Skip to main content

Advertisement

Log in

An ethanolic extract of leaves of Piper betle (Paan) Linn mediates its antileishmanial activity via apoptosis

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

An unprecedented increase in the incidence of unresponsiveness to antimonial compounds has highlighted the urgent need to develop new antileishmanial agents. The leaves of Piper betle (locally known as Paan) have long been in use in the Indian indigenous system of medicine for its antimicrobial properties but its antileishmanial potential has not been studied. Accordingly, an ethanolic extract of leaves of Piper betle (PB) was tested for its antileishmanial activity that was evidenced in both promastigotes and amastigotes, with IC50 values of 9.8 and 5.45 μg/ml, respectively; importantly, it was accompanied by a safety index of >12-fold. This leishmanicidal activity of PB was mediated via apoptosis as evidenced by morphological changes, loss of mitochondrial membrane potential, in situ labeling of DNA fragments by terminal deoxyribonucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling, and cell-cycle arrest at the sub-G0/G1 phase. Taken together, the data indicate that PB has promising antileishmanial activity that is mediated via programmed cell death and, accordingly, merits consideration and further investigation as a therapeutic option for the treatment of leishmaniasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ahua KM, Ioset JR, Ioset KN, Diallo D, Mauel J, Hostettmann K (2007) Antileishmanial activities associated with plants used in the Malian traditional medicine. J Ethnopharmacol 110:99–104

    Article  PubMed  Google Scholar 

  • Arnoult D, Akarid K, Grodet A, Petit PX, Estaquier J, Amiesen JC (2002) On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine protease activation and mitochondrion permeabilization. Cell Death Differ 9:65–81

    Article  PubMed  CAS  Google Scholar 

  • Croft SL, Sundar S, Fairlamb AH (2006) Drug resistance in leishmaniasis. Clin Microbiol Rev 19:111–126

    Article  PubMed  CAS  Google Scholar 

  • CSIR (1969) The wealth of India, vol. 8. Council of Scientific and Industrial Research, New Delhi, pp 84–94

    Google Scholar 

  • Desjeux P (2004) Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27:305–318

    Article  PubMed  CAS  Google Scholar 

  • Dube A, Singh S, Sundar S, Singh N (2005) Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models. Parasitol Res 96:216–223

    Article  PubMed  Google Scholar 

  • Dutta A, Mandal G, Mandal C, Chatterjee M (2007a) In vitro antileishmanial activity of Aloe vera leaf exudate: a potential herbal therapy in leishmaniasis. Glycoconj J 24:81–86

    Article  PubMed  CAS  Google Scholar 

  • Dutta A, Bandyopadhyay S, Mandal C, Chatterjee M (2007b) Aloe vera leaf exudate induces a caspase independent cell death in Leishmania donovani promastigotes. J Med Microbiol 56:629–636

    Article  PubMed  CAS  Google Scholar 

  • Evans PH, Bower WS, Funk EJ (1984) Identification of fungicidal and nematocidal components in the leaves of Piper betle (Piperaceae). J Agric Food Chem 32:1254–1256

    Article  CAS  Google Scholar 

  • Ganguly S, Bandyopadhyay S, Sarkar A, Chatterjee M (2006) Development of a semi automated colorimetric assay for screening anti-leishmanial agents. J Microbiol Methods 66:79–86

    Article  PubMed  CAS  Google Scholar 

  • Ganguly S, Mula S, Chattopadhyay S, Chatterjee M (2007) An ethanol extract of Piper betle Linn. mediates its anti-inflammatory activity via down-regulation of nitric oxide. J Pharm Pharmacol 59:711–718

    Article  PubMed  CAS  Google Scholar 

  • Mittra B, Saha A, Chowdhury AR, Pal C, Mandal S, Mukhopadhyay S, Bandyopadhyay S, Majumder HK (2000) Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis. Mol Med 6:527–541

    Article  PubMed  CAS  Google Scholar 

  • Moreira ME, Del Portillo HA, Milder RV, Balanco JM, Barcinski MA (1996) Heat shock induction of apoptosis in promastigotes of the unicellular organism Leishmania (Leishmania) amazonensis. J Cell Physiol 167:305–313

    Article  PubMed  CAS  Google Scholar 

  • Nalina T, Rahim JHA (2007) The crude aqueous extract of Piper betle L. and its antibacterial effect towards Streptococcus mutans. Am J Biotech Biochem 3:10–15

    Article  Google Scholar 

  • Sawangjaroen N, Phongpaichit S, Subhadhirasakul S, Visutthi M, Srisuwan N, Thammapalerd N (2006) The anti-amoebic activity of some medicinal plants used by AIDS patients in southern Thailand. Parasitol Res 98:588–592

    Article  PubMed  Google Scholar 

  • Sen N, Das BB, Ganguly A, Mukherjee T, Tripathi G, Bandyopadhyay S, Rakshit S, Sen T, Majumder HK (2004) Camptothecin induced mitochondrial dysfunction leading to programmed cell death in unicellular hemoflagellate Leishmania donovani. Cell Death Differ 11:924–936

    Article  PubMed  CAS  Google Scholar 

  • Sen R, Bauri A, Chattopadhyay S, Chatterjee M (2007a) Antipromastigote activity of the malabaricones of Myristica malabarica (rampatri). Phytother Res 21:592–595

    Article  PubMed  CAS  Google Scholar 

  • Sen R, Bandyopadhyay S, Dutta A, Mandal G, Ganguly S, Saha P, Chatterjee M (2007b) Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes. J Med Microbiol 56:1213–1218

    Article  PubMed  CAS  Google Scholar 

  • Singh N, Mishra PK, Kapil A, Arya KR, Maurya R, Dube A (2005) Efficacy of Desmodium gangeticum extract and its fractions against experimental visceral leishmaniasis. J Ethnopharmacol 98:83–88

    Article  PubMed  Google Scholar 

  • Sundar S, Chatterjee M (2006) Visceral leishmaniasis - current therapeutic modalities. Indian J Med Res 123:345–352

    PubMed  CAS  Google Scholar 

  • Sundar S, More DK, Singh MK, Singh VP, Sharma S, Makharia A, Kumar PC, Murray HW (2000) Failure of pentavalent antimony in visceral leishmaniasis in India: report from the center of the Indian epidemic. Clin Infect Dis 31:1104–1107

    Article  PubMed  CAS  Google Scholar 

  • Tasdemir D, Kaiser M, Brun R, Yardley V, Schmidt TJ, Tosun F, Ruedi P (2006) Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimicrob Agents Chemother 50:1352–1364

    Article  PubMed  CAS  Google Scholar 

  • Trakranrungsie N, Chatchawanchonteera A, Khunkitti W (2007) Ethnoveterinary study for antidermatophytic activity of Piper betle, Alpinia galanga and Allium ascalonicum extracts in vitro. Res Vet Sci 84(1):80–84

    Article  PubMed  Google Scholar 

  • Verma NK, Singh G, Dey CS (2007) Miltefosine induces apoptosis in arsenite-resistant Leishmania donovani promastigotes through mitochondrial dysfunction. Exp Parasitol 116:1–13

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work received financial assistance from the Life Sciences Research Board, Defense Research Development Organization, the University Grants Commission, Council of Scientific and Industrial Research, Government of India. RS, SG, and GM are recipients of Senior Research fellowships from Lavanya Prova Bose Trust, University Grants Commission and Council of Scientific and Industrial Research, Government of India, respectively.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mitali Chatterjee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sarkar, A., Sen, R., Saha, P. et al. An ethanolic extract of leaves of Piper betle (Paan) Linn mediates its antileishmanial activity via apoptosis. Parasitol Res 102, 1249–1255 (2008). https://doi.org/10.1007/s00436-008-0902-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-008-0902-y

Keywords

Navigation