Skip to main content

Advertisement

SpringerLink
Log in

Immunomodulator Effect of Picroliv and its Potential in Treatment Against Resistant Plasmodium yoelii (MDR) Infection in Mice

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

The present study was envisaged to evaluate potential of combination therapy comprising of immunomodulator picroliv and antimalarial chloroquine against drug resistant Plasmodium yoelii (P. yoelii) infection in BALB/c mice.

Methods

The immunomodulatory potential of picroliv was established by immunizing animals with model antigen along with picroliv. Immune response was assessed using T-cell proliferation assay and also by determining the antibody isotype-profile induced in the immunized mice. In the next set of experiment, prophylactic potential of picroliv to strengthen antimalarial properties of chloroquine against P. yoelii (MDR) infection in BALB/c mice was assessed.

Results

T-cell proliferation as well as antibody production study reveals that picroliv helps in evoking strong immuno-potentiating response against model antigen in the immunized mice. Co-administration of picroliv enhances efficacy of CHQ against experimental murine malaria.

Conclusion

The activation of host immune system can increase the efficacy of chloroquine for suppression of drug resistant malaria infection in BALB/c mice.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6.
Fig. 7.

Similar content being viewed by others

Abbreviations

CHQ:

chloroquine

IFA:

incomplete Freunds adjuvant

μg:

microgram

MDR:

multi drug resistant

OVA:

ovalbumin

Pic:

picroliv

P. yoelii :

Plasmodium yoelii

References

  1. S. Gupta, S. C. Sharma, and V. M. L. Srivastav. Efficacy of Picroliv in combination with miltefosine, an orally effective antileishmanial drug against experimental visceral leishmaniasis. Acta Tropica. 94:41–47 (2005).

    Article  PubMed  CAS  Google Scholar 

  2. K. Arif, A. K. Aijaz, V. Dwivedi, M.G. Ahmad, S. Hakeem, and M. Owais. Coadministration of tuftsin augments antitumor efficacy of liposomised etoposide against fibrosarcoma in Swiss albino mice. Mol. Med. 13:5–6 (2007).

    Google Scholar 

  3. M. A. Khan, A. Khan, and M. Owais. Prophylactic use of liposomized tuftsin enhances the susceptibility of Candida albicans to fluconazole in leukopenic mice. FEMS Immunol. Med. Microbiol. 46(1):63–69 (2006).

    Article  PubMed  CAS  Google Scholar 

  4. M. A. Khan, and M. Owais. Immunomodulator tuftsin increases the susceptibility of Cryptococcus neoformans to liposomal amphotericin B in immunocompetent BALB/c mice. J Drug Target. 13(7):423–429 (2005).

    Article  PubMed  CAS  Google Scholar 

  5. A 5-minute briefing on the World Malaria Report 2005 from WHO and UNICEF. Available from http://rbm.who.int/wmr2005/pdf/adv_e.pdf.

  6. A. Bjorkman, and P. Phillips-Howard. The epidemiology of drug-resistant malaria. Trans R Soc Trop Med Hyg. 84:77–180 (1990).

    Google Scholar 

  7. R. Rastogi, S. Saksena, N. K. Garg, N. K. Kapoor, D. P. Agarwal, and B. N. Dhawan. Picroliv protects against alcohol-induced chronic hepatotoxicity in rats. Planta Med. 62(3):283–285 (1996).

    Article  PubMed  CAS  Google Scholar 

  8. Y. Dwivedi, R. Rastogi, N. K. Garg, and B. N. Dhawan. Picroliv and its components kutkuside and picroside I protect liver against galactosamine-induced damaged in rats. Pharmacol. Toxicol. 71:1–5 (1992).

    Article  Google Scholar 

  9. R. Chander, Y. Dwivedi, R. Rastogi, S. K. Sharma, N. K. Garg, N. K. Kapoor, and B. N. Dhawan. Evaluation of hepatoprotective activity of picroliv (from Picrorhiza kurroa) in Mastomys natalensis infected with Plasmodium berghei. Indian J. Med. Res. 92:34–37 (1990).

    PubMed  CAS  Google Scholar 

  10. A. Pui, R. P. Saxena, Sumati, P. Y. Guru, D. K. Kulshreshtha, K. C. Saxena, and B. N. Dhawan. Immunostimulant activity of Picroliv, the iridoid glycoside fraction of Picrorhiza kurroa, and its protective action against Leishmania donovani infection in hamsters. Planta Medica. 58:528–532 (1992).

    Article  Google Scholar 

  11. Y. Dwivedi, R. Rastogi, N. K. Garg, and B.N. Dhawan. Prevention of paracetamol-induced hepatic damage in rats by picroliv, the standardized active fraction from Picrorhiza kurroa. Phytotherapy Res. 5:115–119 (1991).

    Article  CAS  Google Scholar 

  12. J. N. Agrewala, M. Owais, C. M. Gupta, and G. C. Mishra. Antigen incorporation into liposomes results in the enhancement of IL-1, IL-4 and IgG1 secretion: evidence for preferential expansion of Th2 cells. Cytokines Mol. Therapy. 2:59–65 (1996).

    CAS  Google Scholar 

  13. J. N. Agrewala, S. Sumit, R. K. Verma, and G. C. Mishra. Differential effect of anti-B.7.1 and anti M 150 antibodies in restricting the delivery of co-stimulatory signals from B cells and macrophages. J. Immunol. 160:1067–1077 (1998).

    PubMed  CAS  Google Scholar 

  14. R. Chaturvedi, Y. Cheng, M. Asim, F. I. Bussière, H. Xu, A. P. Gobert, A. Hacker, R. A. Casero Jr, and K. T. Wilson. Induction of polyamine oxidase 1 by Helicobacter pylori causes macrophage apoptosis by hydrogen peroxide release and mitochondrial membrane depolarization. J. Biol. Chem. 279:40161–40173 (2004).

    Article  PubMed  CAS  Google Scholar 

  15. S. P. Nickell, G. A. Strykser, and C. Arevalo. Isolation from Trypanosoma crusi infected mice of CD8+ MHC-restricted cytotoxic T cells that lyse parasitic infected target cells. J. Immunol. 150:1446–1457 (1993).

    PubMed  CAS  Google Scholar 

  16. R. Agarwal, R. Tripathi, B. L. Tekwani, S. K. Jain, G. P. Dutta, and O. P. Shukla. Haem polymerase as a novel target of antimalarial action of cyproheptadine. Biochemical Pharmacology. 64:1399–1406 (2002).

    Article  Google Scholar 

  17. K. B. Kubata, N. Eguchi, Y. Urade, K. Yamashita, T. Mitamura, K. Tai, and T. Horii. Plasmodium falciparum produces prostaglandins that are pyrogenic, somnogenic and immunosuppressive substances in humans. J. Exp. Med. 188:1197–1202 (1998).

    Article  CAS  Google Scholar 

  18. E. M. Riley. Cellular and humoral response to Plasmodium falciparum antigen in Gambian children during and after an attack of acute Plasmodium falciparum malaria. Clin. Exp. Immunol. 73:17–22 (1988).

    PubMed  CAS  Google Scholar 

  19. J. M. Burns, D. D. Patricia, and D. M. Russo. Protective immunity against Plasmodium yoelii malaria induced by immunization with particulate blood antigens. Infect. Immun. 65:3138–3145 (1997).

    PubMed  CAS  Google Scholar 

  20. S. P. Pamela, S. C. Bosshardt, V. Uddhayukumar, L. Xiao, M. Kidd, R. L. Hunter et al. Prolonged expression of IFN-γ induced by protective blood-stage immunization against Plasmodium yoelii malaria. Vaccine. 18:173–180 (1999).

    Article  Google Scholar 

  21. S. Zhong, M. F. Tarn, D. Jankovic, and M. Stevenson. Vaccination with novel immunostimulatory adjuvants against blood stage antigens. Infect. Immun. 71:5178–5187 (2003).

    Article  CAS  Google Scholar 

  22. J. Langhorne, B. Simmon-Haahaus, and S. J. Mending. The role of CD4+ T-cells in the protective immune response to Plasmodium chabaudi in vivo. Immunol. Lett. 25:101–107 (1990).

    Article  PubMed  CAS  Google Scholar 

  23. R. L. Hunter, M. R. Kidd, M. R. Olsen, P. S. Patterson, and A. A. Lal. Induction of long lasting immunity to Plasmodium yoelii malaria with whole blood stage antigens and co-polymer adjuvants. J. Immunol. 154:1762–1769 (1995).

    PubMed  CAS  Google Scholar 

  24. J. Melancon-Kaplan, J. Burns Jr., A. Vaidya, H. K. Webster, and W. P. Weidanz. The immunology of malaria. In K. Warren (ed.), The immunology and molecular biology of parasitic disease, Alan R. Liss, New York, 1992, pp. 300–362.

    Google Scholar 

  25. J. Langhorne, S. J. Quin, and L. A. Sanni. Mouse models of blood stage malaria infections immune responses and cytokines involved in protection and pathology. In P. Perlmann, and M. Troye-Blomberg (eds.), Malaria Immunology, Karger, Basel Switzerland, 2002, pp. 204–228.

    Chapter  Google Scholar 

  26. N. T. Blomberg, W. P. Weidanz, and H. Heyde. The role of T-cells in immunity to malaria and pathogenesis of disease. In M. Wahlgren (ed.), Malaria molecular and clinical aspects, Harwood Acad, Netherlands, 1999, pp. 403–427.

    Google Scholar 

  27. K. Mohan, and M. M. Stevenson. Acquired immunity to asexual blood stages. In I. W. Sherman (ed.), Malaria: parasite biology, pathogenesis, and protection, American Soc. Microbiol, Washington, DC, 1998, pp. 467–493.

    Google Scholar 

  28. G. Suss, and J. R. Pink. A recombinant malaria protein that can induce Th-1 and CD8+ T-cell responses with out antibody formation. J. Immunol. 149:1334–1339 (1992).

    PubMed  CAS  Google Scholar 

  29. S. K. Sharma, S. Misra-Bhattacharya, F. Deba, P. Bajpai, A. Agrawal, and M. Owais. Escheriosome entrapped soluble blood stage antigens impart protective immunity against less susceptible isolate of Plasmodium yoelii nigeriensis in BALB/c mice. Vaccine. 14(7):948–956 (2006).

    Article  CAS  Google Scholar 

  30. D. Salmon, P. Deloron, C. Gaudin, K. Malhotra, J. Lebras, and J. Pocidalo. Activities of Pefloxacin and ciprofloxacin against experimental mice. Antimicrobial Agents and chemother. 34:2327–2330 (1990).

    CAS  Google Scholar 

  31. N. Mittal, N. Gupta, S. Saksena, N. Goyal, U. Roy, and A. K. Rastogi. Protective effect of picroliv from Picroohiza kurroa against Leishmania donovani infections in Mesocricetus auratus. Life. Sciences. 63:1823–1834 (1998).

    Article  PubMed  CAS  Google Scholar 

  32. R. T. Mehta, G. Lopez-Berestein, H. L. Roy, K. Mettta, R. A. White, and R. L. Juliano. Prophylaxis of murine candidiasis via application of liposome encapsulated amphoterecin B and a muramym di peptide analog, alone in combination. Antimicrob. Agents. Chemotherapy. 28:511–513 (1985).

    CAS  Google Scholar 

  33. A. O. Tziananabos, and R. L. Cisnevos. Prophylaxis with the immunomodulator PGG glycan enhances antibiotic efficacy in rats infected with antibiotic resistant bacteria. Ann N. Y. Acad. Sci. USA. 797:285–287 (1996).

    Article  Google Scholar 

Download references

Acknowledgements

The authors express their gratitude to Dr. C.M. Gupta, Director, CDRI, Lucknow for allowing us to avail of the institute’s research facilities.

Author information

Authors and Affiliations

  1. Department of Biochemistry, J. N. Medical College, Aligarh Muslim University, Aligarh, India

    Varun Dwivedi

  2. Inter-Disciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India

    Arif Khan, Nishat Fatima & Mohammad Owais

  3. Depto. de Biologia Geral, ICB/UFMG, Av. AntonioCarlos, Belo Horizonte, 6627, Brazil

    Azevedo Vasco

  4. Department of Parasitology, Central Drug Research Institute, Lucknow, India

    Vishal Kumar Soni, Anil Dangi & Shailja Misra-Bhattacharya

Authors
  1. Varun Dwivedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arif Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Azevedo Vasco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nishat Fatima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vishal Kumar Soni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anil Dangi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shailja Misra-Bhattacharya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad Owais
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohammad Owais.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dwivedi, V., Khan, A., Vasco, A. et al. Immunomodulator Effect of Picroliv and its Potential in Treatment Against Resistant Plasmodium yoelii (MDR) Infection in Mice. Pharm Res 25, 2312–2319 (2008). https://doi.org/10.1007/s11095-008-9631-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-008-9631-2

KEY WORDS

Search

Navigation