Skip to main content

Valeriana wallichii root extracts and fractions with activity against Leishmania spp

Abstract

Leishmanial diseases, posing a public health problem worldwide, are caused by Leishmania parasites with a dimorphic life cycle alternating between the promastigote and amastigote forms. Promastigotes transmitted by the vector are transformed into amastigotes residing in the host tissue macrophages. Presently, new antiparasitic agents are needed against Leishmania donovani and Leishmania major, the respective organisms causing visceral and cutaneous leishmaniasis, since the available treatments are unsatisfactory due to toxicity, high cost, and emerging drug resistance. Over the years, traditional medicinal flora throughout the world enriched the modern pharmacopeia. Hence, roots of ‘Indian Valerian’ (Valeriana wallichii DC) were studied for its antileishmanial activity for the first time. The methanol and chloroform extracts showed activity against L. donovani promastigotes and both promastigotes and amastigotes of L. major. The most active fraction, F3, obtained from the chloroform extract, showed IC50 at ∼3–7 μg/ml against both the promastigotes and 0.3 μg/ml against L. major amastigotes. On investigation of the mechanism of cytotoxicity in L. donovani promastigotes, the ‘hall-mark’ events of morphological degeneration, DNA fragmentation, externalization of phosphatidyl serine, and mitochondrial membrane depolarization indicated that F3 could induce apoptotic death in leishmanial cells. Therefore, the present study revealed a novel and unconventional property of V. wallichii root as a prospective source of effective antileishmanial agents.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Alvar J, Cañavate C, Gutiérrez-Solar B, Jiménez M, Laguna F, López-Vélez R, Molina R, Moreno J (1997) Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin Microbiol Rev 10:298–319

    PubMed  CAS  Google Scholar 

  2. Balderer G, Borbely A (1985) Effect of valerian on human sleep. Psychopharmacology 87:406–409

    PubMed  Article  CAS  Google Scholar 

  3. Barnes J, Anderson LA, Phillipson JD (2002) Herbal medicines. A guide for healthcare professionals, 2nd edn. Pharmaceutical, London, pp 468–476

    Google Scholar 

  4. Basu S, Hazra B (2006) Evaluation of nitric oxide scavenging activity, in vitro and ex vivo, of selected medicinal plants traditionally used in inflammatory diseases. Phytother Res 20:896–900

    PubMed  Article  Google Scholar 

  5. Cathcart R, Schwiers E, Ames BN (1983) Detection of picomole levels of hydrogen peroxide using a fluorescent dichlorofluorescein assay. Anal Biochem 134:111–116

    PubMed  Article  CAS  Google Scholar 

  6. Chan-Bacab MJ, Pena-Rodriguez LM (2001) Plant natural products with leishmanicidal activity. Nat Prod Rep 18:674–688

    PubMed  Article  CAS  Google Scholar 

  7. Harvey AL (1999) Medicines from nature: are natural products still relevant to drug discovery? Trends Pharmacol Sci 20:196–198

    PubMed  Article  CAS  Google Scholar 

  8. Hotez PJ, Pecoul B (2010) “Manifesto” for advancing the control and elimination of neglected tropical diseases. PLoS Negl Trop Dis 4:e718

    PubMed  Article  Google Scholar 

  9. Houghton PJ (1999) The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 51:505–512

    PubMed  Article  CAS  Google Scholar 

  10. Huber W, Koella JC (1993) A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites. Acta Trop 55:257–261

    PubMed  Article  CAS  Google Scholar 

  11. Jha TK (2006) Drug unresponsiveness & combination therapy for kala-azar. Indian J Med Res 123:389–398

    PubMed  CAS  Google Scholar 

  12. Kim J, Seo SM, Lee SG, Shin SC, Park IK (2008) Nematicidal activity of plants essential oils and components from coriander (Coriandrum sativum), Oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils against pinewood nematode Bursaphelenchus xylophilus. J Agric Food Chem 56:7316–7320

    PubMed  Article  CAS  Google Scholar 

  13. Lang T, Goyard S, Lebastard M, Milon G (2005) Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice. Cell Microbiol 7:383–392

    PubMed  Article  CAS  Google Scholar 

  14. Leathwood PD, Chauffard F (1985) Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med 2:144–148

    PubMed  Article  Google Scholar 

  15. Letchamo W, Ward W, Heard B, Heard D (2004) Essential oil of Valeriana officinalis L. cultivars and their antimicrobial activity as influenced by harvesting time under commercial organic cultivation. J Agric Food Chem 52:3915–3919

    PubMed  Article  CAS  Google Scholar 

  16. Lin S, Shen YH, Li HL, Yang XW, Chen T, Lu LH, Huang ZS, Liu RH, Xu XK, Zhang WD, Wang H (2009) Acylated iridoids with cytotoxicity from Valeriana jatamansi. J Nat Prod 72:650–655

    PubMed  Article  CAS  Google Scholar 

  17. Mathela CS, Chanotiya CS, Sammal SS, Pant AK, Pandey S (2005) Compositional diversity of terpenoids in the Himalayan Valeriana genera. Chem Biodivers 2:1174–1182

    PubMed  Article  CAS  Google Scholar 

  18. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    PubMed  Article  CAS  Google Scholar 

  19. Mukherjee P, Majee SB, Ghosh S, Hazra B (2009) Apoptosis-like death in Leishmania donovani promastigotes induced by diospyrin and its ethanolamine derivative. Int J Antimicrob Agents 34:596–601

    PubMed  Article  CAS  Google Scholar 

  20. Nadkarni KM (1976) Indian materia medica, 3rd edn. Popular Prakashan, Bombay, pp 1260–1262

    Google Scholar 

  21. Ponte-Sucre A, Vicik R, Schultheis M, Schirmeister T, Moll H (2006) Aziridine-2,3-dicarboxylates, peptidomimetic cysteine protease inhibitors with antileishmanial activity. Antimicrob Agents Chemother 50:2439–2447

    PubMed  Article  CAS  Google Scholar 

  22. Ponte-Sucre A, Faber JH, Gulder T, Kajahn I, Pedersen SE, Schultheis M, Bringmann G, Moll H (2007) Activities of naphthylisoquinoline alkaloids and synthetic analogs against Leishmania major. Antimicrob Agents Chemother 51:188–1894

    PubMed  Article  CAS  Google Scholar 

  23. Sánchez-Cañete MP, Carvalho L, Pérez-Victoria FJ, Gamarro F, Castanys S (2009) Low plasma membrane expression of the miltefosine transport complex renders Leishmania braziliensis refractory to the drug. Antimicrob Agents Chemother 53:1305–1313

    PubMed  Article  Google Scholar 

  24. Santin MR, dos Santos AO, Nakamura CV, Dias Filho BP, Ferreira IC, Ueda-Nakamura T (2009) In vitro activity of the essential oil of Cymbopogon citratus and its major component (citral) on Leishmania amazonensis. Parasitol Res 105(6):1489–1496

    PubMed  Article  Google Scholar 

  25. Santos DO, Coutinho CE, Madeira MF, Bottino CG, Vieira RT, Nascimento SB, Bernardino A, Bourguignon SC, Corte-Real S, Pinho RT, Rodrigues CR, Castro HC (2008) Leishmaniasis treatment—a challenge that remains: a review. Parasitol Res 103(1):1–10

    PubMed  Article  Google Scholar 

  26. Schleicher U, Bogdan C (2009) Generation, culture and flow-cytometric characterization of primary mouse macrophages. Methods Mol Biol 531:203–224

    PubMed  Article  CAS  Google Scholar 

  27. Sharma U, Velpandian T, Sharma P, Singh S (2009) Evaluation of anti-leishmanial activity of selected Indian plants known to have antimicrobial properties. Parasitol Res 105(5):1287–1293

    PubMed  Article  Google Scholar 

  28. Singh N, Ap G, Singh B, Kaul VK (2006) Quantification of valerenic acid in Valeriana jatamansi and Valeriana officinalis by HPTLC. Chromatographia 63:209–213

    Article  CAS  Google Scholar 

  29. WHO (2010) TDR news item. http://apps.who.int/tdr/svc/news-events/news/ntd-elimination

  30. Zhu BC-R, Henderson G, Yu Y, Laine RA (2003) Toxicity and repellency of patchouli oil and patchouli alcohol against Formosan subterranean termites Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae). J Agricult Food Chem 51:4585–4588

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. R. D. Singh, IHBT, Palampur, for authentication of plant sample. Prof. P. K. Sen, Bose Institute, and Dr. B. Mukherjee, Jadavpur University, Kolkata, are acknowledged for providing instrumental facility.

Funding

BH received financial support from Defense Research & Development Organisation (LSRB-166/ID/2008), Indian Council of Medical Research (3/1/3/WL/JRF/2008/MPD), and Department of Atomic Energy (2008/37/30/BRNS). Financial support by the Deutsche Forschungsgemeinschaft (SFB 630) given to UH and HM is gratefully acknowledged. BH and UH thank DST-DAAD for an exchange visit award.

Ethical standards

The authors declare that the experiments comply with the current laws of the country in which they were performed.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Ulrike Holzgrabe or Banasri Hazra.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ghosh, S., Debnath, S., Hazra, S. et al. Valeriana wallichii root extracts and fractions with activity against Leishmania spp. Parasitol Res 108, 861–871 (2011). https://doi.org/10.1007/s00436-010-2127-0

Download citation

Keywords

  • Leishmaniasis
  • Pentamidine
  • Cutaneous Leishmaniasis
  • Peritoneal Exudate Cell
  • Intracellular Reactive Oxygen Species Generation