.; Eurich, D.; Neuhaus, P.; Berg, T. Successful prevention of hepatitis C virus (HCV) liver graft reinfection by silibinin mono-therapy. J. Hepatol.？2010, 52, 951–952, doi:10.1016/j.jhep.2010.02.002.
[16]
Ferenci, P.; Scherzer, T.; Kerschner, H.; Rutter, K.; Beinhardt, S.; Hofer, H.; Sch？niger-Hekele, M.; Holzmann, H.; Steindl-Munda, P. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology？2008, 135, 1561–1567, doi:10.1053/j.gastro.2008.07.072.
[17]
Wagoner, J.; Negash, A.; Kane, O.; Martinez, L.; Nahmias, Y.; Bourne, N.; Owen, D.; Grove, J.; Brimacombe, C.; McKeating, J.; et al. Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology？2010, 51, 1912–1921, doi:10.1002/hep.23587.
[18]
Sy-Cordero, A.; Graf, T.; Nakanishi, Y.; Wani, M.; Agarwal, R.; Kroll, D.; Oberlies, N. Large scale isolation of flavonolignans from Silybum marianum (milk thistle) extract affords new minor constituents and preliminary structure-activity relationships. Planta Med.？2010, 76, 644–647, doi:10.1055/s-0029-1240624.
[19]
Daniela, D.; Ga？ák, R.; Marhol, P.; Biedermann, D.; Purchartova？, K.; Fedrigo, M.; Riva, S.; K？en, V. Enzymatic kinetic resolution of silybin diastereoisomers. J. Nat. Prod.？2010, 73, 613–619, doi:10.1021/np900758d.
[20]
K？en, V.; Kubisch, J.; Sedmera, P.; Halada, P.; P？ikrylová, V.; Jegorov, A.; Cvak, L.; Gebhardt, R.; Ulrichová, J.; ？imánek, V. Glycosylation of silybin. J. Chem. Soc.？1997, 2467–2474, doi:10.1039/A703283H.
[21]
Liu, J.; Manheimer, E.; Tsutani, K.; Gluud, C. Medicinal herbs for hepatitis C virus infection: A Cochrane hepato-biliary systematic review of randomized trials. Am. J. Gastroenterol.？2003, 98, 538–544, doi:10.1111/j.1572-0241.2003.07298.x.
[22]
Hammouda, F.; Ismail, S.; Hassan, N.; Zaki, A.; Kamel, A.; Rimpler, H. Evaluation of the silymarin content in Silybum marianum (L.) Gaertn. Cultivated under different agricultural conditions. Phytother. Res.？1993, 7, 90–91, doi:10.1002/ptr.2650070122.
[23]
Simanek, V.; Kren, V.; Ulrichova, J.; Vicar, J.; Cvak, L. Silymarin: What is in the name...? An appeal for a change of editorial policy. Hepatology？2000, 32, 442–444, doi:10.1053/jhep.2000.9770.
[24]
Farghaly, T.; Abdel Hafez, N.; Ragab, E.; Awad, H.; Abdalla, M. Synthesis, anti-HCV, antioxidant and peroxynitrite inhibitory activity of fused benzosuberone derivatives. Eur. J. Med. Chem.？2010, 45, 492–500, doi:10.1016/j.ejmech.2009.10.033.
[25]
Blight, K.; Kolykhalov, A.; Rice, C. Efficient initiation of HCV RNA replication in cell culture. Science？2000, 290, 1972–1974, doi:10.1126/science.290.5498.1972.
[26]
Zhong, J.; Gastaminza, P.; Cheng, G.; Kapadia, S.; Kato, T.; Burton, D.R.; Wieland, S.; Uprichard, S.; Wakita, T.; Chisari, F. Robust hepatitis C virus infection in vitro. Proc. Natl. Acad. Sci. USA？2005, 102, 9294–9299, doi:10.1073/pnas.0503596102. 15939869
[27]
Anthony, K.; Saleh, M. Chemical profiling and antioxidant activity of commercial milk thistle food supplements. J. Chem. Pharm. Res.？2012, 4, 4440–4450.
[28]
Brand-Williams, W.; Cuvelier, M.; Berset, C. Use of free radical method to evaluate antioxidant activity. Lebensm. Wiss. Technol.？1995, 28, 25–30, doi:10.1016/S0023-6438(95)80008-5.
[29]
Choi, S.; Sainz, J.; Corcoran, P.; Uprichard, S.; Jeong, H. Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cells. Xenobiotica？2009, 39, 205–217, doi:10.1080/00498250802613620.
[30]
Yu, X.; Sainz, B.; Uprichard, S. Development of a cell-based hepatitis C virus infection fluorescent resonance energy transfer assay for high-throughput antiviral compound screening. Antimicrob. Agents Chemother.？2009, 53, 4311–4319, doi:10.1128/AAC.00495-09. 19620334
[31]
Yu, X.; Uprichard, S. Cell-based hepatitis C virus infection fluorescence resonance energy transfer (FRET) assay for antiviral compound screening. Curr. Protoc. Microbiol.？2010, 17, 17–25.
[32]
Statistics SPSS Software, version 20, IBM Corporation, New York, NY, USA, 2011.
[33]
Gutteridge, J. Free radicals in disease processes: A compilation of cause and consequence. Free Radic. Res. Commun.？1993, 19, 141–158, doi:10.3109/10715769309111598. 8244084
[34]
Rivas-Estilla, A.; Marrugo, O.; Trujillo-Murillo, K.; Pérez-Ibave, D.; Charles-Ni？o, C.; Pedroza-Roldan, C.; Ríos-Ibarra, C.; Ramírez-Valles, E.; Ortiz-López, R.; Islas-Carbajal, M.; et al. Cu/Zn superoxide dismutase (sod 1) induction is implicated in the antioxidative and antiviral activity of acetylsalicylic acid in HCV-expressing cells. Am. J. Physiol. Gastrointest.？2012, 22. in press.
[35]
Farawela, H.; Khorshied, M.; Shaheen, I.; Gouda, H.; Nasef, A.; Abulata, N.; Mahmoud, H.; Zawam, H.; Mousa, S. The association between hepatitis C virus infection, genetic polymorphisms of oxidative stress genes and B-cell non-Hodgkin’s lymphoma risk in Egypt infection. Infect. Genetics Evol.？2012, 12, 1189–1194, doi:10.1016/j.meegid.2012.04.007.
[36]
Agrawal, L.; Louboutina, J.; Reyes, B.; Bockstaele, E.; Strayer, D. HIV-1 Tat neurotoxicity: A model of acute and chronic exposure, and neuroprotection by gene delivery of antioxidant enzymes. Neurobiol. Dis.？2012, 45, 657–670, doi:10.1016/j.nbd.2011.10.005.
[37]
Dworkin, B.; Wormser, G.; Axelrod, F.; Pierre, N.; Schwarz, E.; Seaton, T. Dietary intake in patients with acquired immunodeficiency syndrome (AIDS), patients with AIDS-related complex, and serologically positive human immunodeficiency virus patients: Correlations with nutritional status. J. Parenter. Enter. Nutr.？1990, 14, 605–609, doi:10.1177/0148607190014006605.
[38]
Abrams, B.; Duncan, D.; Hertz-Picciotto, I. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. J. Acquir. Immune Defic. Syndr.？1993, 6, 949–958. 8100273
