Baphia macrocalyx Leaf Extract Attenuates Rotenone-induced Toxicity in Drosophila melanogaster Model of Parkinson’s Disease
Corresponding Author(s) : Flora Stephano
Journal of Humanities & Social Science (JHSS),
Vol. 10 No. 1 (2021)
Abstract
Parkinson’s disease (PD) is a motor disorder mostly affecting aged people, with not known
standard therapy. The use of natural products is increasingly gaining attention for the
treatment of different diseases. Baphia macrocalyx is a plant previously associated with
antioxidant activities in in vitro studies. Thus, the aim of this study was to evaluate the
ameliorative potential of methanolic leaf extract of Baphia macrocalyx (MEBM) on
rotenone-triggered toxicity in Drosophila melanogaster. To this end, the study used a
neurotoxin, rotenone, to induce PD in the fruit-fly to create a chemical PD in vivo model.
Using biochemical, behavioural and molecular analyses, this study revealed that B.
macrocalyx rescued motor disability in PD-induced flies. Mechanistically, B. macrocalyx
suppressed the oxidative stress, and lipid peroxidation increases generated by rotenone.
In addition, expression levels of mRNA of antioxidant enzymes; superoxide dismutase and
catalase were elevated in flies treated with rotenone, and normalized in flies that were cotreated with MEBM. Conclusively, the ability of B. macrocalyx of ameliorating rotenone
induced oxidative stress and PD-like locomotor deficits in D. melanogaster verify its
antioxidant properties.
Keywords
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX
- Abolaji, A.O., A.O. Adedara, M.A. Adie, M. Vicente-Crespo & E.O. Farombi. 2018. Resveratrol
- Prolongs Lifespan and Improves 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced
- Oxidative Damage and Behavioural Deficits in Drosophila Melanogaster. Biochem Biophys Res
- Commun 503: 1042–1048. https: //doi.org/10.1016/j.bbrc.2018.06.114.
- Adeyemi, O.O., O.K. Yemitan & A.E. Taiwo. 2006. Neurosedative and Muscle-Relaxant Activities of
- Ethyl Acetate Extract of Baphia Nitida AFZEL. J of Ethnopharmacol 106: 312–316. doi: 10.1016/
- j.jep.2005.11.035.
- Bwire, N.R. 2015. Phytochemical and Bioactivity Studies on the Constituents of Baphia Macrocalyx
- Afzel, Baphia Keniensis Afzel, Syzigium Cordatum Hochst and Pavetta Teitana K. Schum. PhD thesis,
- University of Dar es Salaam.
- Coulom, H. & S. Birman. 2004. Chronic Exposure to Rotenone Models Sporadic Parkinson’s Disease
- in Drosophila Melanogaster. J Neurosc 24: 10993–8. http: //doi: 10.1523/jneurosci.2993-04.2004.
- De Andrade Teles, R.B., T.C. Diniz, T.C. Costa Pinto, R.G. De Oliveira Júnior, E. Gama, M. Silva, … &
- J.R.G. Da Silva Almeida. 2018. Flavonoids As Therapeutic Agents in Alzheimer’s and Parkinson’s
- Diseases: A Systematic Review of Preclinical Evidences. Oxid Med Cell Longev. https: //doi:
- 1155/2018/7043213.
- Eze, V.C., M.I. Ezeja, S.O. Oneja & O.I. Obi. 2015. Antibactrial, Phytochemical and Antioxidant
- Properties of the Leaf and Root Bark Extract of Baphia Nitida and Bacteria Associated With
- Wound and Enteric Infections. World Journal of Pharmacetical Research, 4(3): 1111-1122.
- Farombi, E.O., A.O. Abolaji, T.H. Farombi, A.S. Oropo, O.A. Owoje & M.T. Awunah. 2018. Garcinia
- Kola Seed Biflavonoid Fraction (Kolaviron), Increases Longevity and Attenuates RotenoneInduced Toxicity in Drosophila Melanogaste.r Pestic Biochem Phys 145: 39–45. https: //doi.org/
- 1016/ j.pestbp.2018.01.002.
- Fatima, A., R. Rahul, S. Jyoti, F. Naz, F. Ali & Y.H. Siddique. 2017. Protective Effect of Tangeritin in
- Transgenic Drosophila Model of Parkinson’s Disease. Front Biosc, 9: 44–53. http: //doi:
- 2741/e784.
- Feany, M.B. & W.W. Bender. 2000. A Drosophila Model of Parkinson’s Disease. Nature, 404: 394–398.
- Forno, L. 1996. Neuropathology of Parkinsons Disease. Neuropathol Exp Neurol, 55: 259–272.
- Gupta, A., V.L. Dawson & T.M. Dawson. 2008. What Causes Cell Death in Parkinson’s Disease? Ann
- Neurol, http: // doi: 10.1002/ana.21573.
- Hirsch, L., N. Jette, A. Frolkis, T. Steeves & T. Pringsheim. 2016. The Incidence of Parkinson’s
- Disease: A Systematic Review and Meta-Analysis. Neuroepidemiology, 46: 292–300. http: //doi:
- 1159/000445751.
- Hwang, O. 2013. Role of Oxidative Stress in Parkinson’s Disease. Exp Neurobiol, 22: 11. http: //doi:
- 5607/en.2013.22.1.11.
- Kapingu, M.C., J.J. Magadula, Z.H. Mbwambo, D.A. Mulholland. 2008 Puguflavanones A and B;
- Prenylated Flavanones from Baphia Puguensis. Nat Prod Comm, 3: 749-753.
- Keroletswe, N., R.R.T. Majinda & I.B. Masesane. 2018. A New 3-Prenyl-2-Flavene and Other
- Extractives from Baphia Massaiensis and Their Antimicrobial Activities. Nat Prod Commun. 13:
- –438. http: //doi: 10.1177/1934578x1801300414.
- Klingelhoefer, L. & H. Reichmann. 2015. Pathogenesis of Parkinson Disease—The Gut–Brain Axis
- and Environmental Factors. Nat Rev Neurol, 11: 625–636. http: // doi: 10.1038/nrneurol.2015.197.
- Livak, K.J. & T.D. Schmittgen. 2001. Analysis of Relative Gene Expression Data Using Real-Time
- Quantitative PCR and the 2-??CT Method. Methods, 25: 402–408. http: //doi: 10.1006/ meth. 2001.
- Malekela, R.S., J.J. Mwakalinga, R.M. Antony, F. Stephano. 2020. Anti-Diarrhoeal, Anti-Oxidative Stress
- and Acute Toxicity of Methanolic Leaf Extract of Baphia Macrocalyx in Mice. Tanz J Sci., 46: 216-227.
- Meenalochani, S. 2016. Mechanisms for Neuronal Cell Death in Parkinson’s Disease: Pathological
- Cross Talks Between Epigenetics and Various Signalling Pathways. In S.T. Dheen (Ed.). Rijeka:
- Intechopen. Ch. 3. doi: 10.5772/63103.
- Miller, R.L., M. James-Kracje, G.Y. Sun & A.Y. Sum. 2009. Oxidative and Inflammatory Pathways in
- Parkinson’s Disease. Neurochem Res, 34: 55–65. http: // doi: 10.1007/s11064-008-9656-2.
- Nagoshi, E. 2018. Drosophila Models of Sporadic Parkinson’s Disease. Int J Mol Sci. http: //doi:
- 3390/ijms19113343.
- Nisticò, R., B. Mehdawy, S. Piccirilli & N. Mercuri. 2011. Paraquat- and Rotenone-Induced Models
- of Parkinson’s Disease. Inter J Immunopathol Pharmacol 24: 313–22. http: //doi:
- 1177/039463201102400205.
- Nkunya, M.H.H. 2005. Unusual Metabolites from Some Tanzanian Indigenous Plant Species. Pure
- Appl Chem, 77: 1943–1955. http: //doi: 10.1351/pac200577111943.
- Ogunwa, T.H. 2016. Comparative Qualitative Analysis of Phytochemicals in Baphia Pubescens and
- Clerodendrum Volubile Leaves. Asian J. Ethnopharmacol. Med. Foods 02: 18-21.
- Onyekwere, B.C., J.O. Echeme & R.I. Uchegbu. 2014. Isolation and Characterization of Baphianoside
- from the Leaves of Baphia Nitida. J Nat Sci Res. 4: 138-143.
- Puspita, L., S.Y. Chung, J. Shim. 2017. Oxidative Stress and Cellular Pathologies in Parkinson’s
- Disease, Mol Brain 10: 53. http: //doi: 10.1186/s13041-017-0340-9.
- Seidl, S.E., J.A. Potashkin. 2011. The Promise of Neuroprotective Agents in Parkinson’s Disease.
- Front Neurol 1–19. http: //doi: 10.3389/fneur.2011.00068.
- Sherer, T.B., R. Betarbet, C.M. Testa,, B.B. Seo, J.R. Richardson, J.H. Kim & J.T. Greenamyre. 2003.
- Mechanism of Toxicity in Rotenone Models of Parkinson’s Disease. J Neurosc 23: 10756–10764.
- http: //doi: 10.1523/jneurosci.23-34-10756.2003.
- Siddique, Y.H. M. Faisal,, F. Naz, S. Jyoti & Rahul. 2014. Role of Ocimum Sanctum Leaf Extract on
- Dietary Supplementation in the Transgenic Drosophila Model of Parkinson’s Disease. Chin J Nat
- Medicines 12: 777–781. https: //doi.org/10.1016/s1875-5364(14)60118-7.
- Siddique, Y.H., S. Jyoti, F. Naz & M. Afzal. 2012. Validation of 1-Methyl-2-Phenylindole Method for
- Estimating Lipid Peroxidation in the Third Instar Larvae of Transgenic Drosophila Melanogaster
- (Hsp70-Lacz)Bg (9). Pharm Methods 3: 94–7. http: //doi: 10.4103/2229-4708.103883.
- Siddique, Y.H., S. Jyoti, F. Naz & Rahul. 2018. Protective Effect of Luteolin on the Transgenic
- Drosophila Model of Parkinson’s Disease. Braz J Pharm Sci. http: //doi: 10.1590/s2175-
- Siima, A.A., F. Stephano, J.J.E. Munissi, , S.S. Nyandoro. 2020. Ameliorative Effects of Flavonoids and
- Polyketides on the Rotenone Induced Drosophila Model of Parkinson's Disease..
- Stephano, F., S Nolte., J. Hoffmann, S. El-Kholy, J. Von Frieling, I. Bruchhaus, C. Fink & T. Roeder.
- Impaired Wnt Signaling in Dopamine Containing Neurons Is Associated With
- Pathogenesis in a Rotenone Triggered Drosophila Parkinson’s Disease Model. Sci Rep 8: 2372.
- http: //doi: 10.1038/s41598-018-20836-w.
- Sudati, J.H., F.A. Vieira, S.S. Pavin, G.R.M. Dias, R.L. Seeger, R. Golombieski & N.V. Barbosa 2013.
- Valeriana Officinalis Attenuates the Rotenone-Induced Toxicity in Drosophila Melanogaster
- Neurotoxicology, 37: 118–126. https: //doi.org/10.1016/j.neuro.2013.04.006.
- Uversky, V.N. 2004. Neurotoxicant-Induced Animal Models of Parkinson’s Disease: Understanding
- the Role of Rotenone, Maneb and Paraquat in Neurodegeneration. Cell Tissue Res, 318: 225–241.
- http: //doi: 10.1007/s00441-004-0937-z.
- Wei, Z, Li X, Li Xi, Liu Q & Y. Cheng 2018. Oxidative Stress in Parkinson’s Disease: A Systematic
- Review and Meta-Analysis. Front Mol Neurosci. https: //doi.org/article/ 10.3389/
- fnmol.2018.00236.
- Whitworth, A.J. 2011. Drosophila Models of Parkinson’s Disease. Adv Genet, 73: 1–50. http: //doi:
- 1016/b978-0-12-380860-8.00001-x.
- Yang, C., T. Zhang, W. Wang, Y. Xiang, Q. Huang, C. Xie, … & H. Gao. 2020. Brain-Region Specific
- Metabolic Abnormalities in Parkinson’s Disease and Levodopa-Induced Dyskinesia. Front in
- Aging Neurosci 12: 75. http: //doi: 10.3389/fnagi.2020.00075.
- Yao-Kouassi, P. A., A. A. Magid, B. Richard, A. Martinez, M. J. Jacquier, C. Caron, & M. Zeches-Hanrot.
- Isoflavonoid Glycosides from the Roots of Baphia Bancoensis. J. Nat. Prod. 71(12): 2073-2076.
References
Abolaji, A.O., A.O. Adedara, M.A. Adie, M. Vicente-Crespo & E.O. Farombi. 2018. Resveratrol
Prolongs Lifespan and Improves 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced
Oxidative Damage and Behavioural Deficits in Drosophila Melanogaster. Biochem Biophys Res
Commun 503: 1042–1048. https: //doi.org/10.1016/j.bbrc.2018.06.114.
Adeyemi, O.O., O.K. Yemitan & A.E. Taiwo. 2006. Neurosedative and Muscle-Relaxant Activities of
Ethyl Acetate Extract of Baphia Nitida AFZEL. J of Ethnopharmacol 106: 312–316. doi: 10.1016/
j.jep.2005.11.035.
Bwire, N.R. 2015. Phytochemical and Bioactivity Studies on the Constituents of Baphia Macrocalyx
Afzel, Baphia Keniensis Afzel, Syzigium Cordatum Hochst and Pavetta Teitana K. Schum. PhD thesis,
University of Dar es Salaam.
Coulom, H. & S. Birman. 2004. Chronic Exposure to Rotenone Models Sporadic Parkinson’s Disease
in Drosophila Melanogaster. J Neurosc 24: 10993–8. http: //doi: 10.1523/jneurosci.2993-04.2004.
De Andrade Teles, R.B., T.C. Diniz, T.C. Costa Pinto, R.G. De Oliveira Júnior, E. Gama, M. Silva, … &
J.R.G. Da Silva Almeida. 2018. Flavonoids As Therapeutic Agents in Alzheimer’s and Parkinson’s
Diseases: A Systematic Review of Preclinical Evidences. Oxid Med Cell Longev. https: //doi:
1155/2018/7043213.
Eze, V.C., M.I. Ezeja, S.O. Oneja & O.I. Obi. 2015. Antibactrial, Phytochemical and Antioxidant
Properties of the Leaf and Root Bark Extract of Baphia Nitida and Bacteria Associated With
Wound and Enteric Infections. World Journal of Pharmacetical Research, 4(3): 1111-1122.
Farombi, E.O., A.O. Abolaji, T.H. Farombi, A.S. Oropo, O.A. Owoje & M.T. Awunah. 2018. Garcinia
Kola Seed Biflavonoid Fraction (Kolaviron), Increases Longevity and Attenuates RotenoneInduced Toxicity in Drosophila Melanogaste.r Pestic Biochem Phys 145: 39–45. https: //doi.org/
1016/ j.pestbp.2018.01.002.
Fatima, A., R. Rahul, S. Jyoti, F. Naz, F. Ali & Y.H. Siddique. 2017. Protective Effect of Tangeritin in
Transgenic Drosophila Model of Parkinson’s Disease. Front Biosc, 9: 44–53. http: //doi:
2741/e784.
Feany, M.B. & W.W. Bender. 2000. A Drosophila Model of Parkinson’s Disease. Nature, 404: 394–398.
Forno, L. 1996. Neuropathology of Parkinsons Disease. Neuropathol Exp Neurol, 55: 259–272.
Gupta, A., V.L. Dawson & T.M. Dawson. 2008. What Causes Cell Death in Parkinson’s Disease? Ann
Neurol, http: // doi: 10.1002/ana.21573.
Hirsch, L., N. Jette, A. Frolkis, T. Steeves & T. Pringsheim. 2016. The Incidence of Parkinson’s
Disease: A Systematic Review and Meta-Analysis. Neuroepidemiology, 46: 292–300. http: //doi:
1159/000445751.
Hwang, O. 2013. Role of Oxidative Stress in Parkinson’s Disease. Exp Neurobiol, 22: 11. http: //doi:
5607/en.2013.22.1.11.
Kapingu, M.C., J.J. Magadula, Z.H. Mbwambo, D.A. Mulholland. 2008 Puguflavanones A and B;
Prenylated Flavanones from Baphia Puguensis. Nat Prod Comm, 3: 749-753.
Keroletswe, N., R.R.T. Majinda & I.B. Masesane. 2018. A New 3-Prenyl-2-Flavene and Other
Extractives from Baphia Massaiensis and Their Antimicrobial Activities. Nat Prod Commun. 13:
–438. http: //doi: 10.1177/1934578x1801300414.
Klingelhoefer, L. & H. Reichmann. 2015. Pathogenesis of Parkinson Disease—The Gut–Brain Axis
and Environmental Factors. Nat Rev Neurol, 11: 625–636. http: // doi: 10.1038/nrneurol.2015.197.
Livak, K.J. & T.D. Schmittgen. 2001. Analysis of Relative Gene Expression Data Using Real-Time
Quantitative PCR and the 2-??CT Method. Methods, 25: 402–408. http: //doi: 10.1006/ meth. 2001.
Malekela, R.S., J.J. Mwakalinga, R.M. Antony, F. Stephano. 2020. Anti-Diarrhoeal, Anti-Oxidative Stress
and Acute Toxicity of Methanolic Leaf Extract of Baphia Macrocalyx in Mice. Tanz J Sci., 46: 216-227.
Meenalochani, S. 2016. Mechanisms for Neuronal Cell Death in Parkinson’s Disease: Pathological
Cross Talks Between Epigenetics and Various Signalling Pathways. In S.T. Dheen (Ed.). Rijeka:
Intechopen. Ch. 3. doi: 10.5772/63103.
Miller, R.L., M. James-Kracje, G.Y. Sun & A.Y. Sum. 2009. Oxidative and Inflammatory Pathways in
Parkinson’s Disease. Neurochem Res, 34: 55–65. http: // doi: 10.1007/s11064-008-9656-2.
Nagoshi, E. 2018. Drosophila Models of Sporadic Parkinson’s Disease. Int J Mol Sci. http: //doi:
3390/ijms19113343.
Nisticò, R., B. Mehdawy, S. Piccirilli & N. Mercuri. 2011. Paraquat- and Rotenone-Induced Models
of Parkinson’s Disease. Inter J Immunopathol Pharmacol 24: 313–22. http: //doi:
1177/039463201102400205.
Nkunya, M.H.H. 2005. Unusual Metabolites from Some Tanzanian Indigenous Plant Species. Pure
Appl Chem, 77: 1943–1955. http: //doi: 10.1351/pac200577111943.
Ogunwa, T.H. 2016. Comparative Qualitative Analysis of Phytochemicals in Baphia Pubescens and
Clerodendrum Volubile Leaves. Asian J. Ethnopharmacol. Med. Foods 02: 18-21.
Onyekwere, B.C., J.O. Echeme & R.I. Uchegbu. 2014. Isolation and Characterization of Baphianoside
from the Leaves of Baphia Nitida. J Nat Sci Res. 4: 138-143.
Puspita, L., S.Y. Chung, J. Shim. 2017. Oxidative Stress and Cellular Pathologies in Parkinson’s
Disease, Mol Brain 10: 53. http: //doi: 10.1186/s13041-017-0340-9.
Seidl, S.E., J.A. Potashkin. 2011. The Promise of Neuroprotective Agents in Parkinson’s Disease.
Front Neurol 1–19. http: //doi: 10.3389/fneur.2011.00068.
Sherer, T.B., R. Betarbet, C.M. Testa,, B.B. Seo, J.R. Richardson, J.H. Kim & J.T. Greenamyre. 2003.
Mechanism of Toxicity in Rotenone Models of Parkinson’s Disease. J Neurosc 23: 10756–10764.
http: //doi: 10.1523/jneurosci.23-34-10756.2003.
Siddique, Y.H. M. Faisal,, F. Naz, S. Jyoti & Rahul. 2014. Role of Ocimum Sanctum Leaf Extract on
Dietary Supplementation in the Transgenic Drosophila Model of Parkinson’s Disease. Chin J Nat
Medicines 12: 777–781. https: //doi.org/10.1016/s1875-5364(14)60118-7.
Siddique, Y.H., S. Jyoti, F. Naz & M. Afzal. 2012. Validation of 1-Methyl-2-Phenylindole Method for
Estimating Lipid Peroxidation in the Third Instar Larvae of Transgenic Drosophila Melanogaster
(Hsp70-Lacz)Bg (9). Pharm Methods 3: 94–7. http: //doi: 10.4103/2229-4708.103883.
Siddique, Y.H., S. Jyoti, F. Naz & Rahul. 2018. Protective Effect of Luteolin on the Transgenic
Drosophila Model of Parkinson’s Disease. Braz J Pharm Sci. http: //doi: 10.1590/s2175-
Siima, A.A., F. Stephano, J.J.E. Munissi, , S.S. Nyandoro. 2020. Ameliorative Effects of Flavonoids and
Polyketides on the Rotenone Induced Drosophila Model of Parkinson's Disease..
Stephano, F., S Nolte., J. Hoffmann, S. El-Kholy, J. Von Frieling, I. Bruchhaus, C. Fink & T. Roeder.
Impaired Wnt Signaling in Dopamine Containing Neurons Is Associated With
Pathogenesis in a Rotenone Triggered Drosophila Parkinson’s Disease Model. Sci Rep 8: 2372.
http: //doi: 10.1038/s41598-018-20836-w.
Sudati, J.H., F.A. Vieira, S.S. Pavin, G.R.M. Dias, R.L. Seeger, R. Golombieski & N.V. Barbosa 2013.
Valeriana Officinalis Attenuates the Rotenone-Induced Toxicity in Drosophila Melanogaster
Neurotoxicology, 37: 118–126. https: //doi.org/10.1016/j.neuro.2013.04.006.
Uversky, V.N. 2004. Neurotoxicant-Induced Animal Models of Parkinson’s Disease: Understanding
the Role of Rotenone, Maneb and Paraquat in Neurodegeneration. Cell Tissue Res, 318: 225–241.
http: //doi: 10.1007/s00441-004-0937-z.
Wei, Z, Li X, Li Xi, Liu Q & Y. Cheng 2018. Oxidative Stress in Parkinson’s Disease: A Systematic
Review and Meta-Analysis. Front Mol Neurosci. https: //doi.org/article/ 10.3389/
fnmol.2018.00236.
Whitworth, A.J. 2011. Drosophila Models of Parkinson’s Disease. Adv Genet, 73: 1–50. http: //doi:
1016/b978-0-12-380860-8.00001-x.
Yang, C., T. Zhang, W. Wang, Y. Xiang, Q. Huang, C. Xie, … & H. Gao. 2020. Brain-Region Specific
Metabolic Abnormalities in Parkinson’s Disease and Levodopa-Induced Dyskinesia. Front in
Aging Neurosci 12: 75. http: //doi: 10.3389/fnagi.2020.00075.
Yao-Kouassi, P. A., A. A. Magid, B. Richard, A. Martinez, M. J. Jacquier, C. Caron, & M. Zeches-Hanrot.
Isoflavonoid Glycosides from the Roots of Baphia Bancoensis. J. Nat. Prod. 71(12): 2073-2076.