Nematicidal effect of plumbagin on Caenorhabditis elegans: a model for testing a nematicidal drug
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Phantip Chaweeborisuit
Abstract
Plumbagin, (5-hydroxy-2-methyl-1,4-naphthoquinone), a natural substance found in the roots of plant species in the genus Plumbago, has been used as a traditional medicine against many diseases. In this study, Caenorhabditis elegans was used as a model for testing the anthelmintic effect of plumbagin. The compound exhibited a nematicidal effect against all stages of C. elegans: L4 was least susceptible, while L1 was most susceptible to plumbagin with an LC50 of 220 and 156 μM, respectively. Plumbagin inhibited C. elegans development from L1 to adult stages with an IC50 of 235 μM, and body length was also reduced at concentrations of 25 and 50 μg/ml. Brood sizes decreased from 203±6 to 43±6 and 18±3 eggs per hatch in plumbagin-treated worms at 10, 25, 50 μg/ml, respectively. Furthermore, plumbagin was lethal to strains resistant to the nematicides levamisole, albendazole, and ivermectin, indicating that it possesses a strong and unique nematicidal action. Plumbagin decreased the number of mitochondria in hypodermal and intestinal cells and body wall muscles and damaged the ultrastructure of these tissues. Taken together, plumbagin may be a new drug against parasitic nematodes.
Acknowledgments:
This research project was supported by the Faculty of Science, Mahidol University. All C. elegans strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). We thank Dr. Scott F. Cummins, University of the Sunshine Coast, Queensland, Australia, for assistance in language improvement and editing.
References
1. Padhye S, Dandawate P, Yusufi M, Ahmad A, Sarkar FH. Perspectives on medicinal properties of plumbagin and its analogs. Med Res Rev 2012;32:1131–58.10.1002/med.20235Search in Google Scholar PubMed
2. Tan M, Liu Y, Luo X, Chen Z, Liang H. Antioxidant activities of plumbagin and its Cu (II) complex. Bioinorg Chem Appl 2011;2011:898726.10.1155/2011/898726Search in Google Scholar PubMed PubMed Central
3. Tilak JC, Adhikari S, Devasagayam TP. Antioxidant properties of Plumbago zeylanica, an Indian medicinal plant and its active ingredient, plumbagin. Redox Rep 2004;9:219–27.10.1179/135100004225005976Search in Google Scholar PubMed
4. de Paiva SR, Figueiredo MR, Aragão TV, Kaplan MA. Antimicrobial activity in vitro of plumbagin isolated from Plumbago species. Mem Inst Oswaldo Cruz 2003;98:959–61.10.1590/S0074-02762003000700017Search in Google Scholar PubMed
5. Atjanasuppat K1, Wongkham W, Meepowpan P, Kittakoop P, Sobhon P, Bartlett A, et al. In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand. J Ethnopharmacol 2009;123:475–82.10.1016/j.jep.2009.03.010Search in Google Scholar PubMed
6. Luo P, Wong YF, Ge L, Zhang ZF, Liu Y, Liu L, et al. Anti-inflammatory and analgesic effect of plumbagin through inhibition of nuclear factor-κB activation. J Pharmacol Exp Ther 2010;335:735–42.10.1124/jpet.110.170852Search in Google Scholar PubMed
7. Kuo PL, Hsu YL, Cho CY. Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells. Mol Cancer Ther 2006;5:3209–21.10.1158/1535-7163.MCT-06-0478Search in Google Scholar PubMed
8. Hafeez BB, Jamal MS, Fischer JW, Mustafa A, Verma AK. Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-κB signaling pathways. Int J Cancer 2012;131:2175–86.10.1002/ijc.27478Search in Google Scholar PubMed PubMed Central
9. Sinha S, Pal K, Elkhanany A, Dutta S, Cao Y, Mondal G, et al. Plumbagin inhibits tumorigenesis and angiogenesis of ovarian cancer cells in vivo. Int J Cancer 2013;1332:1201–12.10.1002/ijc.27724Search in Google Scholar PubMed PubMed Central
10. Aziz MH, Dreckschmidt NE, Verma AK. Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer. Cancer Res 2008;68:9024–32.10.1158/0008-5472.CAN-08-2494Search in Google Scholar PubMed PubMed Central
11. Fetterer RH, Fleming MW. Effects of plumbagin on development of the parasitic nematodes Haemonchus contortus and Ascaris suum. Comp Biochem Physiol C 1991;100:539–42.10.1016/0742-8413(91)90036-SSearch in Google Scholar PubMed
12. Rhoads ML, Fetterer RH. Extracellular matrix degradation by Haemonchus contortus. J Parasitol 1996;38:379–83.10.2307/3284072Search in Google Scholar
13. Sen R, Chatterjee M. Plant derived therapeutics for the treatment of leishmaniasis. Phytomedicine 2011;18:1056–69.10.1016/j.phymed.2011.03.004Search in Google Scholar PubMed
14. Sharma N, Shukla AK, Das M, Dubey VK. Evaluation of plumbagin and its derivative as potential modulators of redox thiol metabolism of Leishmania parasite. Parasitol Res 2012;110:341–8.10.1007/s00436-011-2498-xSearch in Google Scholar PubMed
15. Saowakon N, Kueakhai P, Changklungmoa N, Lorsuwannarat N, Sobhon P. In vitro effect of purified plumbagin of Plumbago indica against motility of Paramphistomum cervi. Planta Med 2011;133:179–86.10.1055/s-0031-1282425Search in Google Scholar
16. Lorsuwannarat N, Saowakon N, Ramasoota P, Wanichanon C, Sobhon P. The anthelmintic effect of plumbagin on Schistosoma mansoni. Exp Parasitol 2013;133:18–27.10.1016/j.exppara.2012.10.003Search in Google Scholar PubMed
17. Zhang SM, Coultas KA. Identification of plumbagin and sanguinarine as effective chemotherapeutic agents for treatment of schistosomiasis. Int J Parasitol Drugs Drug Resist 2013;3:28–34.10.1016/j.ijpddr.2012.12.001Search in Google Scholar PubMed PubMed Central
18. Lorsuwannarat N, Piedrafita D, Chantree P, Sansri V, Songkoomkrong S, Bantuchai S, et al. The in vitro anthelmintic effects of plumbagin on newly excysted and 4-weeks-old juvenile parasites of Fasciola gigantica. Exp Parasitol 2014;136:5–13.10.1016/j.exppara.2013.10.004Search in Google Scholar PubMed
19. Brenner S. The genetics of Caenorhabditis elegans. Genetics 1974;77:71–94.10.1093/genetics/77.1.71Search in Google Scholar PubMed PubMed Central
20. Holden-Dye L, Walker RJ. Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans. WormBook 2014;1–29.10.1895/wormbook.1.143.2Search in Google Scholar PubMed PubMed Central
21. Burns AR, Luciani GM, Musso G, Bagg R, Yeo M, Zhang Y, et al. Caenorhabditis elegans is a useful model for anthelmintic discovery. Nat Commun 2015;6:7485.10.1038/ncomms8485Search in Google Scholar PubMed PubMed Central
22. Fleming JT, Squire MD, Barnes TM, Tornoe C, Matsuda K, Ahnn J, et al. Caenorhabditis elegans levamisole resistance genes lev-1, unc-29, and unc-38 encode functional nicotinic acetylcholine receptor subunits. J Neurosci 1997;17:5843–57.10.1523/JNEUROSCI.17-15-05843.1997Search in Google Scholar PubMed PubMed Central
23. Driscoll M, Dean E, Reilly E, Bergholz E, Chalfie M. Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity. J Cell Biol 1989;109:2993–3003.10.1083/jcb.109.6.2993Search in Google Scholar PubMed PubMed Central
24. Dent JA, Smith MM, Vassilatis DK, Avery L. The genetics of ivermectin resistance in Caenorhabditis elegans. Proc Natl Acad Sci 2000;97:2674–79.10.1073/pnas.97.6.2674Search in Google Scholar PubMed PubMed Central
25. Lewis JA, Fleming JT. Basic culture methods. Methods Cell Biol 1995;48:3–29.10.1016/S0091-679X(08)61381-3Search in Google Scholar
26. Stiernagle T. Maintenance of C. elegans. WormBook 2006;1–11.10.1895/wormbook.1.101.1Search in Google Scholar PubMed PubMed Central
27. Bischof LJ, Huffman DL, Aroian RV. Assays for toxicity studies in C. elegans with Bt crystal proteins. Methods Mol Biol 2006;351:139–54.10.1385/1-59745-151-7:139Search in Google Scholar PubMed
28. Solis GM, Petrascheck M. Measuring Caenorhabditis elegans life span in 96 well microtiter plates. J Vis Exp 2011;49:2496.10.3791/2496Search in Google Scholar PubMed PubMed Central
29. Artal-Sanz M, Tavernarakis N. Prohibitin couples diapause signalling to mitochondrial metabolism during ageing in C. elegans. Nature 2009;461:793–7.10.1038/nature08466Search in Google Scholar PubMed
30. Darr D, Fridovich I. Adaptation to oxidative stress in young, but not in mature or old, Caenorhabditis elegans. Free Radic Biol Med 1995;18:195–201.10.1016/0891-5849(94)00118-4Search in Google Scholar PubMed
31. Bull K, Cook A, Hopper NA, Harder A, Holden-Dye L, Walker RJ. Effects of the novel anthelmintic emodepside on the locomotion, egg-laying behaviour and development of Caenorhabditis elegans. Int J Parasitol 2007;37:627–36.10.1016/j.ijpara.2006.10.013Search in Google Scholar PubMed
32. Sant’anna V, Vommaro RC, de Souza W. Caenorhabditis elegans as a model for the screening of anthelminthic compounds: ultrastructural study of the effects of albendazole. Exp Parasitol 2013;135:1–8.10.1016/j.exppara.2013.05.011Search in Google Scholar PubMed
33. Sumsakul W, Plengsuriyakarn T, Chaijaroenkul W, Viyanant V, Karbwang J, Na-Bangchang K. Antimalarial activity of plumbagin in vitro and in animal models. BMC Complement Altern Med 2014;14:15.10.1186/1472-6882-14-15Search in Google Scholar PubMed PubMed Central
34. Krungkrai J, Kanchanarithisak R, Krungkrai SR, Rochanakij S. Mitochondrial NADH dehydrogenase from Plasmodium falciparum and Plasmodium berghei. Exp Parasitol 2002;100:54–61.10.1006/expr.2001.4674Search in Google Scholar PubMed
©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Editorial
- ZNC opens a new chapter focussing on the emerging field of natural and natural-like compounds
- Research Articles
- Design, synthesis and evaluation of antitumor activity of new rotundic acid acylhydrazone derivatives
- Synthesis and in vitro anti-HIV-1 activity of a series of N-arylsulfonyl-3-propionylindoles
- Jaspiferin G, a new isomalabaricane-type triterpenoid from the sponge Jaspis stellifera
- The effect of coniine on presynaptic nicotinic receptors
- Nematicidal effect of plumbagin on Caenorhabditis elegans: a model for testing a nematicidal drug
- Synthesis and biological evaluation of novel pyrimidines derived from 6-aryl-5-cyano-2-thiouracil
- Phytochemical investigation of the bioactive extracts of the leaves of Ficus cyathistipula Warb.
- Chemical composition and biological activity of the essential oil from Thymus lanceolatus
- Ascidian bioresources: common and variant chemical compositions and exploitation strategy – examples of Halocynthia roretzi, Styela plicata, Ascidia sp. and Ciona intestinalis
- Structural and evolutionary relationships among RuBisCOs inferred from their large and small subunits
Articles in the same Issue
- Frontmatter
- Editorial
- ZNC opens a new chapter focussing on the emerging field of natural and natural-like compounds
- Research Articles
- Design, synthesis and evaluation of antitumor activity of new rotundic acid acylhydrazone derivatives
- Synthesis and in vitro anti-HIV-1 activity of a series of N-arylsulfonyl-3-propionylindoles
- Jaspiferin G, a new isomalabaricane-type triterpenoid from the sponge Jaspis stellifera
- The effect of coniine on presynaptic nicotinic receptors
- Nematicidal effect of plumbagin on Caenorhabditis elegans: a model for testing a nematicidal drug
- Synthesis and biological evaluation of novel pyrimidines derived from 6-aryl-5-cyano-2-thiouracil
- Phytochemical investigation of the bioactive extracts of the leaves of Ficus cyathistipula Warb.
- Chemical composition and biological activity of the essential oil from Thymus lanceolatus
- Ascidian bioresources: common and variant chemical compositions and exploitation strategy – examples of Halocynthia roretzi, Styela plicata, Ascidia sp. and Ciona intestinalis
- Structural and evolutionary relationships among RuBisCOs inferred from their large and small subunits
