Skip to main content

Advertisement

Log in

Neuroprotective efficacy of Nardostachys jatamansi and crocetin in conjunction with selenium in cognitive impairment

  • Original Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Oxidative stress leads to complex biochemical alterations, and has been implicated in the progressive loss of learning and memory. Supplementing and boosting the endogenous antioxidant defense system could impede the progression of various types of neurodegeneration. In the present study, we have investigated the neuroprotective efficacy of a low-dose combination of certain promising and powerful natural antioxidants in an experimental model of cognitive impairment. Combined pretreatment with the extract of Nardosatchys jatamansi (N), crocetin (C) and selenium (Se) as sodium selenite (N, 200 mg/kg + C, 25 μg/kg + Se, 0.05 mg/kg body weight) for 15 days led to improved behavioral outcomes in streptozotocin (STZ)-induced cognitive impairment in rats. While intracerebroventricular (ICV) infusion of STZ resulted in the significant elevation of markers of oxidative stress and depletion of endogenous antioxidant defense system in the vehicle-pretreated group, these markers of oxidative stress and antioxidant enzymatic as well as non-enzymatic defense lines were attenuated in the group pretreated with the combination of antioxidants (NCSe). NCSe pretreatment markedly improved the performance of animals in passive avoidance test and Morris water maze (MWM) tasks, significantly reduced the level of TBARS, and elevated the content of glutathione and activities of antioxidant enzymes (glutathione peroxidase, glutathione-S-transferase and catalase). Our study reflects the synergistic potential of the above combination and concludes that a multimodal approach could be beneficial rather than a singular intervention.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623

    Article  PubMed  CAS  Google Scholar 

  2. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate and neurodegenerative disorders. Science 262:689–695

    Article  PubMed  CAS  Google Scholar 

  3. Olanow CW (1993) A radical hypothesis for neurodegeneration. Trends Neurosci 16:439–444

    Article  PubMed  CAS  Google Scholar 

  4. Mate′s JM, Pe′rez-Go′mez C, Castro C (1999) Antioxidant enzymes and human diseases. Clin Biochem 32:595–603

    Article  Google Scholar 

  5. Alexi T, Borlongan CV, Faull RLM, Williams CE, Clark RG, Gluckman PD, Hughes PE (2000) Neuroprotective strategies for basal ganglia degeneration: Parkinson’s and Huntington’s diseases. Prog Neurobiol 60:409–470

    Article  PubMed  CAS  Google Scholar 

  6. Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine, 3rd edn. Oxford University Press, New York

    Google Scholar 

  7. Urano S, Asai Y, Makabe S, Matsuo M, Izumiyama N, Ohtsubo K, Endo T (1997) Oxidative injury of synapse and alteration of antioxidative defense systems in rats, and its prevention by vitamin E. Eur J Biochem 245:64–70

    Article  PubMed  CAS  Google Scholar 

  8. Yamamoto T, Yuki S, Watanabe T, Mitsuka M, Saito KI, Kogure K (1997) Delayed neuronal death prevented by inhibition of increased hydroxyl radical formation in a transient cerebral ischemia. Brain Res 762:240–242

    Article  PubMed  CAS  Google Scholar 

  9. Bastianetto S, Ramassamy C, Poirier J, Quiron R (1999) Dehydroepiandrosterone DHEA protects hippocampal cells from oxidative stress-induced damage. Brain Res Mol Brain Res 66:35–41

    Article  PubMed  CAS  Google Scholar 

  10. Blokland A, Jolles J (1993) Spatial learning deficit and reduced hippocampal ChAT activity in rats after an ICV injection of streptozotocin. Pharmacol Biochem Behav 44:491–494

    Article  PubMed  CAS  Google Scholar 

  11. Lannert H, Hoyer S (1998) Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav Neurosci 112:1199–1208

    Article  PubMed  CAS  Google Scholar 

  12. Chatterjee A, Prakashi SC (1997) The treatise on Indian medicinal plants, vol 5. National Institute of Science Communication, New Delhi, pp 99–100

    Google Scholar 

  13. Arora RB (1965) Nardostachys jatamansi—a chemical, pharmacological and clinical appraisal. Monograph Special Series, vol 51. ICMR, New Delhi

  14. Rastogi BR, Mehrotra K (1990) Compendium of Indian medicinal plants, 4th edn. Public Information Directorate, CSIR, New Delhi, pp 286–287

  15. Tripathi YB, Tripathi E, Upadhyaya A (1996) Antilipid peroxidative property of Nardostachys jatamansi. Indian J Exp Biol 34:1150–1161

    PubMed  CAS  Google Scholar 

  16. Joshi H, Parle M (2006) Nardostachys jatamansi improves learning and memory in mice. J Med Food 9:113–118

    Article  PubMed  Google Scholar 

  17. Ahmad M, Yousuf S, Khan MB, Hoda MN, Ahmad AS, Ansari MA, Ishrat T, Agrawal AK, Islam F (2006) Attenuation by Nardostachys jatamansi of 6-hydroxydopamine-induced Parkinsonism in rats: behavioral, neurochemical, and immunohistochemical studies. Pharmacol Biochem Behav 83:150–160

    Article  PubMed  CAS  Google Scholar 

  18. Salim S, Ahmad M, Zafar KS, Ahmad AS, Islam F (2003) Protective effect of Nardostachys jatamansi in rat cerebral ischemia. Pharmacol Biochem Behav 74:481–486

    Article  PubMed  CAS  Google Scholar 

  19. Singh A, Kumar A, Duggal S (2009) Nardostachys jatamansi DC. Potential herb with CNS effects. J Pharm Res Health Care 1:276–290

    CAS  Google Scholar 

  20. Rios JL, Recio MC, Ginger RM, Manz S (1996) An update review of saffron and its active constituents. Phytother Res 10:189–193

    Article  CAS  Google Scholar 

  21. Hosseinzadeh H, Khosravan V (2002) Anticonvulsant effects of aqueous and ethanolic extracts of Crocus sativus L. stigmas in mice. Arch Irn Med 5:44–47

    Google Scholar 

  22. Hosseinzadeh H, Younesi HM (2002) Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol 2:1–8

    Google Scholar 

  23. Hosseinzadeh H, Karimi G, Niapoor M (2004) Antidepressant effects of Crocus sativus stigma extracts and its constituents, crocin and safranal, in mice. Acta Hort ISHS 650:435–445

    CAS  Google Scholar 

  24. Abdullaev FJ (1993) Biological effects of saffron. Biofactors 4:83–86

    PubMed  CAS  Google Scholar 

  25. Escribano J, Alonso GL, Coca-Prados M, Fernandez JA (1996) Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett 100:23–30

    Article  PubMed  CAS  Google Scholar 

  26. Zhang YX, Sugiura M, Saito H, Shoyama Y (1994) Acute effects of Crocus sativus L. on passive avoidance performance in mice. Biol Pharmacol Bull 17:217–221

    Article  CAS  Google Scholar 

  27. Abe K, Sugiura M, Ymaguchi S, Shoyama Y, Saito H (1999) Saffron extract prevents acetaldehyde-induced inhibition of long-term potentiation in the rat dentate gyrus in vivo. Brain Res 851:287–289

    Article  PubMed  CAS  Google Scholar 

  28. Papandreou MA, Kanakis CD, Polissiou MG, Efthimiopoulos S, Cordopatis P, Margarity M, Lamari FN (2006) Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem 54:8762–8768

    Article  PubMed  CAS  Google Scholar 

  29. Ahmad AS, Ansari MA, Ahmad M, Saleem S, Yousuf S, Hoda MN, Islam F (2005) Neuroprotection by crocetin in a hemi-parkinsonian rat model. Pharmacol Biochem Behav 81:805–813

    Article  PubMed  CAS  Google Scholar 

  30. Schwarz K, Folz CM (1957) Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. Nutrition 15:255–264

    Google Scholar 

  31. Brauer AU, Savaskan NE (2004) Molecular actions of selenium in the brain: neuroprotective mechanisms of an essential trace element. Rev Neurosci 15:1–19

    Article  Google Scholar 

  32. Harman D (1993) Free radicals and age-related diseases. In: Pal YB (ed) Free radicals in aging. CRC Press, Boca Raton, pp 205–222

    Google Scholar 

  33. Lee SR, Bar-Noy S, Kwon J, Levine RL, Stadtman TC, Rhee SG (2000) Mammalian thioredoxin reductase: oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity. Proc Natl Acad Sci USA 97:2521–2526

    Article  PubMed  CAS  Google Scholar 

  34. Ishrat T, Parveen K, Khan MM, Khuwaja G, Khan MB, Yousuf S, Ahmad A, Shrivastav P, Islam F (2009) Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type. Brain Res 1281:117–127

    Article  PubMed  CAS  Google Scholar 

  35. Zafar KS, Siddiqui A, Sayeed I, Ahmad M, Salim S, Islam F (2003) Dose-dependent protective effect of selenium in rat model of Parkinson’s disease: neurobehavioral and neurochemical evidences. J Neurochem 84:438–446

    Article  PubMed  CAS  Google Scholar 

  36. Yousuf S, Atif F, Hoda N, Ahmad M, Saleem S, Ishrat T, Khan MB, Ahmad AS, Islam F (2007) Oral supplementation of Majun Baladar ameliorates antioxidant enzyme activities in cerebral ischaemic damage. Basic Clin Pharmacol Toxicol 101:246–453

    Article  PubMed  CAS  Google Scholar 

  37. Halliwell B, Gutteridge JMC (1984) Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet 1:1396–1397

    Article  PubMed  CAS  Google Scholar 

  38. Westermarck T, Santavouri P (1984) Principles of antioxidant therapy in neuronal ceroid lipofuscinosis. Med Biol 62:148–151

    PubMed  CAS  Google Scholar 

  39. Khan MB, Hoda MN, Yousuf S, Ishrat T, Ahmad M, Ahmad AS, Alavi SH, Haque N, Islam F (2006) Prevention of cognitive impairments and neurodegeneration by Khamira Abresham Hakim Arshad Wala. J Ethnopharmacol 108:68–73

    Article  PubMed  Google Scholar 

  40. Prabhu VM, Karandh SK, Rao A, Vidya PM, Sudhakar K (1994) Effect of Nardostachys jatamansi on biogenic amines and inhibitory amino acids on rat brain. Planta Med 60:114–217

    Article  PubMed  CAS  Google Scholar 

  41. Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, Ahmad AS, Islam F (2006) Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behav Brain Res 171:9–16

    Article  PubMed  CAS  Google Scholar 

  42. Olariu A, Tran MH, Yamada K, Mizuno M, Hefco V, Nabeshima T (2001) Memory deficits and increased emotionality induced by β-amyloid 25–35 are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus. J Neural Transm 108:1065–1079

    Article  PubMed  CAS  Google Scholar 

  43. Sharma M, Gupta YK (2003) Effect of alpha lipoic acid on intracerebroventricular streptozotocin model of cognitive impairment in rats. Eur Neuropsychopharm 13:241–247

    Article  CAS  Google Scholar 

  44. Morris R (1984) Development of the water maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60

    Article  PubMed  CAS  Google Scholar 

  45. Gallagher M, Burwell R, Burchinal M (1993) Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze. Behav Neurosci 107:618–626

    Article  PubMed  CAS  Google Scholar 

  46. Utely HC, Bernheim F, Hochslein P (1967) Effect of sulfhydryl reagent on peroxidation in microsome. Arch Biochem Biophys 118:29–32

    Article  Google Scholar 

  47. Islam F, Zia S, Sayeed I, Zafar KS, Ahmad AS (2002) Selenium induced alteration on lipids, lipid peroxidation, and thiol group in circadian rhythm centers of rat. Biol Trace Elem Res 90:1–12

    Article  Google Scholar 

  48. Jollow DJ, Mitchell JR, Zampagloine N, Gillete JR (1974) Bromobenzene-induced liver necrosis: protective role of glutathione and evidence for 3, 4- bromobenzene oxide as the hepatotoxic metabolite. Pharmacology 11:151–169

    Article  PubMed  CAS  Google Scholar 

  49. Mohandas J, Marshall JJ, Duggi GG, Horvath JS, Tiller D (1984) Differential distribution of glutathione and glutathione related enzymes in rabbit kidneys: possible implication in analgesic neuropathy. Cancer Res 44:5086–5091

    PubMed  CAS  Google Scholar 

  50. Habig WH, Pabst MJ, Jokoby B (1974) Glutathion-S-transferase: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    PubMed  CAS  Google Scholar 

  51. Athar M, Mukhtar H, Bickers DR, Khan IU, Kalyanaraman B (1989) Evidence for the metabolism of tumor promoter organic hydroperoxides into free radicals by human carcinoma skin keratinocytes: an ESR-spin trapping study. Carcinogenesis 10:1499–1503

    Article  PubMed  CAS  Google Scholar 

  52. Stevens MJ, Obrosova I, Cao X, Van Huysen C, Greene DA (2000) Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy. Diabetes 49:1006–1015

    Article  PubMed  CAS  Google Scholar 

  53. Claiborne A (1985) Catalase activity. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 283–284

    Google Scholar 

  54. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  55. Zs-Nagy I (1978) A membrane hypothesis of aging. J Theor Biol 75:189–195

    Article  PubMed  CAS  Google Scholar 

  56. Zs-Nagy I (1990) Dietary antioxidants and brain aging: hopes and facts. In: Ingram DK, Baker GT, Shock NW (eds) The potential for nutritional modulation of aging processes. Food and Nutrition Press, Trumbell, pp 379–399

    Google Scholar 

  57. Blokland A (1995) Acetylcholine: a neurotransmitter for learning and memory. Brain Res Brain Res Rev 21:285–300

    Article  PubMed  CAS  Google Scholar 

  58. Nitsch R, Hoyer S (1991) Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. Neurosci Lett 128:199–202

    Article  PubMed  CAS  Google Scholar 

  59. Hoyer S, Hennenberg N, Knapp S, Lannert H, Martin E (1996) Brain glucose metabolism is controlled by amplification and desensitization of the neuronal insulin receptor. Ann NY Acad Sci 777:374–379

    Article  PubMed  CAS  Google Scholar 

  60. Hoyer S (2000) Brain glucose and energy metabolism abnormalities in sporadic Alzheimer disease causes and consequences: an update. Exp Gerontol 35:1363–1372

    Article  PubMed  CAS  Google Scholar 

  61. Watt F (1996) Nuclear microscope analysis in Alzheimer’s and Parkinson’s disease: a review. Cell Mol Biol 42:17–26

    PubMed  CAS  Google Scholar 

  62. Mattson MP, Chan SL (2001) Dysregulation of cellular calcium homeostasis in Alzheimer’s disease: bad genes and bad habits. J Mol Neurosci 17:205–224

    Article  PubMed  CAS  Google Scholar 

  63. Arlt S, Beisiegel U, Kontush A (2002) Lipid peroxidation in neurodegeneration: new insights into Alzheimer’s disease. Curr Opin Lipidol 13:289–294

    Article  PubMed  CAS  Google Scholar 

  64. Ansari MA, Ahmad AS, Ahmad M, Salim S, Yousuf S, Ishrat T, Islam F (2004) Selenium protects cerebral ischemia in rat brain mitochondria. Biol Trace Elem Res 101:73–86

    Article  PubMed  CAS  Google Scholar 

  65. Ahmad AS, Zia S, Sayeed I, Ansari MA, Ahmad M, Salim S, Yousuf S, Islam F (2005) Sodium selenite stimulates neurobehavior and neurochemical activities in rats. Biol Trace Elem Res 103:59–68

    Article  PubMed  CAS  Google Scholar 

  66. Li P, Yamakuni T, Matsunaga K, Kondo S, Ohizumi Y (2003) Nardosinone enhances nerve growth factor-induced neurite outgrowth in a mitogen-activated protein kinase- and protein kinase C-dependent manner in PC12D cells. J Pharmacol Sci 93:122–125

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are thankful to the Department of Ayurveda, Yoga and Naturopathy, Unani Siddha and Homeopathy (AYUSH) and the Ministry of Health and Family Welfare, Government of India, for financial assistance. The authors are thankful to Mr. Dharamvir and late Mr. Anil Kumar for help and cooperation.

Conflict of interest

We have no conflict of interest and certify hereby that this work has never been published.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to M. Badruzzaman Khan or Fakhrul Islam.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khan, M.B., Hoda, M.N., Ishrat, T. et al. Neuroprotective efficacy of Nardostachys jatamansi and crocetin in conjunction with selenium in cognitive impairment. Neurol Sci 33, 1011–1020 (2012). https://doi.org/10.1007/s10072-011-0880-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-011-0880-1

Keywords

Navigation