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Inflammopharmacology

, Volume 26, Issue 4, pp 983–991 | Cite as

Plumbagin, a vitamin K3 analogue ameliorate malaria pathogenesis by inhibiting oxidative stress and inflammation

  • Amit Chand Gupta
  • Shilpa Mohanty
  • Archana Saxena
  • Anil Kumar Maurya
  • Dnyaneshwar U. Bawankule
Original Article
  • 108 Downloads

Abstract

Plumbagin, a vitamin K3 analogue is the major active constituent in several plants including root of Plumbago indica Linn. This compound has been shown to exhibit a wide spectrum of pharmacological activities. The present investigation was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria pathogenesis due to involvement of oxidative stress and inflammatory response in Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by intra-peritoneal injection of P. berghei infected red blood cells into the Swiss albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day following Peter’s 4 day suppression test. Oral administration of PL showed significant reduction of parasitaemia and increase in mean survival time. PL treatment is also attributed to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. Significant inhibition in level of oxidative stress and pro-inflammation related markers were observed in PL treated group. The trend of inhibition in oxidative stress markers level after oral treatment of PL was MPO > LPO > ROS in organ injury in P. berghei infected mice. This study showed that plumbagin is able to ameliorate malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism apart from its effect on reducing parasitaemia and increasing mean survival time of malaria-induced mice.

Graphical Abstract

Keywords

Plumbagin Malaria Oxidative stress Inflammation Mice 

Abbreviations

PL

Plumbagin

ROS

Reactive oxygen species

GSH

Glutathione peroxidase

SOD

Superoxide dismutase

TNF-α

Tumour necrosis factor-alpha

IL-6

Interleukin-6

IFN-γ

Interferon-gamma

IL-1β

Interleukin-1beta

CMC

Carboxymethyl cellulose

TBARS

Thiobarbituric acid reactive substances

MDA

Malondialdehyde

MPO

Myeloperoxidase

TMB

Tetramethylbenzidine

H2O2

Hydrogen peroxide

DCFH-DA

2′,7′-Dichlorofluorescein diacetate

DCF

Dichlorofluorescein

DMSO

Dimethylsulfoxide

FBS

Foetal bovine serum

LPS

Lipopolysaccharide

PBS

Phosphate-buffered saline

MTT

(3-(4,5-dimethylthiazol-2-yl)- 2,5-Diphenyltetrazolium)

Notes

Acknowledgements

The study was financially supported by the Council of Scientific and Industrial Research (CSIR), New Delhi under project BSC-0203 and HCP-0007. The authors are grateful to the UGC for providing fellowship to the first author and Director, CSIR-CIMAP, Lucknow, India for providing essential research facilities and support.

Compliance with ethical standards

Conflict of interest

Authors declare no conflicts of interest.

References

  1. Angulo I, Fresno M (2002) Cytokines in the pathogenesis of and protection against malaria. Clin Diagn Lab Immunol 9:1145–1152PubMedPubMedCentralGoogle Scholar
  2. Arruri V, Komirishetty P, Areti A, Dungavath SKN, Kumar A (2017) Nrf2 and NF-κB modulation by Plumbagin attenuates functional, behavioural and biochemical deficits in rat model of neuropathic pain. Pharmacol Rep 69:625–632CrossRefPubMedGoogle Scholar
  3. Ashley EA, Dhorda M, Fairhurst RM, Amaratunga C, Lim P, Suon S, Sreng S, Anderson JM, Mao S, Sam B (2014) Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371:411–423CrossRefPubMedPubMedCentralGoogle Scholar
  4. Del Maestro R, McDonald W (1985) Oxidative enzymes in tissue homogenates. CRC Handb Methods Oxyg Rad Res 1:294–296Google Scholar
  5. Draper H, Hadley M (1990) Malondialdehyde determination as index of lipid Peroxidation. Methods Enzymol 186:421–431CrossRefPubMedGoogle Scholar
  6. Driver AS, Kodavanti PRS, Mundy WR (2000) Age-related changes in reactive oxygen species production in rat brain homogenates. Neurotoxicol Teratol 22:175–181CrossRefPubMedGoogle Scholar
  7. Guha M, Kumar S, Choubey V, Maity P, Bandyopadhyay U (2006) Apoptosis in liver during malaria: role of oxidative stress and implication of mitochondrial pathway. FASEB J Off Publ Fed Am Soc Exp Biol 20:1224–1226Google Scholar
  8. Guiguemde WA, Hunt NH, Guo J, Marciano A, Haynes RK, Clark J, Guy RK, Golenser J (2014) Treatment of murine cerebral malaria by artemisone in combination with conventional antimalarial drugs: antiplasmodial effects and immune responses. Antimicrob Agents Chemother 58:4745–4754CrossRefPubMedPubMedCentralGoogle Scholar
  9. Guo YX, Liu L, Yan DZ, Guo JP (2017) Plumbagin prevents osteoarthritis in human chondrocytes through Nrf-2 activation. Mol Med Rep 15:2333–2338CrossRefPubMedGoogle Scholar
  10. Hazra B, Sarkar R, Bhattacharyya S, Ghosh PK, Chel G, Dinda B (2002) Synthesis of plumbagin derivatives and their inhibitory activities against Ehrlich ascites carcinoma in vivo and Leishmania donovani promastigotes in vitro. Phytother Res 16:133–137CrossRefPubMedGoogle Scholar
  11. Kalia S, Walter NS, Bagai U (2015) Antimalarial efficacy of Albizia lebbeck (Leguminosae) against Plasmodium falciparum in vitro & P. berghei in vivo. Indian J Med Res 142:S101CrossRefPubMedPubMedCentralGoogle Scholar
  12. Mohanty S, Maurya AK, Saxena A, Shanker K, Pal A, Bawankule DU (2015) Flavonoids rich fraction of Citrus limetta fruit peels reduces proinflammatory cytokine production and attenuates malaria pathogenesis. Curr Pharm Biotechnol 16:544–552CrossRefPubMedGoogle Scholar
  13. Pabon A, Carmona J, Burgos LC, Blair S (2003) Oxidative stress in patients with non-complicated malaria. Clin Biochem 36:71–78CrossRefPubMedGoogle Scholar
  14. Sandur SK, Ichikawa H, Sethi G, Ahn KS, Aggarwal BB (2006) Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agents. J Biol Chem 281:17023–17033CrossRefPubMedGoogle Scholar
  15. Saxena A, Yadav D, Mohanty S, Cheema HS, Gupta MM, Darokar MP, Bawankule DU (2016) Diarylheptanoids Rich Fraction of Alnus nepalensis attenuates malaria pathogenesis: in-vitro and In-vivo Study. Phytother Res 30:940–948CrossRefPubMedGoogle Scholar
  16. Schmidt H, Grune T, Muller R, Siems WG, Wauer RR (1996) Increased levels of lipid peroxidation products malondialdehyde and 4-hydroxynonenal after perinatal hypoxia. Pediatr Res 40:15–20CrossRefPubMedGoogle Scholar
  17. Schofield L, Grau GE (2005) Immunological processes in malaria pathogenesis. Nat Rev Immunol 5:722–735CrossRefPubMedGoogle Scholar
  18. Sharma S, Chattopadhyay SK, Yadav DK, Khan F, Mohanty S, Maurya A, Bawankule DU (2012) QSAR, docking and in vitro studies for anti-inflammatory activity of cleomiscosin A methyl ether derivatives. Eur J Pharm Sci 47:952–964CrossRefPubMedGoogle Scholar
  19. Sukkasem N, Chatuphonprasert W, Tatiya-aphiradee N, Jarukamjorn K (2016) Imbalance of the antioxidative system by plumbagin and Plumbago indica L. extract induces hepatotoxicity in mice. J Intercult Ethnopharmacol 5:137CrossRefPubMedPubMedCentralGoogle Scholar
  20. Sumsakul W, Plengsuriyakarn T, Chaijaroenkul W, Viyanant V, Karbwang J, Na-Bangchang K (2014) Antimalarial activity of plumbagin in vitro and in animal models. BMC Compl Altern Med 14:1–6CrossRefGoogle Scholar
  21. Suzuki KT, Tanaka Y, Kawamura R (1983) Properties of metallothionein induced by zinc, copper and cadmium in the frog, Xenopus laevis. Comparative biochemistry and physiology. C, Comp Pharmacol Toxicol 75:33–37Google Scholar
  22. Wells TN (2011) Natural products as starting points for future anti-malarial therapies: going back to our roots? Malar J 10:S3CrossRefPubMedPubMedCentralGoogle Scholar
  23. WHO (2015) Guidelines for the treatment of malaria-3rd edition. World Health Organization, Geneva, Switzerland. ISBN: 978-92-4154912-7Google Scholar
  24. Yu JH, Kim H (2014) Oxidative stress and inflammatory signaling in cerulein pancreatitis. World J Gastroenterolo WJG 20:17324CrossRefGoogle Scholar
  25. Zhang W, Cheng L, Hou Y, Si M, Zhao YP, Nie L (2015) Plumbagin protects against spinal cord injury-induced oxidative stress and inflammation in wistar rats through Nrf-2 upregulation. Drug Res 65:495–499Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Amit Chand Gupta
    • 1
  • Shilpa Mohanty
    • 1
  • Archana Saxena
    • 1
  • Anil Kumar Maurya
    • 1
  • Dnyaneshwar U. Bawankule
    • 1
  1. 1.In-Vivo Testing Laboratory, Molecular Bioprospection DepartmentCSIR-Central Institute of Medicinal and Aromatic PlantsLucknowIndia

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