Natural Compounds Exerting Anthelmintic and/or Host-Protecting Effects During Parasitic Infections

  • Gabriela HrckovaEmail author
  • Samuel Velebny
Part of the SpringerBriefs in Pharmaceutical Science & Drug Development book series (BRIEFSPSDD)


Helminth parasites are able to regulate the host’s defense mechanisms in order to prevent their expulsion or killing and these are characterized by chronic immunosuppression and reduced pathology. Hence, any combined therapy would take advantage of the synergistic action of a drug and a natural compound, which exert immunomodulatory as well as antiparasitic activities. To date, only a few natural compounds with defined molecular structure and well-described biological and medicinal activities have been investigated as having also an anthelmintic effect. In this chapter, after a brief introduction to key features of immunosuppression and host pathology, anthelmintic and immunomodulatory activities of artemisinins, genistein, curcumin, and tannins are described with some insight into selective toxicity to pathogens and cancer cells, but very low toxicity to the normal cells in the hosts. The host-protecting effect of a natural compound with antioxidant and antifibrotic activities in reducing the host pathology, thus, contributing to the elevated drug efficacy, is also highlighted in this chapter. The focus is on phenolic compounds paeoniflorin and silymarin, so far examined in flatworm infections, and the description of several molecular mechanisms underlying the above beneficial effects is provided. Regarding immunomodulatory activity of all phenolic compounds reviewed, the direction to selected subsets of immune cells toward the immunological balance depends on the type of disease.


Helminths Natural phenolic compounds Immunosuppression Pathology Anthelmintic activity Artemisinins Genistein Curcumin Tannins Paeoniflorin Silymarin 


  1. Aggarwal BB, Harikumar KB (2009) Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 41:40–59. doi: 10.1016/j.biocel.2008.06.010 PubMedCrossRefGoogle Scholar
  2. Agrawal DK, Mishra PK (2010) Curcumin anti cancer action. Med Res Rev 30:818. doi: 10.1002/med.20188 PubMedGoogle Scholar
  3. Allam G (2009) Immunomodulatory effects of curcumin treatment on murine schistosomiasis mansoni. Immunobiol 214:712–727. doi: 10.1016/j.imbio.2008.11.017 CrossRefGoogle Scholar
  4. Andersen QM, Markham KR (2006) Flavonoids: chemistry, biochemistry and applications. Taylor and Francis Group, Boca RatonGoogle Scholar
  5. Anthony RM, Rutizky LI, Urban JF, Stadecker MJ, Gause WC (2007) Protective immune mechanisms in helminth infection. Nat Rev Immunol 7:975–987. doi: 10.1038/nri2199 PubMedCrossRefGoogle Scholar
  6. Araujo CAC, Leon LL (2001) Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 96:723–728. doi: org/10.1590/S0074-02762001000500026 PubMedCrossRefGoogle Scholar
  7. Balint GA (2001) Artemisinin and its derivatives: an important new class of antimalarial agents. Pharmacol Ther 90:261–265. doi: org/10.1016/S0163-7258(01)00140-1 PubMedCrossRefGoogle Scholar
  8. Baroni GS, D’Ambrosio L, Farretti G, Casini A, Di Sario A, Salzano R, Ridolfi F, Saccomanno S, Jezequel AM, Benedetti A (1998) Fibrogenic effect of oxidative stress on rat hepatic stellate cells. Hepatology 27:720–726. doi: 10.1002/hep.510270313 Google Scholar
  9. Bilzer M, Roggel F, Gerbes AL (2006) Role of Kupffer cells in the host defense and liver disease. Liver Int 26:1175–1186. doi: 10.1111/j.1478-3231.2006.01342.x PubMedCrossRefGoogle Scholar
  10. Burke ML, Jones MK, Gobert GN, Li YS, Ellis MK, McManus DP (2009) Immunopathogenesis of human schistosomiasis. Parasit Immunol 31:163–176. doi: 10.1111/j.1365-3024.2009.01098.x CrossRefGoogle Scholar
  11. Calixto JB, Otuki MF, Santos AR (2003) Anti-inflammatory compounds of plant origin. Part I. Action on arachidonic acid pathway, nitric oxide and nuclear factor kappa B (NF-kappa B). Planta Med 69:973–983. doi: 10.1055/s-2003-45141 PubMedCrossRefGoogle Scholar
  12. Calixto JB, Campos MM, Otuki MF, Santos AR (2004) Anti-inflammatory compounds of plant origin. Part II. Modulation of pro-inflammatory cytokines, chemokines and adhesion molecules. Planta Med 70:93–103. doi: 10.1055/s-2004-815483 PubMedCrossRefGoogle Scholar
  13. Chon SK, Kim NS (2005) Evaluation of silymarin in the treatment on asymptomatic Gairdia infections in dogs. Parasitol Res 97:445–451. doi: 10.1007/s00436-005-1462-z PubMedCrossRefGoogle Scholar
  14. Chu D, Luo Q, Li C, Gao Y, Yu L, Wei W, Wu Q, Shen J (2007) Paeoniflorin inhibits TGF-β1-mediated collagen production by Schistosoma japonicum soluble egg antigen in vitro. Parasitology 134:1611–1621. doi: 10.1017/S0031182007002946 PubMedCrossRefGoogle Scholar
  15. Chu D, Du M, Hu X, Wu Q, Shen J (2011) Paeoniflorin attenuates schistosomiasis japonica-associated liver fibrosis through inhibiting alternative activation of macrophages. Parasitology 138:1259–1271. doi: 10.1017/S0031182011001065 PubMedCrossRefGoogle Scholar
  16. Das R, Roy A, Ganguly A, Datta N, Majumder HK (2008) Curcumin, a dietary polyphenol, emerges as a novel inhibitor of DNA topoisomerase I of kinetoplastid parasite Leishmania donovani. Biochem J. doi: 10.1042/BJ20081134 Google Scholar
  17. De Blesser PJ, Xu G, Romboust K, Rogiers V, Geerts A (1999) Glutathione levels discriminate between oxidative stress and transforming growth factor-β signalling in activated rat hepatic stellate cells. J Biol Chem 274:33881–33887. doi: 10.1074/jbc.274.48.33881 CrossRefGoogle Scholar
  18. Dixon JB (1997) Echinococcosis. Comp Immun Microbiol Infect Dis 20:87–94. PII: S0147-9571(96)00019-7Google Scholar
  19. Duchen MR (2000) Mitochondria and calcium: from cell signalling to cell death. J Physiol (Lond) 529:57–68. doi: 10.1111/j.1469-7793.2000.00057.x CrossRefGoogle Scholar
  20. Dvořak Z, Kosina P, Walterova D, Šimanek V, Bachleda P, Ulrichova J (2003) Primary cultures of human hepatocytes as a tool in toxicity studies: cell protection against model toxins by flavonolignans obtained from Silybum marianum. Toxicol Lett 137: 201–212. doi:PII: S0378-4274(02)00406-XGoogle Scholar
  21. Eckstein-Ludwig U, Webb RJ, van Goethem IDA, East JM, Lee AG, Kimura M, O’Neill PM, Bray PG, Ward SA, Krishna S (2003) Artemisinins target the SERCA of Plasmodium falciparum. Nature 424:957–961. doi: 10.1038/nature01813 PubMedCrossRefGoogle Scholar
  22. Efferth T, Dunstan H, Sauerbrey A, Miyachi H, Chitambar CR (2001) The anti-malarial artesunate is also active against cancer. Int J Oncol 18:767–773PubMedGoogle Scholar
  23. El-Lakkany NM, Hammam OA, El-Maadawy WH, Badawy AA, Ain-Shoka AA, Ebeid FA (2012) Anti-inflammatory/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis. Parasites & Vectors 5: doi: 10.1186/1756-3305-5-9
  24. El-Ridi R, Aboueldahab M, Tallima H, Salah M, Mahana N, Fawzi S, Mohamed SH, Fahmy OM (2010) In vitro and in vivo activities of arachidonic acid against Schistosoma mansoni and Schistosoma haematobium. Antimicrob Agents Chemother 54:3383–3389. doi: 10.1128/AAC.00173-10 PubMedCrossRefGoogle Scholar
  25. El-Shenawy NS, Soliman MF, Reyad SI (2008) The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice. Rev Inst Med Trop Sao Paulo 50:29–36. doi: org/10.1590/S0036-46652008000100007 PubMedGoogle Scholar
  26. Fallon PG, Fookes RE, Wharton GA (1996) Temporal differences in praziquantel- and oxamniquine-induced tegumental damage to adult Schistosoma mansoni: implication for drug-antibody synergy. Parasitology 112:47–58. doi: org/10.1017/S0031182000065069 PubMedCrossRefGoogle Scholar
  27. Fischer M, Regitz Ch, Kahl M, Werthebach M, Boll M, Wenzel U (2012) Phytoestrogens genistein and daidzein affect immunity in the nematode Caenorhabditis elegans via alterations of vitellogenin expression. Molec Nutr & Food Res 56:957–965. doi: 10.1002/mnfr.201200006 CrossRefGoogle Scholar
  28. Fraschini G, Demartini G, Esposti D (2002) Pharmacology of silymarin. Clin Drug Invest 22:51–65Google Scholar
  29. Freitas TC, Pearce EJ (2010) Growth factors and chemotactic factors from parasitic helminths: molecular evidence for roles in host-parasite interactions versus parasite development. Int J Parasitol 40:761–773. doi: 10.1016/j.ijpara.2010.02.013 PubMedCrossRefGoogle Scholar
  30. Fujiwara N, Kobayashi K (2005) Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 4:281–286Google Scholar
  31. Gao F, Wei D, Bian T, Xie P. Zou J, Mu H, Zhang B, Zhou X (2012) Genistein attenuated allergic airway inflammation by modulating the transcription factors T-bet, GATA-3 and STAT-6 in a murine model of asthma. Pharmacology 89: 229–236. doi: 10.1159/000337180 Google Scholar
  32. Gause WC, Urban Jr JF, Stadecker MJ (2003) The immune response to parasitic helminths: insights from murine models. Trends Immunol 24:269–277. doi: 10.1016/S1471-4906(03)00101-7 Google Scholar
  33. Gharagozloo M, Velardi E, Bruscoli S, Agostini M, Di Sante M, Donato V, Amirghofran Z, Riccardi C (2010) Silymarin suppress CD4+T cell activation and proliferation: Effects on NF-κB activity and IL-2 production. Pharmacol Res 61:405–409Google Scholar
  34. Golenser J, Waknine JH, Krugliak M, Hunt NH, Grau GE (2006) Current perspectives on the mechanism of action of artemisinins. (Review article). Int J Parasitol 36:1427–1441. doi: 10.1016/j.ijpara.2006.07.011 PubMedCrossRefGoogle Scholar
  35. Gottstein B, Hemphill A (2008) Echinococcus multilocularis: the parasite-host interplay. Exp Parasitol 119:447–452. doi: 10.1016/j.exppara.2008.03.002 PubMedCrossRefGoogle Scholar
  36. Guerret S, Vuitton DA, Liance M, Pater C, Carbillet JP (1998) Echinococcus multilocularis: relationship between susceptibility/resistance and liver fibrogenesis in experimental mice. Parasitol Res 84:657–667. doi: not foundGoogle Scholar
  37. Gurib-Fakim A (2006) Medicinal plants: traditions of yesterday and drugs of tomorrow. Mol Aspects Med 27:1–93. doi: 10.1016/j.mam.2005.07.008 PubMedCrossRefGoogle Scholar
  38. Haddad M, Sauvain M, Deharo E (2011) Curcuma as a parasiticidal agent: a review. Planta Med 77(672–678):21104602. doi: 10.1055/s-0030-1250549 Google Scholar
  39. Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E (2007) Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflam Article ID: 45673, 10 pp doi: 10.1155/2007/45673
  40. Hemaiswarya S, Kruthiventi AK, Boble M (2008) Synergism between natural products and antibiotics against infectious diseases. Phytomedicine 15:639–652. doi: 10.1016/j.phymed.2008.06.008 PubMedCrossRefGoogle Scholar
  41. Hewitson JP, Grainger JR, Maizels RM (2009) Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity. Mol Biochem Parasitol 167:1–11. doi: 10.1016/j.molbiopara.2009.04.008 PubMedCrossRefGoogle Scholar
  42. Houghton PJ, Howes MJ, Lee CC, Steventon G (2007) Uses and abuses of in vitro tests in ethnopharmacology: visualizing an elephant. J Ethnopharmacol 110:391–400. doi: 10.1016/j.jep.2007.01.032 Google Scholar
  43. Hrčkova G, Velebný S (2007) Antibody response in mice infected with Mesocestoides vogae (syn. Mesocestoides corti) tetrathyridia after treatment with praziquantel and liposomised glucan. Parasitol Res 100:1351–1359. doi: 10.1007/s00436-006-0434-2 PubMedCrossRefGoogle Scholar
  44. Hrčkova G, Velebný S (2010) Flavonoid silymarin potentiates anthelmintic effect of praziquantel via down-regulation of oxidative stress and fibrogenesis in the liver. In: Proceedings of the World Medical Conference, Malta, Sept 15–17 2010. WSEAS Press, Wisconsin, pp 250–257Google Scholar
  45. Hrčkova G, Velebný S G (2012) Current situation and new possibilities in pharmacology of parasitic infections. Proceedings of the World Medical Conference, Kos-Island, July 14–17 2012, Wisconsin, WSEAS Press, pp 106–112Google Scholar
  46. Kang JS, Park KH, Lee H, Park KH, Kim HM (2010) Artemisinin inhibits lipopolysaccharide-induced nitric oxide production by blocking IFN-β production and STAT-1 signaling in macrophages. J Immunol 184:142.2 doi: not foundGoogle Scholar
  47. Keiser J, Utzinger J (2007) Artemisinins and synthetic trioxolanes in the treatment of helminth infections. Curr Opin Infect Dis 20:605–612. doi: 10.1097/QCO.0b013e3282f19ec4 PubMedCrossRefGoogle Scholar
  48. Keiser J, N’Guessan NA, Adoubryn KD, Silué KD, Vounatsou P, Hatz CH, Utzinger J, N’Goran K (2010) Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial. Clin Inf Dis 50:1205–1215. doi: 10.1086/651682 CrossRefGoogle Scholar
  49. Kolodziej H, Kayser O, Kiderlen AF, Hideyuki ITO, Hatano T, Yoshida T, Foo LY (2001) Proanthocyanidins and related compounds: Antileishmanial activity and modulatory effects on nitric oxide and Tumor Necrosis factor-α-release in the murine macrophage-like cell line RAW 264.7. Biol Pharm Bull 24:1016–1021. doi: 10.1248/bpb.24.1016 PubMedCrossRefGoogle Scholar
  50. Krishna S, Bustamante L, Haynes RK, Staines HM (2008) Artemisinins: their growing importance in medicine (Review). Trends Pharmacol Sci 29:520–527. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  51. Kroll DJ, Shaw HS, Oberlies NH (2007) Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integr Cancer Ther 6:110–119. doi: 10.1177/1534735407301825 PubMedCrossRefGoogle Scholar
  52. Kuhn I, Kellenberger E, Said-Hassane F, Villa P, Rognan D, Lobstein A, Haiech J, Hibert M, Schuber F, Muller-Steffner H (2010) Identification by high-throughput screening of inhibitors of Schistosoma mansoni NAD+ catabolizing enzyme. Bioorg Medic Chem 18:7900–7910. doi: 10.1016/j.bmc.2010.09.041 CrossRefGoogle Scholar
  53. Kuo FH, Jan TR (2009) Silibinin attenuates antigen-specific IgE production through the modulation of Th1/Th2 balance in ovalbumin-sensitized BALB/c mice. Phytomedicine 16:271–276. doi: 10.1016/j.phymed.2008.07.006 PubMedCrossRefGoogle Scholar
  54. Lightowlers MW, Rickard MD (1988) Excretory–secretory products of helminth parasites: effects on host immune responses. Parasitology 96:S123–S166. doi: org/10.1017/S0031182000086017 PubMedCrossRefGoogle Scholar
  55. Liu R, Dong HF, Guo Y, Zhao QP, Jiang MS (2011) Efficacy of praziquantel and artemisinin derivatives for the treatment and prevention of human schistosomiasis: a systematic review and meta-analysis. Parasites & Vectors 4: Article ID 201. doi: 10.1186/1756-3305-4-201
  56. Magalhães LG, Machado CB, Morais ER, Moreira EB, Soares CS, da Silva SH, da Silva Filho AA, Rodrigues V (2009) In vitro schistosomicidal activity of curcumin against Schistosoma mansoni adult worms. Parasitol Res 104:1197–1201. doi: 10.1007/s00436-008-1311-y Google Scholar
  57. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78:2081–2087. doi: 10.1016/j.lfs.2005.12.007 PubMedCrossRefGoogle Scholar
  58. Maizels RM, Yazdanbakhsh M (2003) Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat Rev Immunol 3:733–744. doi: 10.1038/nri1183 PubMedCrossRefGoogle Scholar
  59. Makkar HPS, Francis G, Becker K (2007) Bioactivity of phytochernicals in some lesser-known plants and their effects and potential applications in livestock and aquaculture production systems. Animal 1:137–139. doi: 10.1017/S1751731107000298 CrossRefGoogle Scholar
  60. Mata-Santos HA, Lino FG, Rocha CC, Paiva CN, Castelo Branco MT, Pyrrho Ados S (2010) Silymarin treatment reduces granuloma and hepatic fibrosis in experimental schistosomiasis. Parasitol Res 107:1429–1434. doi: 10.1007/s00436-010-2014-8 Google Scholar
  61. Meschnik SR (2002) Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol 32:1655–1660. PII:S0020-7519(02)00194-7Google Scholar
  62. Mishra S, Karmodiya K, Surolia N, Surolia A (2008) Synthesis and exploration of novel curcumin analogues as anti-malarial agents. Bioorg Med Chem 16:2894–2902. doi: 10.1016/j.bmc.2007.12.054 PubMedCrossRefGoogle Scholar
  63. Mota MLR, Thomas G, Filho BJM (1985) Anti inflammatory actions of tannins isolated from the bark of Anacardium occidentale L. J Ethnoparmacol 13:289–300. doi: 10.1016/0378-8741(85)90074-1 CrossRefGoogle Scholar
  64. Nery PS, Nogueira FA, Martins ER, Duarte ER (2010) Effects of Anacardium humile leaf extracts on the development of gastrointestinal nematode larvae of sheep. Vet Parasitol 171:361–364.  doi:10.1016/j.vetpar.2010.03.043 Google Scholar
  65. Olliaro PL, Haynes RK, Meunier B, Yuthavong Y (2001) Possible modes of action of the artemisinin-type compounds. Trends Parasitol 17:122–126. PII:S1471-922(00)01838-XGoogle Scholar
  66. Perkins S, Verschoyle RD, Hill K, Parveen I, Threadgill MD, Sharma RA, Williams ML, Steward WP, Gescher AJ (2002) Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familiar adenomatous polyposis. Cancer Epidemiol Biomarkers Preven 11:535–540Google Scholar
  67. Polkowski K, Mazurek AP (2000) Biological properties of genistein. Review of in vitro and in vivo data. Acta Polon Pharmac—Drug Res 57:135–155Google Scholar
  68. Rabia I, Nagy F, Aly E, Mohamed A, EL-Assal F, El-Amir A (2010) Effect of treatment with antifibrotic drugs in combination with PZQ in immunized Schistosoma mansoni infected murine model. J Am Sci 6:208–216Google Scholar
  69. Ramasamy K, Agarwal R (2008) Multitargeted therapy of cancer by silymarin. Cancer Lett 269:352–362. doi: 10.1016/j.canlet.2008.03.053 PubMedCrossRefGoogle Scholar
  70. Reeves HL, Friedman SL (2002) Activation of hepatic stellate cells—a key issue in liver fibrosis. Front BioSci 7:D808–D826PubMedCrossRefGoogle Scholar
  71. Rice-Evans C (2004) Flavonoids and isoflavones : absorption, metabolism, and bioactivity (Serial Review) (Ed. Rice-Evans). In: Flavonoids and isoflavones (phytoestrogens): absorption, metabolism, and bioactivity. Free Radical Biol Med 36:827–828. doi: 10.1016/j.freeradbiomed.2003.12.012
  72. Rothenberg ME, Hogan SP (2006) The eosinophils. Anu Rev Immunol 24:147–174CrossRefGoogle Scholar
  73. Sattelle DB, Buckingham SD, Akamatsu M, Matsuda K, Pienaar I, Jones AK, Sattelle BM, Almond A, Blundell CD (2009) Comparative pharmacology and computational modelling yield insights into allosteric modulation of human α7 nicotinic acetylcholine receptors Biochem Pharmacol 78:836–843. doi: 10.1016/j.bcp.2009.06.020 Google Scholar
  74. Sen R, Ganguly S, Saha P, Chatterjee M (2010) Efficacy of artemisinin in experimental visceral leishmaniasis. Int J Antimicrob Agents 36:43–49. doi: 10.1016/j.ijantimicag.2010.03.008 PubMedCrossRefGoogle Scholar
  75. Shakir L, Hussain M, Javeed A, Ashraf M, Riaz A (2011) Artemisinins and immune system. (Review). Eur J Pharmacol 668:6–14. doi: 10.1016/j.ejphar.2011.06.044 PubMedCrossRefGoogle Scholar
  76. Sing KP, Gerard HC, Hudson AP, Boros DL (2004) Expression of matrix metalloproteinases and their inhibitors during the resorption of schistosome egg-induced fibrosis in praziquantel-treated mice. Immunology 111:343–352. doi: 10.1111/j.I365-2567.2004.01817.x CrossRefGoogle Scholar
  77. Sutherland IA, Lee DL (1993) Acetylcholinesterase in infective-stage larvae of Haemonchus contortus, Ostertagia circumcincta and Trichostrongylus colubriformis resistant and susceptible to benzimidazole anthelmintics. Parasitology 107:553–557. doi: 10.1017/S003118200006813X PubMedCrossRefGoogle Scholar
  78. Tandon V, Pal P, Roy B, Rao HSP, Reddy KS (1997) In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an indigenous plant in Shillong, India. Parasitol Res 83:492–498. doi: 10.1007/s004360050286 PubMedCrossRefGoogle Scholar
  79. Taylor CK, Levy RM, Elliott JC, Burnett BP (2009) The effect of genistein aglycone on cancer and cancer risk: a review of in vitro, preclinical and clinical studies. Nutr Rev 67:398–415. doi: 10.1111/j.1753-4887.2009.00213.x PubMedCrossRefGoogle Scholar
  80. van Riet E, Hartgers FC, Yazdanbakhsh M (2007) Chronic helminth infections induce immunomodulation: consequences and mechanisms. Immunobiology 212:475–490. doi: 10.1016/j.imbio.2007.03.009 PubMedCrossRefGoogle Scholar
  81. Vanoevelen J, Dode L, Van Baelen K, Fairclough RJ, Missiaen L, Raeymaekers L, Wuytack F (2005) The secretory pathway Ca2+/Mn2+-ATPase 2 is a Golgi localized pump with high affinity for Ca2+ ions. J Biol Chem 280:22800–22808. doi: 10.1074/jbc.M501026200 PubMedCrossRefGoogle Scholar
  82. Velebný S, Hrčkova G, Kogan G (2008) Impact of treatment with praziquantel, silymarin and/or b-glucan on pathophysiological markers of liver damage and fibrosis in mice infected with Mesocestoides vogae (Cestoda) tetrathyridia. J Helminthol 82:211–219. doi: 10.1017/S0022149X08960776 PubMedCrossRefGoogle Scholar
  83. Velebný S, Hrčkova G, Königová A (2010) Reduction of oxidative stress and liver injury following silymarin and praziquantel treatment in mice with Mesocestoides vogae (Cestoda) infection. Parasitol Int 59:524–531. doi: 10.1016/j.parint.2010.06.012 PubMedCrossRefGoogle Scholar
  84. Verdrengh M, Collins LV, Bergin P, Tarkowski A (2004) Phytoestrogen genistein as an anti-staphylococcal agent. Microbes Infect 6:86–92. doi: 10.1016/j.micinf.2003.10.005 PubMedCrossRefGoogle Scholar
  85. Wang J, Zhou H, Zheng J, Cheng J, Liu W, Ding G, Wang L, Luo P, Lu Y, Cao H, Yu S, Li B, Zhang L (2006) The antimalarial artemisinin synergizes with antibiotics to protect against lethal live Escherichia coli challenge by decreasing proinflammatory cytokine release. Antimicrob Agents Chemother 50:2420–2427. doi: 10.1128/AAC.01066-05 PubMedCrossRefGoogle Scholar
  86. Wang J, Zhang Q, Jin S, He D, Zhao S, Liu S (2008) Genistein modulate immune responses in collagen-induced rheumatoid arthritis model. Maturitas 59:405–412. doi: 10.1016/j.maturitas.2008.04.003 PubMedCrossRefGoogle Scholar
  87. WHO (1995) Guidelines for surveillance, prevention, and control of echinococcosis/hydatidosis, 2nd edn. World Health Organisation, GenevaGoogle Scholar
  88. Williams RJ, Spencer JPE, Rice-Evans K (2004) Flavonoids: antioxidants or signalling molecules? (Serial Review) (Ed. Rice-Evans) In: Flavonoids and isoflavones (phytoestrogens): absorption, metabolism, and bioactivity. Free Radical Biol Med 36: 838–849. doi: 10.1016/j.freeradbiomed.2004.01.001
  89. Wojtkowiak A, Boczoń K, Wandurska-Nowak E (2007a) Effect in vitro of albendazole on the kinetics of cytosolic glutathione transferase from the rat liver. Wiad Parazytol 53:97–102PubMedGoogle Scholar
  90. Wojtkowiak A, Boczoń K, Wandurska-Nowak E, Derda M (2007b) Evaluation of effects of albendazole on the kinetics of cytosolic glutathione transferase in skeletal muscles during experimental trichinellosis in mice. Parasitol Res 100:647–651. doi: 10.1007/s00436-006-0285-x PubMedCrossRefGoogle Scholar
  91. World Health Organization (2005) Strategic orientation paper on prevention and control of malaria, roll back malaria department. Available at. Accessed May 11 2006
  92. Zhao M, Xue DB, Zheng B, Zhang WH, Pan SH, Sun B (2007) Induction of apoptosis by artemisinin revealing the severity of inflammation in caerulein-induced acute pancreatitis. World J Gastroenterol 13:5612–5617Google Scholar
  93. Zheng D, Wang Y, Zhang D, Liu Z, Duan C, Jia L, Wang F, Liu Y, Liu G, Hao L, Zhang Q (2011) In vitr o antitumor activity of silybin nanosuspension in PC-3 cells. Cancer Lett 307:158–164. doi: 10.1016/j.canlet.2011.03.028 PubMedCrossRefGoogle Scholar
  94. Zhong X, Zhu Y, Lu Q, Zhang J, Ge Z, Zheng S (2006) Silymarin causes caspase activation and apoptosis in K562 leukemia cells through inactivation of Akt pathway. Toxicology 29:211–216. doi: 10.1016/j.tox.2006.07.021 CrossRefGoogle Scholar

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© The Author(s) 2013

Authors and Affiliations

  1. 1.Slovak Academy of SciencesInsitute of ParasitologyKosiceSlovakia

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