1887

Abstract

In the absence of effective and safe treatment for visceral leishmaniasis or Kala-azar – a devastating parasitic disease caused by – the search for anti-leishmanial agents from natural resources in common use is imperative. Recently, the comparative anti-leishmanial activity of methanolic extracts from two landraces of landrace Bangla Mahoba (PB-BM) and landrace Kapoori Vellaikodi (PB-KV) – has been reported. Here, the putative pathway responsible for death induced by the effective extract of PB-BM methanolic extract in promastigotes, as well as the intracellular amastigote form of , was assessed using various biochemical approaches. It was found that PB-BM was capable of selectively inhibiting both stages of parasites by accelerating apoptotic events by generation of reactive oxygen species targeting the mitochondria without any cytotoxicity towards macrophages. The study was extended to determine the presence or absence of activity of the methanolic extract of PB-BM and PB-KV on the basis of differences in essential oil composition present in the extract assessed by GC and MS. The essential oil from PB-BM was found to be rich in eugenol compared with that from PB-KV. The anti-leishmanial efficacy of PB-BM methanolic extract mediated through apoptosis is probably due to the higher content of eugenol in the active landrace. This observation emphasizes the need to extend studies related to traditional medicines from bioactive plants below the species level to the gender/landrace level for better efficacy and reproducibility.

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2009-08-01
2019-10-18
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References

  1. Bortner, C. D., Oldenburg, N. B. & Cidlowski, J. A. ( 1995; ). The role of DNA fragmentation in apoptosis. Trends Cell Biol 5, 21–26.[CrossRef]
    [Google Scholar]
  2. Cao, G., Sofic, E. & Prior, R. L. ( 1997; ). Antioxidant and prooxidant behavior of flavonoids: structure–activity relationships. Free Radic Biol Med 22, 749–760.[CrossRef]
    [Google Scholar]
  3. Chang, K. P. ( 1980; ). Human cutaneous Leishmania in a mouse macrophage line: propagation and isolation of intracellular parasites. Science 209, 1240–1242.[CrossRef]
    [Google Scholar]
  4. Chipuk, J. E. & Green, D. R. ( 2005; ). Do inducers of apoptosis trigger caspase-independent cell death? Nat Rev Mol Cell Biol 6, 268–275.[CrossRef]
    [Google Scholar]
  5. Croft, S. L. ( 2001; ). Monitoring drug resistance in leishmaniasis. Trop Med Int Health 6, 899–905.[CrossRef]
    [Google Scholar]
  6. Das, M., Mukherjee, S. B. & Shaha, C. ( 2001; ). Hydrogen peroxide induces apoptosis-like death in Leishmania donovani promastigotes. J Cell Sci 114, 2461–2469.
    [Google Scholar]
  7. Debrabant, A., Lee, N., Bertholet, S., Duncan, R. & Nakhasi, H. L. ( 2003; ). Programmed cell death in trypanosomatids and other unicellular organisms. Int J Parasitol 33, 257–267.[CrossRef]
    [Google Scholar]
  8. Dey, R. & Moraes, C. T. ( 2000; ). Lack of oxidative phosphorylation and low mitochondrial membrane potential decrease susceptibility to apoptosis and do not modulate the protective effect of Bcl-xL in osteosarcoma cells. J Biol Chem 275, 7087–7094.[CrossRef]
    [Google Scholar]
  9. Duranteau, J., Chandel, N. S., Kulisz, A., Shao, Z. & Schumacker, P. T. ( 1998; ). Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem 273, 11619–11624.[CrossRef]
    [Google Scholar]
  10. Holzmuller, P., Sereno, D., Cavaleyra, M., Mangot, I., Daulouede, S., Vincendeau, P. & Lemesre, J. L. ( 2002; ). Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in Leishmania amazonensis amastigotes. Infect Immun 70, 3727–3735.[CrossRef]
    [Google Scholar]
  11. Iwu, M. M., Jackson, J. E. & Schuster, B. G. ( 1994; ). Medicinal plants in the fight against leishmaniasis. Parasitol Today 10, 65–68.[CrossRef]
    [Google Scholar]
  12. Kim, G. C., Choi, D. S., Lim, J. S., Jeong, H. C., Kim, I. R., Lee, M. H. & Park, B. S. ( 2006; ). Caspases-dependent apoptosis in human melanoma cell by eugenol. Korean J Anat 39, 245–253.
    [Google Scholar]
  13. Kumar, N., Gupta, S. & Tripathi, A. N. ( 2006; ). Gender-specific responses of Piper betle L. to low temperature stress: changes in chlorophyllase activity. Biol Plant 50, 705–708.[CrossRef]
    [Google Scholar]
  14. Mehta, A. & Shaha, C. ( 2004; ). Apoptotic death in Leishmania donovani promastigotes in response to respiratory chain inhibition: complex II inhibition results in increased pentamidine cytotoxicity. J Biol Chem 279, 11798–11813.[CrossRef]
    [Google Scholar]
  15. Padma, P. R., Lalitha, V. S., Amonkar, A. J. & Bhide, S. V. ( 1989; ). Anticarcinogenic effect of betel leaf extract against tobacco carcinogens. Cancer Lett 45, 195–202.[CrossRef]
    [Google Scholar]
  16. Paris, C., Loiseau, P. M., Bories, C. & Breard, J. ( 2004; ). Miltefosine induces apoptosis-like death in Leishmania donovani promastigotes. Antimicrob Agents Chemother 48, 852–859.[CrossRef]
    [Google Scholar]
  17. Ramji, N., Ramji, N., Iyer, R. & Chandrasekaran, S. ( 2002; ). Phenolic antibacterials from Piper betle in the prevention of halitosis. J Ethnopharmacol 83, 149–152.[CrossRef]
    [Google Scholar]
  18. Rao, A. R. ( 1984; ). Modifying influences of betel quid ingredients on B(a)P-induced carcinogenesis in the buccal pouch of hamster. Int J Cancer 33, 581–586.[CrossRef]
    [Google Scholar]
  19. Rocha, L. G., Almeida, J. R., Macedo, R. O. & Barbosa-Filho, J. M. ( 2005; ). A review of natural products with antileishmanial activity. Phytomedicine 12, 514–535.[CrossRef]
    [Google Scholar]
  20. Rybczynska, M., Spitaler, M., Knebel, N. G., Boeck, G., Grunicke, H. & Hofmann, J. ( 2001; ). Effects of miltefosine on various biochemical parameters in a panel of tumor cell lines with different sensitivities. Biochem Pharmacol 62, 765–772.[CrossRef]
    [Google Scholar]
  21. Sarkar, A., Sen, R., Saha, P., Ganguly, S., Mandal, G. & Chatterjee, M. ( 2008; ). An ethanolic extract of leaves of Piper betle (Paan) Linn mediates its antileishmanial activity via apoptosis. Parasitol Res 102, 1249–1255.[CrossRef]
    [Google Scholar]
  22. Singh, N. & Dube, A. ( 2004; ). Short report: fluorescent Leishmania: application to anti-leishmanial drug testing. Am J Trop Med Hyg 71, 400–402.
    [Google Scholar]
  23. Sudhandiran, G. & Shaha, C. ( 2003; ). Antimonial-induced increase in intracellular Ca2+ through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovani amastigotes. J Biol Chem 278, 25120–25132.[CrossRef]
    [Google Scholar]
  24. Suzuki, Y., Sugiyama, K. & Furuta, H. ( 1985; ). Eugenol-mediated superoxide generation and cytotoxicity in guinea pig neutrophils. Jpn J Pharmacol 39, 381–386.[CrossRef]
    [Google Scholar]
  25. Thakur, C. P., Kumar, M., Singh, S. K., Sharma, D., Prasad, U. S., Singh, R. S., Dhawan, P. S. & Achari, V. ( 1984; ). Comparison of regimens of treatment with sodium stibogluconate in kala-azar. Br Med J (Clin Res Ed) 288, 895–897.[CrossRef]
    [Google Scholar]
  26. Tripathi, S., Singh, N., Shakya, S., Dangi, A., Bhattacharya, S. M., Dube, A. & Kumar, N. ( 2006; ). Landrace/gender-based differences in phenol and thiocyanate contents and biological activity in Piper betle L. Curr Sci 91, 746–749.
    [Google Scholar]
  27. Ueda-Nakamura, T., Mendonça-Filho, R. R., Morgado-Díaz, J. A., Korehisa Maza, P., Prado Dias Filho, B., Aparício Garcia Cortez, D., Alviano, D. S., Rosa Mdo, S., Lopes, A. H. & other authors ( 2006; ). Antileishmanial activity of eugenol-rich essential oil from Ocimum gratissimum. Parasitol Int 55, 99–105.[CrossRef]
    [Google Scholar]
  28. Verma, A., Kumar, N. & Ranade, S. A. ( 2004; ). Genetic diversity amongst landraces of a dioecious vegetatively propagated plant, betelvine (Piper betle L.). J Biosci 29, 319–328.[CrossRef]
    [Google Scholar]
  29. Wright, S. E., Baron, D. A. & Heffner, J. E. ( 1995; ). Intravenous eugenol causes hemorrhagic lung edema in rats: proposed oxidant mechanisms. J Lab Clin Med 125, 257–264.
    [Google Scholar]
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