Landolphia owariensis Attenuates Alcohol-induced Cerebellar Neurodegeneration: Significance of Neurofilament Protein Alteration in the Purkinje Cells

Open access


Background: Alcohol-induced cerebellar neurodegeneration is a neuroadaptation that is associated with chronic alcohol abuse. Conventional drugs have been largely unsatisfactory in preventing neurodegeneration. Yet, multimodal neuro-protective therapeutic agents have been hypothesised to have high therapeutic potential for the treatment of CNS conditions; there is yet a dilemma of how this would be achieved. Contrarily, medicinal botanicals are naturally multimodal in their mechanism of action.

Aim: The effect of L. owariensis was therefore assessed in alcohol-induced neurodegeneration of the cerebellar cortex in rats.

Materials and methods: Two groups of rats were oro-gastrically fed thrice daily with 5 g/kg ethanol (25% w/v), and 5 g/kg ethanol (25% w/v) plus L. owariensis (100 mg/kg body weight) respectively in diluted nutritionally complete diet (50% v/v). A control group was correspondingly fed a nutritionally complete diet (50% v/v) made isocaloric with glucose. Cytoarchitectural study of the cerebellar cortex was examined with H&E. Immunocytochemical analysis was carried out with the use of monoclonal antibody anti-NF in order to detect alterations in the neuronal cytoskeleton.

Results: After 4 days of binge alcohol treatment, we observed that L. owariensis supplementation significantly lowered the levels of histologic and biochemical indices of neurodegeneration. The level of neurodegeneration and cytoarchitecture distortion of the cerebellar cortex of rats exposed to ethanol was reduced by L. owariensis. Neurofilament-immunoreactivity (NF-IR) was evoked in the Purkinje cells of rats that received L. owariensis supplement.

Conclusions: L. owariensis attenuates alcohol-induced cerebellar degeneration in the rat by alleviating oxidative stress and alteration of NF protein expression in the Purkinje cells.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Harper C. The neuropathology of alcohol-related brain damage. Alcohol 2009;44(2):136-40.

  • 2. Barsottini OG Albuquerque MV Braga-Nofo P et al. Adult onset sporadic ataxias: a diagnostic challenge. Arq de Neuro-psiquiatr 2014;72(3):232-40.

  • 3. Davis LE King MK Schultz JL. Fundamentals of neurologic disease. New York NY: Demos Medical Publishing; 2005.

  • 4. Yokota O Tsuchiya K Terada S et al. Frequency and clinicopathological characteristics of alcoholic cerebellar degeneration in Japan: a cross-sectional study of 1509 postmortems. Acta Neuropathol 2006;112:43-51.

  • 5. Jaatinen P Rintala J. Mechanisms of ethanol-induced degeneration in the developing mature and aging cerebellum. Cerebellum 2008;7:332-47.

  • 6. Andersen BB. Reduction of Purkinje cell volume in cerebellum of alcoholics. Brain research 2004;1007(1):10-8.

  • 7. Obernier JA White AM Swartzwelder HS et al. Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats. Pharmacol Biochem Behav 2002;72(3):521-32.

  • 8. Hermens DF Lagopoulos J Tobias-Webb J et al. Pathways to alcohol-induced brain impairment in young people: a review. Cortex 2013;49(1):3-17.

  • 9. McQueeny T Schweinsburg BC Schweinsburg AD et al. Altered white matter integrity in adolescent binge drinkers. Alcohol Clin Exp Res 2009;33(7):1278-85.

  • 10. Parry-Jones BL Vaughan FL Miles CW. Traumatic brain injury and substance misuse: a systematic review of prevalence and outcomes research (1994–2004). Neuropsychol Rehabil 2006;16(5):537-60.

  • 11. Litten RZ Egli M Heilig M et al. Medications development to treat alcohol dependence: a vision for the next decade. Addiction Biology 2012;17(3):513-27.

  • 12. Mechanick JI Zhao S Merrill WC. Dietary supplements and nutraceuticals. In: Mechanick JI Michael Via Zhao S editors. Molecular Nutrition: The Practical Guide. The Endocrine Society 2015:80-118.

  • 13. Thuret S Moon LD Gage FH. Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 2006;7:628-43.

  • 14. Pointillart V Petitjean ME Wiart L et al. Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 2000;38:71-6.

  • 15. Thomsen GM Gowing G Svendsen S et al. The past present and future of stem cell clinical trials for ALS. Experimental neurology 2014;262:127-37.

  • 16. Yu D Thakor D K Han I et al. Alleviation of chronic pain following rat spinal cord compression injury with multimodal actions of huperzine A. Proc Natl Acad Sci USA 2013;110(8):E746–E755.

  • 17. Shen J Xu X Cheng F et al. Virtual screening on natural products for discovering active compounds and target information. Current Medicinal Chemistry 2003;10(21):2327-42.

  • 18. Okonkwo TJ Osadebe PO. Isolation and characterization of potential bioactive compounds from L. owariensis P. Beauv Stringy Seed Pulp. International Journal of Applied Research in Natural Products 2013;6(3):28-38.

  • 19. Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol 1983;54:275-87.

  • 20. Hsu SM Raine L Fanger H. Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981;29:577-80.

  • 21. Gutteridge JM Wilkins S. Copper-dependent hydroxyl radical damage to ascorbic acid: Formation of a thiobarbituric acid-reactive product. FEBS Lett. 1982;137:327-40.

  • 22. Yonguc GN Ozdemir MB Kucukatay V et al: Memory function and total pyramidal neuron number of hippocampus in streptozotocin induced diabetic rats. J Neurol Sci (Turk) 2014;31:461–73.

  • 23. Noorafshan A Rashidiani-Rashidabadi A Karbalay-Doust S et al. Curcumin can prevent the changes in cerebellar structure and function induced by sodium metabisulfite in rat. Experimental Neurobiology 2013;22(4):258-67.

  • 24. Salavati P Ramezani M Monsef-Esfahani HR et al. Neuroprotective effect of total and sequential extract of Scrophularia striata Boiss. in rat cerebellar granule neurons following glutamate-induced neurotoxicity: an in-vitro study. Iran J Pharm Res 2013;12(2):389-94.

  • 25. Uttara B Singh AV Zamboni P et al. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Current Neuropharmacology 2009;7(1):65.

  • 26. Shan LQ Ma S Qiu XC et al. Hydroxysafflor Yellow A protects spinal cords from ischemia/reperfusion injury in rabbits. BMC neuroscience. 2010;11(1):98.

  • 27. Jovanovic Z. Antioxidative defense mechanisms in the aging brain. Archives of Biological Sciences 2014;66(1):245-52.

  • 28. Liu Q Xie F Alvarado-Diaz A et al. Neurofilamentopathy in neurodegenerative diseases. The Open Neurology Journal 2011;5:58-62.

  • 29. Yuan A Rao MV Nixon RA. Neurofilaments at a glance. Journal of Cell Science 2012;125(14):257-63.

  • 30. Redondo J Kemp K Hares K et al. Purkinje cell pathology and loss in multiple sclerosis cerebellum. Brain Pathology 2015;25(6):692-700.

Journal information
Impact Factor

CiteScore 2018: 0.587

SCImago Journal Rank (SJR) 2018: 0.311

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 221 115 3
PDF Downloads 123 69 2