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Neuroprotective Effect of Farnesol Against Rotenone Induced Parkinson’s Disease in Drosophila Melanogaster

Year 2023, Volume: 43 Issue: 1, 15 - 21, 01.03.2023

Jayaram Saravanan Praveen Thaggikuppe Krishnamurthy

https://doi.org/10.52794/hujpharm.1080352

Abstract

The current study aimed to investigate the neuroprotective effects of farnesol on rotenone-induced neurotoxicity in Drosophila melanogaster. Neurotoxicity was induced in Drosophila melanogaster by administering 500 μmol of rotenone and then the flies were administered either 300 μmol or 600 μmol of farnesol in the diet for the duration of the experiment. The study measured the effect of farnesol on longevity through a survival rate study, and locomotor function through a negative geotaxis assay. In addition, the study also estimated in vivo antioxidant parameters to determine the impact of farnesol on oxidative stress. The results showed that farnesol improved both longevity and locomotor function in the flies treated with 300 μmol or 600 μmol of test compound compared to control. The antioxidant studies also demonstrated that farnesol enhanced the catalase and superoxide dismutase activity and decreased lipid peroxidation. Based on these findings, it is concluded that farnesol might exhibit a significant neuroprotective effect against Parkinson’s disease.

Keywords

Farnesol Drosophila melanogaster negative geotaxis survival rate antioxidants

References

  • [1] Jankovic J. Parkinson’s disease: Clinical features and diagnosis. Journal of Neurology, Neurosurgery and Psychiatry 2008;79:368–76. https://doi.org/10.1136/jnnp.2007.131045.
  • [2] Guo JD, Zhao X, Li Y, Li GR, Liu XL. Damage to dopaminergic neurons by oxidative stress in Parkinson’s disease (Review). International Journal of Molecular Medicine 2018;41:1817–25. https://doi.org/10.3892/ijmm.2018.3406.
  • [3] Chen C, Turnbull DM, Reeve AK. Mitochondrial dysfunction in Parkinson’s disease—cause or consequence? Biology 2019;8:1–26. https://doi.org/10.3390/biology8020038.
  • [4] Ebrahimi-Fakhari D, Wahlster L, McLean PJ. Protein degradation pathways in Parkinson’s disease: Curse or blessing. Acta Neuropathologica 2012;124:153–72. https://doi.org/10.1007/s00401-012-1004-6.
  • [5] Zaichick S v., McGrath KM, Caraveo G. The role of Ca2+ signaling in Parkinson’s disease. DMM Disease Models and Mechanisms 2017;10:519–35. https://doi.org/10.1242/dmm.028738.
  • [6] Wang T, Zhang W, Pei Z, Block M, Wilson B, Reece JM, et al. Reactive microgliosis participates in MPP + ‐induced dopaminergic neurodegeneration: role of 67 kDa laminin receptor . The FASEB Journal 2006;20:906–15. https://doi.org/10.1096/fj.05-5053com.
  • [7] Hwang O. Role of Oxidative Stress in Parkinson’s Disease. Experimental Neurobiology 2013;22:11–7. https://doi.org/10.5607/en.2013.22.1.11.
  • [8] Cacabelos R. Parkinson’s disease: From pathogenesis to pharmacogenomics. International Journal of Molecular Sciences 2017;18. https://doi.org/10.3390/ijms18030551.
  • [9] Puspita L, Chung SY, Shim JW. Oxidative stress and cellular pathologies in Parkinson’s disease. Molecular Brain 2017;10. https://doi.org/10.1186/s13041-017-0340-9.
  • [10] Lisha J, Saravanana J, Santilna KS, Praveen TK, Rajkumar P, Wadhwani AD, et al. Neuroprotective activity of farnesol against bilateral common carotid artery occlusion induced cerebral ischemia/reperfusion injury in mice. Latin American Journal of Pharmacy 2019;38:572–8.
  • [11] Jung YY, Hwang ST, Sethi G, Fan L, Arfuso F, Ahn KS. Potential anti-inflammatory and anti-cancer properties of farnesol. Molecules 2018;23:1–15. https://doi.org/10.3390/molecules23112827.
  • [12] Qamar W, Sultana S. Farnesol ameliorates massive inflammation, oxidative stress and lung injury induced by intratracheal instillation of cigarette smoke extract in rats: An initial step in lung chemoprevention. Chemico-Biological Interactions 2008;176:79–87. https://doi.org/10.1016/j.cbi.2008.08.011.
  • [13] Burke YD, Stark MJ, Roach SL, Sen SE, Crowell PL. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Lipids 1997;32:151–6. https://doi.org/10.1007/s11745-997-0019-y.
  • [14] Jahangir T, Khan TH, Prasad L, Sultana S. Farnesol prevents Fe-NTA-mediated renal oxidative stress and early tumour promotion markers in rats. Human and Experimental Toxicology 2006;25:235–42. https://doi.org/10.1191/0960327106ht616oa.
  • [15] Hirth F. Drosophila melanogaster in the Study of Human Neurodegeneration. CNS & Neurological Disorders Drug Targets 2010;9:504. https://doi.org/10.2174/187152710791556104.
  • [16] Coulom H, Birman S. Chronic exposure to rotenone models sporadic Parkinson’s disease in Drosophila melanogaster. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 2004;24:10993–8. https://doi.org/10.1523/JNEUROSCI.2993-04.2004.
  • [17] Ambegaokar SS, Roy B, Jackson GR. Neurodegenerative models in Drosophila: polyglutamine disorders, Parkinson disease, and amyotrophic lateral sclerosis. Neurobiology of Disease 2010;40:29–39. https://doi.org/10.1016/J.NBD.2010.05.026.
  • [18] Lakkappa N, Krishnamurthy PT, Pandareesh MD, Hammock BD, Hwang SH. Soluble epoxide hydrolase inhibitor, APAU, protects dopaminergic neurons against rotenone induced neurotoxicity: Implications for Parkinson’s disease. NeuroToxicology 2019;70:135–45. https://doi.org/10.1016/j.neuro.2018.11.010.
  • [19] Hosamani R, Ramesh SR, Muralidhara. Attenuation of rotenone-induced mitochondrial oxidative damage and neurotoxicty in drosophila melanogaster supplemented with creatine. Neurochemical Research 2010;35:1402–12. https://doi.org/10.1007/s11064-010-0198-z.
  • [20] Wongchum N, Dechakhamphu A. Ethanol extract of Cassia siamea L. increases life span in Drosophila melanogaster. Biochemistry and Biophysics Reports 2021;25. https://doi.org/10.1016/j.bbrep.2021.100925.
  • [21] Hosamani R, Muralidhara. Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster. NeuroToxicology 2009;30:977–85. https://doi.org/10.1016/j.neuro.2009.08.012.
  • [22] Ohkawa H, Ohishi N, Yagi K. Reaction of linoleic acid hydroperoxide with thiobarbituric acid. Undefined 1978.
  • [23] Masuoka N, Wakimoto M, Ubuka T, Nakano T. Spectrophotometric determination of hydrogen peroxide: Catalase activity and rates of hydrogen peroxide removal by erythrocytes. Clinica Chimica Acta 1996;254:101–12. https://doi.org/10.1016/0009-8981(96)06374-7.
  • [24] MARKLUND S, MARKLUND G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry 1974;47:469–74. https://doi.org/10.1111/J.1432-1033.1974.TB03714.X.
  • [25] Smith GA, Heuer A, Dunnett SB, Lane EL. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: predicting l-DOPA-induced dyskinesia. Behavioural Brain Research 2012;226:281–92. https://doi.org/10.1016/J.BBR.2011.09.025.
  • [26] Bargiotas P, Konitsiotis S. Levodopa-induced dyskinesias in Parkinson’s disease: emerging treatments. Neuropsychiatric Disease and Treatment 2013;9:1605. https://doi.org/10.2147/NDT.S36693.
  • [27] Calou I, Bandeira MA, Aguiar-Galvão W, Cerqueira G, Siqueira R, Neves KR, et al. Neuroprotective Properties of a Standardized Extract from Myracrodruon urundeuva Fr. All. (Aroeira-Do-Sertão), as Evaluated by a Parkinson’s Disease Model in Rats. Parkinson’s Disease 2014;2014. https://doi.org/10.1155/2014/519615.
  • [28] Kiasalari Z, Khalili M, Baluchnejadmojarad T, Roghani M. Protective Effect of Oral Hesperetin Against Unilateral Striatal 6-Hydroxydopamine Damage in the Rat. Neurochemical Research 2015;41:1065–72. https://doi.org/10.1007/S11064-015-1796-6.
  • [29] Mcgeer PL, Itagaki S, Boyes BE, Mcgeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson ’ s and Alzheimer ’ s disease brains 1988.
  • [30] Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 1996;47. https://doi.org/10.1212/WNL.47.6_SUPPL_3.161S.
  • [31] Serra JA, Domínguez RO, de Lustig ES, Guareschi EM, Famulari AL, Bartolomé EL, et al. Parkinson’s disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson’s, Alzheimer’s and vascular dementia patients. Journal of Neural Transmission (Vienna, Austria : 1996) 2001;108:1135–48. https://doi.org/10.1007/S007020170003.
  • [32] Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, et al. Cellular/Molecular Mechanism of Toxicity in Rotenone Models of Parkinson’s Disease. 2003.
  • [33] Piper MDW, Skorupa D, Partridge L. Diet, metabolism and lifespan in Drosophila. Experimental Gerontology 2005;40:857–62. https://doi.org/10.1016/J.EXGER.2005.06.013.
  • [34] McGuire SE, Deshazer M, Davis RL. Thirty years of olfactory learning and memory research in Drosophila melanogaster. Progress in Neurobiology 2005;76:328–47. https://doi.org/10.1016/J.PNEUROBIO.2005.09.003.
  • [35] Wang HL, Sun ZO, Rehman RU, Wang H, Wang YF, Wang H. Rosemary Extract-Mediated Lifespan Extension and Attenuated Oxidative Damage in Drosophila melanogaster Fed on High-Fat Diet. Journal of Food Science 2017;82:1006–11. https://doi.org/10.1111/1750-3841.13656.
  • [36] Skorupa DA, Dervisefendic A, Zwiener J, Pletcher SD. Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell 2008;7:478–90. https://doi.org/10.1111/J.1474-9726.2008.00400.X.

Neuroprotective Effect of farnesol Against Rotenone Induced Parkinson’s Disease in Drosophila Melanogaster

Year 2023, Volume: 43 Issue: 1, 15 - 21, 01.03.2023

Jayaram Saravanan Praveen Thaggikuppe Krishnamurthy

https://doi.org/10.52794/hujpharm.1080352

Abstract

The current study aimed to investigate the neuroprotective effects of farnesol on rotenone-induced neurotoxicity in Drosophila melanogaster. Neurotoxicity was induced in Drosophila melanogaster by administering 500 μmol of rotenone and then the flies were administered either 300 μmol or 600 μmol of farnesol in the diet for the duration of the experiment. The study measured the effect of farnesol on longevity through a survival rate study, and locomotor function through a negative geotaxis assay. In addition, the study also estimated in vivo antioxidant parameters to determine the impact of farnesol on oxidative stress. The results showed that farnesol improved both longevity and locomotor function in the flies treated with 300 μmol or 600 μmol of test compound compared to control. The antioxidant studies also demonstrated that farnesol enhanced the catalase and superoxide dismutase activity and decreased lipid peroxidation. Based on these findings, it is concluded that farnesol might exhibit a significant neuroprotective effect against Parkinson’s disease.

Keywords

Farnesol Drosophila melanogaster negative geotaxis survival rate antioxidants

References

  • [1] Jankovic J. Parkinson’s disease: Clinical features and diagnosis. Journal of Neurology, Neurosurgery and Psychiatry 2008;79:368–76. https://doi.org/10.1136/jnnp.2007.131045.
  • [2] Guo JD, Zhao X, Li Y, Li GR, Liu XL. Damage to dopaminergic neurons by oxidative stress in Parkinson’s disease (Review). International Journal of Molecular Medicine 2018;41:1817–25. https://doi.org/10.3892/ijmm.2018.3406.
  • [3] Chen C, Turnbull DM, Reeve AK. Mitochondrial dysfunction in Parkinson’s disease—cause or consequence? Biology 2019;8:1–26. https://doi.org/10.3390/biology8020038.
  • [4] Ebrahimi-Fakhari D, Wahlster L, McLean PJ. Protein degradation pathways in Parkinson’s disease: Curse or blessing. Acta Neuropathologica 2012;124:153–72. https://doi.org/10.1007/s00401-012-1004-6.
  • [5] Zaichick S v., McGrath KM, Caraveo G. The role of Ca2+ signaling in Parkinson’s disease. DMM Disease Models and Mechanisms 2017;10:519–35. https://doi.org/10.1242/dmm.028738.
  • [6] Wang T, Zhang W, Pei Z, Block M, Wilson B, Reece JM, et al. Reactive microgliosis participates in MPP + ‐induced dopaminergic neurodegeneration: role of 67 kDa laminin receptor . The FASEB Journal 2006;20:906–15. https://doi.org/10.1096/fj.05-5053com.
  • [7] Hwang O. Role of Oxidative Stress in Parkinson’s Disease. Experimental Neurobiology 2013;22:11–7. https://doi.org/10.5607/en.2013.22.1.11.
  • [8] Cacabelos R. Parkinson’s disease: From pathogenesis to pharmacogenomics. International Journal of Molecular Sciences 2017;18. https://doi.org/10.3390/ijms18030551.
  • [9] Puspita L, Chung SY, Shim JW. Oxidative stress and cellular pathologies in Parkinson’s disease. Molecular Brain 2017;10. https://doi.org/10.1186/s13041-017-0340-9.
  • [10] Lisha J, Saravanana J, Santilna KS, Praveen TK, Rajkumar P, Wadhwani AD, et al. Neuroprotective activity of farnesol against bilateral common carotid artery occlusion induced cerebral ischemia/reperfusion injury in mice. Latin American Journal of Pharmacy 2019;38:572–8.
  • [11] Jung YY, Hwang ST, Sethi G, Fan L, Arfuso F, Ahn KS. Potential anti-inflammatory and anti-cancer properties of farnesol. Molecules 2018;23:1–15. https://doi.org/10.3390/molecules23112827.
  • [12] Qamar W, Sultana S. Farnesol ameliorates massive inflammation, oxidative stress and lung injury induced by intratracheal instillation of cigarette smoke extract in rats: An initial step in lung chemoprevention. Chemico-Biological Interactions 2008;176:79–87. https://doi.org/10.1016/j.cbi.2008.08.011.
  • [13] Burke YD, Stark MJ, Roach SL, Sen SE, Crowell PL. Inhibition of pancreatic cancer growth by the dietary isoprenoids farnesol and geraniol. Lipids 1997;32:151–6. https://doi.org/10.1007/s11745-997-0019-y.
  • [14] Jahangir T, Khan TH, Prasad L, Sultana S. Farnesol prevents Fe-NTA-mediated renal oxidative stress and early tumour promotion markers in rats. Human and Experimental Toxicology 2006;25:235–42. https://doi.org/10.1191/0960327106ht616oa.
  • [15] Hirth F. Drosophila melanogaster in the Study of Human Neurodegeneration. CNS & Neurological Disorders Drug Targets 2010;9:504. https://doi.org/10.2174/187152710791556104.
  • [16] Coulom H, Birman S. Chronic exposure to rotenone models sporadic Parkinson’s disease in Drosophila melanogaster. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 2004;24:10993–8. https://doi.org/10.1523/JNEUROSCI.2993-04.2004.
  • [17] Ambegaokar SS, Roy B, Jackson GR. Neurodegenerative models in Drosophila: polyglutamine disorders, Parkinson disease, and amyotrophic lateral sclerosis. Neurobiology of Disease 2010;40:29–39. https://doi.org/10.1016/J.NBD.2010.05.026.
  • [18] Lakkappa N, Krishnamurthy PT, Pandareesh MD, Hammock BD, Hwang SH. Soluble epoxide hydrolase inhibitor, APAU, protects dopaminergic neurons against rotenone induced neurotoxicity: Implications for Parkinson’s disease. NeuroToxicology 2019;70:135–45. https://doi.org/10.1016/j.neuro.2018.11.010.
  • [19] Hosamani R, Ramesh SR, Muralidhara. Attenuation of rotenone-induced mitochondrial oxidative damage and neurotoxicty in drosophila melanogaster supplemented with creatine. Neurochemical Research 2010;35:1402–12. https://doi.org/10.1007/s11064-010-0198-z.
  • [20] Wongchum N, Dechakhamphu A. Ethanol extract of Cassia siamea L. increases life span in Drosophila melanogaster. Biochemistry and Biophysics Reports 2021;25. https://doi.org/10.1016/j.bbrep.2021.100925.
  • [21] Hosamani R, Muralidhara. Neuroprotective efficacy of Bacopa monnieri against rotenone induced oxidative stress and neurotoxicity in Drosophila melanogaster. NeuroToxicology 2009;30:977–85. https://doi.org/10.1016/j.neuro.2009.08.012.
  • [22] Ohkawa H, Ohishi N, Yagi K. Reaction of linoleic acid hydroperoxide with thiobarbituric acid. Undefined 1978.
  • [23] Masuoka N, Wakimoto M, Ubuka T, Nakano T. Spectrophotometric determination of hydrogen peroxide: Catalase activity and rates of hydrogen peroxide removal by erythrocytes. Clinica Chimica Acta 1996;254:101–12. https://doi.org/10.1016/0009-8981(96)06374-7.
  • [24] MARKLUND S, MARKLUND G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry 1974;47:469–74. https://doi.org/10.1111/J.1432-1033.1974.TB03714.X.
  • [25] Smith GA, Heuer A, Dunnett SB, Lane EL. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: predicting l-DOPA-induced dyskinesia. Behavioural Brain Research 2012;226:281–92. https://doi.org/10.1016/J.BBR.2011.09.025.
  • [26] Bargiotas P, Konitsiotis S. Levodopa-induced dyskinesias in Parkinson’s disease: emerging treatments. Neuropsychiatric Disease and Treatment 2013;9:1605. https://doi.org/10.2147/NDT.S36693.
  • [27] Calou I, Bandeira MA, Aguiar-Galvão W, Cerqueira G, Siqueira R, Neves KR, et al. Neuroprotective Properties of a Standardized Extract from Myracrodruon urundeuva Fr. All. (Aroeira-Do-Sertão), as Evaluated by a Parkinson’s Disease Model in Rats. Parkinson’s Disease 2014;2014. https://doi.org/10.1155/2014/519615.
  • [28] Kiasalari Z, Khalili M, Baluchnejadmojarad T, Roghani M. Protective Effect of Oral Hesperetin Against Unilateral Striatal 6-Hydroxydopamine Damage in the Rat. Neurochemical Research 2015;41:1065–72. https://doi.org/10.1007/S11064-015-1796-6.
  • [29] Mcgeer PL, Itagaki S, Boyes BE, Mcgeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson ’ s and Alzheimer ’ s disease brains 1988.
  • [30] Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 1996;47. https://doi.org/10.1212/WNL.47.6_SUPPL_3.161S.
  • [31] Serra JA, Domínguez RO, de Lustig ES, Guareschi EM, Famulari AL, Bartolomé EL, et al. Parkinson’s disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson’s, Alzheimer’s and vascular dementia patients. Journal of Neural Transmission (Vienna, Austria : 1996) 2001;108:1135–48. https://doi.org/10.1007/S007020170003.
  • [32] Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, et al. Cellular/Molecular Mechanism of Toxicity in Rotenone Models of Parkinson’s Disease. 2003.
  • [33] Piper MDW, Skorupa D, Partridge L. Diet, metabolism and lifespan in Drosophila. Experimental Gerontology 2005;40:857–62. https://doi.org/10.1016/J.EXGER.2005.06.013.
  • [34] McGuire SE, Deshazer M, Davis RL. Thirty years of olfactory learning and memory research in Drosophila melanogaster. Progress in Neurobiology 2005;76:328–47. https://doi.org/10.1016/J.PNEUROBIO.2005.09.003.
  • [35] Wang HL, Sun ZO, Rehman RU, Wang H, Wang YF, Wang H. Rosemary Extract-Mediated Lifespan Extension and Attenuated Oxidative Damage in Drosophila melanogaster Fed on High-Fat Diet. Journal of Food Science 2017;82:1006–11. https://doi.org/10.1111/1750-3841.13656.
  • [36] Skorupa DA, Dervisefendic A, Zwiener J, Pletcher SD. Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell 2008;7:478–90. https://doi.org/10.1111/J.1474-9726.2008.00400.X.
There are 36 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Research Articles
Authors

Jayaram Saravanan This is me 0000-0001-9307-2692

Praveen Thaggikuppe Krishnamurthy

Publication Date March 1, 2023
Acceptance Date June 10, 2022
Published in Issue Year 2023 Volume: 43 Issue: 1

Cite

Vancouver Saravanan J, Krishnamurthy PT. Neuroprotective Effect of Farnesol Against Rotenone Induced Parkinson’s Disease in Drosophila Melanogaster. HUJPHARM. 2023;43(1):15-21.