Skip to main content

Advertisement

SpringerLink
Log in

Kolaviron, a Garcinia kola Biflavonoid Complex, Protects Against Ischemia/Reperfusion Injury: Pertinent Mechanistic Insights from Biochemical and Physical Evaluations in Rat Brain

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

Abstract

The pathophysiology of stroke is characterized by biochemical and physical alterations in the brain. Modulation of such aberrations by therapeutic agents affords insights into their mechanism of action. Incontrovertible evidences that oxidative stress is involved in the pathophysiology of neurologic disorders have brought antioxidative compounds, especially plant phytochemicals, under increasing focus as potential remedies for the prevention and management of neurodegenerative diseases. Kolaviron, a biflavonoid complex isolated from Garcinia kola Heckel (Guttiferae) was evaluated for neuroprotectivity in brains of male Wistar rats submitted to bilateral common carotid artery occlusion-induced global ischemia/reperfusion injury (I/R). Animals were divided into six groups: sham treated, vehicle (I/R), 50 mg/kg kolaviron + I/R, 100 mg/kg kolaviron + I/R, 200 mg/kg kolaviron + I/R and quercetin (20 mg/kg i.p.) + I/R. The common carotid arteries were occluded for 30 min followed by 2 h of reperfusion. Relative brain weight and brain water content were determined and oxidative stress and neurochemical markers were also evaluated. I/R caused significant decreases in glutathione level and the activities of enzymic antioxidants, the sodium pump and acetylcholinesterase while significant increases were recorded in relative brain weight, brain water content, lipid peroxidation and the activities of glutamine synthetase and myeloperoxidase. There was a remarkable ablation of I/R induced oxidative stress, neurochemical aberrations and brain edema in animals pretreated with kolaviron. The results suggested that the protection afforded by kolaviron probably involved regulation of redox and electrolyte homeostasis as well as anti-inflammatory and antiexcitotoxic mechanisms.

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

Similar content being viewed by others

References

  1. Eastman P (2003) Why neuroprotective drugs fail: question about cell death present new challenges. Neurol Today 3:18–19

    Article  Google Scholar 

  2. Gupta YK, Briyal S, Gulati A (2010) Therapeutic potential of herbal drugs in cerebral ischemia. Indian J Physiol Pharmacol 54:99–122

    CAS  PubMed  Google Scholar 

  3. Miniño AM, Xu J, Kochanek KD (2010) Deaths: preliminary data for 2008. Natl Vital Stat Rep 59:1–52

    PubMed  Google Scholar 

  4. Towfighi A, Saver JL (2011) Stroke declines from third to fourth leading cause of death in the US: historical perspective and challenges ahead. Stroke 42:2351–2355

    Article  PubMed  Google Scholar 

  5. Shigehatake Y, Yokota C, Amano T et al (2014) Stroke education using an animated cartoon and a manga for junior high school students. J Stroke Cerebrovasc Dis 23:1623–1627

    Article  PubMed  Google Scholar 

  6. Fang MC, Coca Perraillon M, Ghosh K et al (2014) Trends in stroke rates, risk, and outcomes in the US, 1988–2008. Am J Med 127:608–615

    Article  PubMed  Google Scholar 

  7. Hankey GJ (2014) Secondary stroke prevention. Lancet Neurol 13:178–194

    Article  PubMed  Google Scholar 

  8. Ahmed MAE, El Morsy EM, Ahmed AAE (2014) Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats. Life Sci 110:61–69

    Article  CAS  PubMed  Google Scholar 

  9. Qu X, Qi D, Dong F et al (2014) Quercetin improves hypoxia-ischemia induced cognitive deficits via promoting remyelination in neonatal rat. Brain Res 1553:31–40

    Article  CAS  PubMed  Google Scholar 

  10. Iwu M, Igboko O (1982) Flavonoids of Garcinia kola Seeds. J Nat Prod 45:650–651

    Article  CAS  Google Scholar 

  11. EO Farombi (2003) Locally derived natural antioxidant substances in Nigeria: potential role as new chemotherapeutic agents. In: T. Theeshan Bahorun, Gurib-Fakim (eds.) Molecular and therapeutic aspects of redox biochemistry. OICA International (UK) Limited, London pp 207–226

  12. Adedara IA, Awogbindin IO, Anamelechi JP, Farombi EO (2014) Garcinia kola seed ameliorates renal, hepatic, and testicular oxidative damage in streptozotocin-induced diabetic rats. Pharm Biol. doi:10.3109/13880209.2014.937504

    PubMed  Google Scholar 

  13. Farombi EO (2000) Mechanisms for the hepatoprotective action of kolaviron: studies on hepatic enzymes, microsomal lipids and lipid peroxidation in carbontetrachloride-treated rats. Pharmacol Res 42:75–80

    Article  CAS  PubMed  Google Scholar 

  14. Farombi EO, Tahnteng JG, Agboola AO et al (2000) Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron–a Garcinia kola seed extract. Food Chem Toxicol 38:535–541

    Article  CAS  PubMed  Google Scholar 

  15. Farombi EO, Adepoju BF, Ola-Davies OE, Emerole GO (2005) Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural bioflavonoid of Garcinia kola seeds. Eur J Cancer Prev 14:207–214

    Article  CAS  PubMed  Google Scholar 

  16. Farombi EO, Alabi MC, Akuru TO (2002) Kolaviron modulates cellular redox status and impairment of membrane protein activities induced by potassium bromate (KBrO(3)) in rats. Pharmacol Res 45:63–68

    Article  PubMed  Google Scholar 

  17. Farombi EO, Abarikwu SO, Adedara IA, Oyeyemi MO (2007) Curcumin and kolaviron ameliorate di-n-butylphthalate-induced testicular damage in rats. Basic Clin Pharmacol Toxicol 100:43–48

    Article  CAS  PubMed  Google Scholar 

  18. Adaramoye OA, Akanni OO, Farombi EO (2013) Nevirapine induces testicular toxicity in Wistar rats: reversal effect of kolaviron (biflavonoid from Garcinia kola seeds). J Basic Clin Physiol Pharmacol 24:313–320

    Article  CAS  PubMed  Google Scholar 

  19. Adedara IA, Vaithinathan S, Jubendradass R, Mathur PP, Farombi EO (2013) Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats. Environ Toxicol Pharmacol 35:444–453

    Article  CAS  PubMed  Google Scholar 

  20. Adaramoye OA, Lawal SO (2014) Kolaviron, a biflavonoid fraction from Garcinia kola, protects against isoproterenol-induced injury by mitigating cardiac dysfunction and oxidative stress in rats. J Basic Clin Physiol Pharmacol. doi:10.1515/jbcpp-2013-0139

    Google Scholar 

  21. Nwankwo JO, Tahnteng JG, Emerole GO (2000) Inhibition of aflatoxin B1 genotoxicity in human liver-derived HepG2 cells by kolaviron biflavonoids and molecular mechanisms of action. Eur J Cancer Prev 9:351–361

    Article  CAS  PubMed  Google Scholar 

  22. Abarikwu SO, Farombi EO, Kashyap MP, Pant AB (2011) Kolaviron protects apoptotic cell death in PC12 cells exposed to atrazine. Free Radic Res 45:1061–1073

    Article  CAS  PubMed  Google Scholar 

  23. Abarikwu SO, Farombi EO, Pant AB (2012) Kolaviron biflavanoids of Garcinia kola seeds protect atrazine-induced cytotoxicity in primary cultures of rat Leydig cells. Int J Toxicol 31:407–415

    Article  CAS  PubMed  Google Scholar 

  24. Abarikwu SO (2014) Kolaviron, a natural flavonoid from the seeds of Garcinia kola, reduces LPS-induced inflammation in macrophages by combined inhibition of IL-6 secretion, and inflammatory transcription factors, ERK1/2, NF-κB, p38, Akt, p-c-JUN and JNK. Biochim Biophys Acta 1840:2373–2381

    Article  CAS  PubMed  Google Scholar 

  25. Iwu MM (1985) Antihepatoxic constituents of Garcinia kola seeds. Experientia 41:699–700

    Article  CAS  PubMed  Google Scholar 

  26. Farombi EO, Shrotriya S, Surh Y-J (2009) Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-kappaB and AP-1. Life Sci 84:149–155

    Article  CAS  PubMed  Google Scholar 

  27. Mansoorali KP, Prakash T, Kotresha D et al (2012) Cerebroprotective effect of Eclipta alba against global model of cerebral ischemia induced oxidative stress in rats. Phytomedicine 19:1108–1116

    Article  CAS  PubMed  Google Scholar 

  28. Farbiszewski R, Bielawski K, Bielawska A, Sobaniec W (1995) Spermine protects in vivo the antioxidant enzymes in transiently hypoperfused rat brain. Acta Neurobiol Exp (Wars) 55:253–258

    CAS  Google Scholar 

  29. Fotheringham AP, Davies CA, Davies I (2000) Oedema and glial cell involvement in the aged mouse brain after permanent focal ischaemia. Neuropathol Appl Neurobiol 26:412–423

    Article  CAS  PubMed  Google Scholar 

  30. Mishra V, Verma R, Raghubir R (2010) Neuroprotective effect of flurbiprofen in focal cerebral ischemia: the possible role of ASIC1a. Neuropharmacology 59:582–588

    Article  CAS  PubMed  Google Scholar 

  31. Saad MA, Abdelsalam RM, Kenawy SA, Attia AS (2014) Montelukast, a cysteinyl leukotriene receptor-1 antagonist protects against hippocampal injury induced by transient global cerebral ischemia and reperfusion in rats. Neurochem Res. doi:10.1007/s11064-014-1478-9

    PubMed  Google Scholar 

  32. Weichselbaum TE (1946) An accurate and rapid method for determination of proteins in small amounts of blood serum and plasma. Am J Clin Pathol 16:40–49

    Google Scholar 

  33. Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: the FRAP assay. Anal Biochem 239:70–76

    Article  CAS  PubMed  Google Scholar 

  34. Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  PubMed  Google Scholar 

  35. Rotruck JT, Pope AL, Ganther HE et al (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590

    Article  CAS  PubMed  Google Scholar 

  36. Misra HP, Fridovich I (1972) The univalent reduction of oxygen by reduced flavins and quinones. J Biol Chem 247:188–192

    CAS  PubMed  Google Scholar 

  37. Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394

    Article  CAS  PubMed  Google Scholar 

  38. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  39. Ellman GL, Courtney KD, Andres V, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  40. Svoboda P, Mosinger B (1981) Catecholamines and the brain microsomal Na, K-adenosinetriphosphatase—I. Protection against lipoperoxidative damage. Biochem Pharmacol 30:427–432

    Article  CAS  PubMed  Google Scholar 

  41. Sunil AG, Kesavanarayanan KS, Kalaivani P et al (2011) Total oligomeric flavonoids of Cyperus rotundus ameliorates neurological deficits, excitotoxicity and behavioral alterations induced by cerebral ischemic-reperfusion injury in rats. Brain Res Bull 84:394–405

    Article  CAS  PubMed  Google Scholar 

  42. Sadasivam S, Manickam A (2003) Biochemical methods, 2nd ed. New Delhi

  43. Eiserich JP, Hristova M, Cross CE et al (1998) Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 391:393–397

    Article  CAS  PubMed  Google Scholar 

  44. Ozkul A, Sair A, Akyol A et al (2014) Effects of lithium and lamotrigine on oxidative-nitrosative stress and spatial learning deficit after global cerebral ischemia. Neurochem Res 39:853–861

    Article  CAS  PubMed  Google Scholar 

  45. Durukan A, Tatlisumak T (2007) Acute ischemic stroke: overview of major experimental rodent models, pathophysiology, and therapy of focal cerebral ischemia. Pharmacol Biochem Behav 87:179–197

    Article  CAS  PubMed  Google Scholar 

  46. Wang J, Jin H, Hua Y et al (2012) Role of protease-activated receptor-1 in brain injury after experimental global cerebral ischemia. Stroke 43:2476–2482

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Radenovic L, Selakovic V, Olivan S et al (2014) Neuroprotective efficiency of tetanus toxin C fragment in model of global cerebral ischemia in Mongolian gerbils. Brain Res Bull 101(37–44):48

    Google Scholar 

  48. Martin RL, Lloyd HG, Cowan AI (1994) The early events of oxygen and glucose deprivation: setting the scene for neuronal death? Trends Neurosci 17:251–257

    Article  CAS  PubMed  Google Scholar 

  49. Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397

    Article  CAS  PubMed  Google Scholar 

  50. Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568

    CAS  PubMed  Google Scholar 

  51. Ozkul A, Akyol A, Yenisey C et al (2007) Oxidative stress in acute ischemic stroke. J Clin Neurosci 14:1062–1066

    Article  CAS  PubMed  Google Scholar 

  52. Homi HM, Freitas JJS, Curi R et al (2002) Changes in superoxide dismutase and catalase activities of rat brain regions during early global transient ischemia/reperfusion. Neurosci Lett 333:37–40

    Article  CAS  PubMed  Google Scholar 

  53. Breckwoldt MO, Chen JW, Stangenberg L et al (2008) Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase. Proc Natl Acad Sci USA 105:18584–18589

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Park JH, Kyu PO, Cho JH et al (2014) Anti-inflammatory effect of tanshinone I in neuroprotection against cerebral ischemia-reperfusion injury in the gerbil hippocampus. Neurochem Res 39:1300–1312

    Article  CAS  PubMed  Google Scholar 

  55. Guo H, Li M, Liu Q et al (2014) Danhong injection attenuates ischemia/reperfusion-induced brain damage which is associating with Nrf2 levels in vivo and in vitro. Neurochem Res 39:1817–1824

    Article  CAS  PubMed  Google Scholar 

  56. Collino M, Aragno M, Mastrocola R et al (2006) Modulation of the oxidative stress and inflammatory response by PPAR-gamma agonists in the hippocampus of rats exposed to cerebral ischemia/reperfusion. Eur J Pharmacol 530:70–80

    Article  CAS  PubMed  Google Scholar 

  57. Read SJ, Hirano T, Davis SM, Donnan GA (1999) Limiting neurological damage after stroke: a review of pharmacological treatment options. Drugs Aging 14:11–39

    Article  CAS  PubMed  Google Scholar 

  58. Erecińska M, Silver IA (2001) Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol 128:263–276

    Article  PubMed  Google Scholar 

  59. Saito A, Maier CM, Narasimhan P et al (2005) Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Mol Neurobiol 31:105–116

    Article  CAS  PubMed  Google Scholar 

  60. Adibhatla RM, Hatcher JF (2008) Altered lipid metabolism in brain injury and disorders. Subcell Biochem 49:241–268

    Article  PubMed Central  PubMed  Google Scholar 

  61. Koner BC, Banerjee BD, Ray A (1998) Organochlorine pesticide-induced oxidative stress and immune suppression in rats. Indian J Exp Biol 36:395–398. as new chemotherapeutic agents. In: Theeshan Bahorun, T., Gurib-Fakim A (Eds.) Molecular and Therapeutic Aspects of Redox Biochemistry. OICA International (UK) Limited, London pp 207–226

  62. Tuna M, Polat S, Erman T et al (2001) Effect of anti-rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5′-triphosphatase and superoxide dismutase activation, and ultrastructural changes. J Neurosurg 95:64–73

    CAS  PubMed  Google Scholar 

  63. Mrsić-Pelcić J, Pelcić G, Vitezić D et al (2004) Hyperbaric oxygen treatment: the influence on the hippocampal superoxide dismutase and Na + , K + -ATPase activities in global cerebral ischemia-exposed rats. Neurochem Int 44:585–594

    Article  PubMed  Google Scholar 

  64. Zhao T, Zhang X, Zhao Y et al (2014) Pretreatment by evodiamine is neuroprotective in cerebral ischemia: up-regulated pAkt, pGSK3β, down-regulated NF-κB expression, and ameliorated BBB permeability. Neurochem Res 39:1612–1620

    Article  CAS  PubMed  Google Scholar 

  65. Farombi EO, Adedara IA, Ajayi BO et al (2013) Kolaviron, a natural antioxidant and anti-inflammatory phytochemical prevents dextran sulphate sodium-induced colitis in rats. Basic Clin Pharmacol Toxicol 113:49–55

    Article  CAS  PubMed  Google Scholar 

  66. Iwu MM (1986) Biflavanones of Garcinia: pharmacological and biological activities. Prog Clin Biol Res 213:485–488

    CAS  PubMed  Google Scholar 

  67. Chelluboina B, Klopfenstein JD, Pinson DM et al (2014) Stem cell treatment after cerebral ischemia regulates the gene expression of apoptotic molecules. Neurochem Res 39:1511–1521

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Author information

Author notes

  1. Afolabi C. Akinmoladun

    Present address: Ciencias Biologicas-biofisica, Instituto de Biofisica Carlos Chagas Filho (IBCCF), Universidade Federal do Rio de Janeiro (UFRJ), Centro de Ciencias da Saude, Bloco G, Cidade Universitaria, Rio de Janeiro, CEP: 21941-902, Brazil

Authors and Affiliations

  1. Department of Biochemistry, The Federal University of Technology, School of Sciences, Akure, Nigeria

    Afolabi C. Akinmoladun, Bolanle L. Akinrinola & M. Tolulope Olaleye

  2. Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria

    Ebenezer O. Farombi

Authors
  1. Afolabi C. Akinmoladun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bolanle L. Akinrinola
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Tolulope Olaleye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ebenezer O. Farombi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Afolabi C. Akinmoladun.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Akinmoladun, A.C., Akinrinola, B.L., Olaleye, M.T. et al. Kolaviron, a Garcinia kola Biflavonoid Complex, Protects Against Ischemia/Reperfusion Injury: Pertinent Mechanistic Insights from Biochemical and Physical Evaluations in Rat Brain. Neurochem Res 40, 777–787 (2015). https://doi.org/10.1007/s11064-015-1527-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1527-z

Keywords

Search

Navigation