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Piperine Enhances the Protective Effect of Curcumin Against 3-NP Induced Neurotoxicity: Possible Neurotransmitters Modulation Mechanism

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Abstract

3-Nitropropionic acid (3-NP) is a fungal toxin well established model used for inducing symptoms of Huntington’s disease. Curcumin a natural polyphenol has been reported to possess neuroprotective activity by decreasing oxidative stress. The aim of present study was to investigate neuroprotective effect of curcumin with piperine (bioavailability enhancer) against 3-NP induced neurotoxicity in rats. Administration of 3-NP (10 mg/kg for 21 days) showed loss in body weight, declined motor function and changes in biochemical (LPO, nitrite and glutathione level), neuroinflammatory (TNF-α and IL-1β level) and neurochemical (DA, NE, 5-HT, DOPAC, 5-HIAA and HVA). Chronic treatment with curcumin (25 and 50 mg/kg) and curcumin (25 mg/kg) with piperine (2.5 mg/kg) once daily for 21 days prior to 3-NP administration. All the behavioral parameters were studied at 1st, 7th, 14th, and 21st day. On 22nd day all the animals was scarified and striatum was separated. Curcumin alone and combination (25 mg/kg) with piperine (2.5 mg/kg) showed beneficial effect against 3-NP induced motor deficit, biochemical and neurochemical abnormalities in rats. Piperine (2.5 mg/kg) with curcumin (25 mg/kg) significantly enhances its protective effect as compared with curcumin alone treated group. The results of the present study indicate that protective effect of curcumin potentiated in the presence of piperine (bioavailability enhancer) against 3-NP–induced behavioral and molecular alteration.

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Abbreviations

3-NP:

3-Nitropropionic acid

HD:

Huntington’s disease

LPO:

Lipid peroxidation

IL:

Interlukin

ROS:

Reactive oxygen species

TNF-α:

Tumour necrosis factor-alpha

References

  1. Kumar P, Kalonia H, Kumar A (2010) Cyclosporine a attenuates 3-nitropropionic acid-induced Huntington-like symptoms in rats: possible nitric oxide mechanism. Int J Toxicol 29(3):318–325

    Article  CAS  PubMed  Google Scholar 

  2. Chakraborty J, Pandey M, Navneet A, Appukuttan T, Varghese M, Sreetama S et al (2014) Profilin-2 increased expression and its altered interaction with β-actin in the striatum of 3-nitropropionic acid-induced Huntington’s disease in rats. Neuroscience 281:216–228

    Article  CAS  Google Scholar 

  3. Chen JY, Wang EA, Cepeda C, Levine MS (2013) Dopamine imbalance in Huntington’s disease: a mechanism for the lack of behavioral flexibility. Front Neurosci 7:114

    PubMed Central  PubMed  Google Scholar 

  4. Khan A, Jamwal S, Bijjem K, Prakash A, Kumar P (2015) Neuroprotective effect of hemeoxygenase-1/glycogen synthase kinase-3β modulators in 3-nitropropionic acid-induced neurotoxicity in rats. Neuroscience 287:66–77

    Article  CAS  PubMed  Google Scholar 

  5. Colle D, Hartwig JM, Soares FAA, Farina M (2012) Probucol modulates oxidative stress and excitotoxicity in Huntington’s disease models in vitro. Brain Res Bull 87(4):397–405

    Article  CAS  PubMed  Google Scholar 

  6. Aggarwal BB, Deb L, Prasad S (2014) Curcumin differs from tetrahydrocurcumin for molecular targets. Signal Pathw Cell Responses Mol 20(1):185–205

    Google Scholar 

  7. Kumar P, Padi S et al (2007) Possible neuroprotective mechanisms of curcumin in attenuating 3-nitropropionic acid-induced neurotoxicity. Methods Find Exp Clin Pharmacol 29(1):19–26

    Article  CAS  PubMed  Google Scholar 

  8. Ghalandarlaki N, Alizadeh AM et al (2014) Nanotechnology-applied curcumin for different diseases therapy. Biomed Res Int 2014:1–23

    Article  Google Scholar 

  9. Sandhir R, Yadav A et al (2014) Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington’s disease. NeuroMol Med 16(1):106–118

    Article  CAS  Google Scholar 

  10. Patil UK, Singh A et al (2011) Role of piperine as a bioavailability enhancer. Int J Recent Adv Pharm Res 4:16–23

    Google Scholar 

  11. Thangarajan S, Deivasigamani A, Natarajan SS, Krishnan P, Mohanan SK (2014) Neuroprotective activity of L-theanine on 3-nitropropionic acid-induced neurotoxicity in rat striatum. Int J Neurosci 124(9):673–684

    Article  CAS  PubMed  Google Scholar 

  12. Plaa GL, Witschi H (1976) Chemicals, drugs, and lipid peroxidation. Annu Rev Pharmacol Toxicol 16(1):125–142

    Article  CAS  PubMed  Google Scholar 

  13. Daniel WL, Han MS, Lee J-S, Mirkin CA (2009) Colorimetric nitrite and nitrate detection with gold nanoparticle probes and kinetic end points. J Am Chem Soc 131(18):6362–6363

    Article  CAS  PubMed  Google Scholar 

  14. Koster J, Biemond P, Swaak A (1986) Intracellular and extracellular sulphydryl levels in rheumatoid arthritis. Ann Rheum Dis 45(1):44–46

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Lowry OH, Rosebrough NJ et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  16. Sharma S, Deshmukh R (2014) Vinpocetine attenuates MPTP-induced motor deficit and biochemical abnormalities in Wistar rats. Neuroscience 286:393–403

    Article  PubMed  Google Scholar 

  17. Kumar P, Kalonia H, Kumar A (2010) Cyclosporine a attenuates 3-nitropropionic acid-induced Huntington-like symptoms in rats: possible nitric oxide mechanism. Int J Toxicol 29(3):318–325

    Article  CAS  PubMed  Google Scholar 

  18. Kumar P, Kalonia H, Kumar A (2011) Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington’s-like symptoms: a comparative study. J Psychopharmacol 25(10):1399–1411

    Article  CAS  PubMed  Google Scholar 

  19. Kumar P, Kalonia H, Kumar A (2012) Possible GABAergic mechanism in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity. Eur J Pharmacol 674(2):265–274

    Article  CAS  PubMed  Google Scholar 

  20. Colle D, Santos DB, Moreira ELG, Hartwig JM, dos Santos AA, Zimmermann LT et al (2013) Probucol increases striatal glutathione peroxidase activity and protects against 3-nitropropionic acid-induced pro-oxidative damage in rats. PloS ONE 8(6):e67658

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Amor S, Puentes F, Baker D, Van Der Valk P (2010) Inflammation in neurodegenerative diseases. Immunology 129(2):154–169

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Im A-R, Chae S-W, jun Zhang G, Lee M-Y (2014) Neuroprotective effects of Psoralea corylifolia Linn seed extracts on mitochondrial dysfunction induced by 3-nitropropionic acid. BMC Complement Altern Med 14(1):370

    Article  PubMed Central  PubMed  Google Scholar 

  23. Túnez I, Tasset I, Pérez-De La Cruz V, Santamaría A (2010) 3-Nitropropionic acid as a tool to study the mechanisms involved in Huntington’s disease: past, present and future. Molecules 15(2):878–916

    Article  PubMed  Google Scholar 

  24. Hsieh H-L, Yang C-M (2013) Role of redox signaling in neuroinflammation and neurodegenerative diseases. Biomed Res Int 2013:1–18

    Google Scholar 

  25. Rossi S, Motta C, Studer V, Macchiarulo G, Volpe E, Barbieri F et al (2014) Interleukin-1β causes excitotoxic neurodegeneration and multiple sclerosis disease progression by activating the apoptotic protein p53. Mol Neurodegener 9(1):56

    Article  PubMed Central  PubMed  Google Scholar 

  26. Müller E, Parati E, Panerai A, Cocchi D, Caraceni T (1979) Growth hormone hyperresponsiveness to dopaminergic stimulation in Huntington’s chorea. Neuroendocrinology 28(5):313–319

    Article  PubMed  Google Scholar 

  27. Brouillet E, Jacquard C, Bizat N, Blum D (2005) 3-Nitropropionic acid: a mitochondrial toxin to uncover physiopathological mechanisms underlying striatal degeneration in Huntington’s disease. J Neurochem 95(6):1521–1540

    Article  CAS  PubMed  Google Scholar 

  28. Pant MK, Panthari P, Kharkwal A, Kharkwal H, Kharkwal H (2014). Curcumin: a wonder therapeutical drug. World J Pharm and Pharm Sci 3(6):374–396

    CAS  Google Scholar 

  29. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4(6):807–818

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors are thankful to Science and Engineering Board (SERB), Department of Science and Technology, Govt. of India, New Delhi for providing financial assistance under Fast Track Scheme (DST-SERB-FTYS) to Dr. Puneet Kumar.

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Singh, S., Jamwal, S. & Kumar, P. Piperine Enhances the Protective Effect of Curcumin Against 3-NP Induced Neurotoxicity: Possible Neurotransmitters Modulation Mechanism. Neurochem Res 40, 1758–1766 (2015). https://doi.org/10.1007/s11064-015-1658-2

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