The Beneficial Effect of Rice Bran Extract Against Rotenone-Induced Experimental Parkinson’s Disease in Rats

Author(s): Sachin Kumar, Puneet Kumar*

Journal Name: Current Molecular Pharmacology

Volume 14 , Issue 3 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Neurodegenerative diseases have become an increasing cause of various disabilities worldwide, followed by aging, including Parkinson’s disease (PD). Parkinson’s disease is a degenerative brain disorder distinguished by growing motor & non-motor failure due to the degeneration of medium-sized spiked neurons in the striatum region. Rotenone is often employed to originate the animal model of PD. It is a powerful blocker of mitochondrial complex-I, mitochondrial electron transport chain that reliably produces Parkinsonism-like symptoms in rats. Rice bran (RB) is very rich in polyunsaturated fatty acids (PUFA) and nutritionally beneficial compounds, such as γ-oryzanol, tocopherols, and tocotrienols and sterols are believed to have favorable outcomes on oxidative stress & mitochondrial function.

Objective: The present study has been designed to explore RB extract’s effect against rotenone-induced neurotoxicity in rats.

Methods: In the present study, Rotenone (2 mg/kg, s.c) was administered systemically for 28 days. The hexane extract of RB was prepared using Soxhlation. Hexane extract (250 & 500 mg/kg) was administered per oral for 28 days in rotenone-treated groups. Behavioral parameters (grip strength, motor coordination, locomotion, and catalepsy) were conducted on the 7th, 14th, 21st, and 28th day. Animals were sacrificed on the 29th day for biochemical estimation in the striatum and cortex.

Results: This study demonstrates significant alteration in behavioral parameters, oxidative burden (increased lipid peroxidation, nitrite concentration, and decreased glutathione, catalase, SOD) in rotenone-treated animals. Administration of hexane extract of RB prevented the behavioral, biochemical alterations induced by rotenone. The current research has been sketched to inspect RB extract’s effect against rotenone-developed neurotoxicity in rats.

Conclusion: The findings support that PD is associated with impairments in motor activity. The results also suggest that the nutraceutical rice bran that contains γ-oryzanol, Vitamin-E, ferulic acid etc., may underlie the adjuvant susceptibility towards rotenone-induced PD in experimental rats.

Keywords: Basal ganglia, oxidative stress, Parkinson's disease, rotenone, rice bran, rats.

Ahmed, O.G.; Mahmoud, M.; Abdelhamid, A.A. Behavioral evaluation of rotenone model of Parkinson’s disease in male Wistar rats. Sohag. Med. J., 2020, 24(2), 8-14.
Ali, M.A.; Islam, M.A.; Hossen, J.; Ibrahim, M. Antioxidant efficacy of rice bran extract on stabilisation of ghee under accelerated oxidation condition. Int. Food Res. J., 2019, 26(5), 1437-1445.
Ambrogini, P.; Torquato, P.; Bartolini, D.; Albertini, M.C.; Lattanzi, D.; Di Palma, M.; Marinelli, R.; Betti, M.; Minelli, A.; Cuppini, R.; Galli, F. Excitotoxicity, neuroinflammation and oxidant stress as molecular bases of epileptogenesis and epilepsy-derived neurodegeneration: The role of vitamin E. Biochim. Biophys. Acta Mol. Basis Dis., 2019, 1865(6), 1098-1112.
[] [PMID: 30703511]
Araujo, S.M.; de Paula, M.T.; Poetini, M.R.; Meichtry, L.; Bortolotto, V.C.; Zarzecki, M.S.; Jesse, C.R.; Prigol, M. Effectiveness of γ-oryzanol in reducing neuromotor deficits, dopamine depletion and oxidative stress in a Drosophila melanogaster model of Parkinson’s disease induced by rotenone. Neurotoxicology, 2015, 51, 96-105.
[] [PMID: 26366809]
Behrman, A.; Cody, J.; Elandary, S.; Flom, P.; Chitnis, S. The effect of SPEAK OUT! and The LOUD crowd on dysarthria due to Parkinson’s disease. Am. J. Speech Lang. Pathol., 2020, 29(3), 1448-1465.
[] [PMID: 32421347]
Bexter, A.; Kampa, B.M. MazeMaster: An open-source Python-based software package for controlling virtual reality experiments. bioRxiv, 2020.
Bhutani, M.K.; Bishnoi, M.; Kulkarni, S.K. Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol. Biochem. Behav., 2009, 92(1), 39-43.
[] [PMID: 19000708]
Bodie, A.R.; Micciche, A.C.; Atungulu, G.G.; Rothrock, M.J.; Ricke, S.C. Current trends of rice milling byproducts for agricultural applications and alternative food production systems. Front. Sustain. Food Syst, 2019, 3, 1-13.
Brandão-Teles, C.; de Almeida, V.; Cassoli, J.S.; Martins-de-Souza, D. Biochemical Pathways Triggered by Antipsychotics in Human [corrected] Oligodendrocytes: Potential of Discovering New Treatment Targets. Front. Pharmacol., 2019, 10, 186.
[] [PMID: 30890939]
Chin, K-Y.; Tay, S.S. A review on the relationship between tocotrienol and Alzheimer Disease. Nutrients, 2018, 10(7), 881.
[] [PMID: 29987193]
Chompoopong, S.; Jarungjitaree, S.; Punbanlaem, T.; Rungruang, T.; Chongthammakun, S.; Kettawan, A.; Taechowisan, T. Neuroprotective effects of germinated brown rice in rotenone-induced Parkinson’s-like disease rats. Neuromolecular Med., 2016, 18(3), 334-346.
[] [PMID: 27430236]
Cieślak, M.; Wojtczak, A. Role of purinergic receptors in the Alzheimer’s disease. Purinergic Signal., 2018, 14(4), 331-344.
[] [PMID: 30362042]
Dai, J.; Sha, R.; Wang, Z.; Cui, Y.; Fang, S.; Mao, J. Edible plant Jiaosu: manufacturing, bioactive compounds, potential health benefits, and safety aspects. J. Sci. Food Agric., 2020, 100(15), 5313-5323.
[] [PMID: 32419188]
Dhurve, S.A. A clinical study on kampavata (Parkinson’s disease) and it’s management with kapikacchu and basti. Indian J. Appl. Res., 2019, 9(11), 2249-555X.
Di Meo, F.; Valentino, A.; Petillo, O.; Peluso, G.; Filosa, S.; Crispi, S. Bioactive Polyphenols and Neuromodulation: Molecular Mechanisms in Neurodegeneration. Int. J. Mol. Sci., 2020, 21(7), 2564.
[] [PMID: 32272735]
Ellman, G.L. Tissue sulfhydryl groups. Arch. Biochem. Biophys., 1959, 82(1), 70-77.
[] [PMID: 13650640]
Gan, J.; Sun, J.; Chang, X.; Li, W.; Li, J.; Niu, S.; Kong, L.; Zhang, T.; Wu, T.; Tang, M.; Xue, Y. Biodistribution and organ oxidative damage following 28 days oral administration of nanosilver with/without coating in mice. J. Appl. Toxicol., 2020, 40(6), 815-831.
[] [PMID: 31984544]
Gao, J.; Lai, M.Y.; Qin, W.X.; Yuan, Q.; Wu, Y.; Li, S.L.; Chen, J. [Acupuncture improves locomotor activity and learning-memory ability by improving hippocampal cellular autophagy in rats with fetal intrauterine distress]. Zhen Ci Yan Jiu, 2020, 45(4), 275-280.
[PMID: 32333531]
Garabadu, D.; Agrawal, N. Naringin exhibits neuroprotection against rotenone-induced neurotoxicity in experimental rodents. Neuromolecular Med., 2020, 22(2), 314-330.
[] [PMID: 31916219]
Geibl, F.F.; Henrich, M.T.; Oertel, W.H. Mesencephalic and extramesencephalic dopaminergic systems in Parkinson’s disease. J. Neural Transm. (Vienna), 2019, 126(4), 377-396.
[] [PMID: 30643975]
Gould, F.D.H.; Gross, A.; German, R.Z.; Richardson, J.R. Evidence of oropharyngeal dysfunction in feeding in the rat rotenone model of Parkinson’s Disease; Park Dis, 2018.
Green, L.C.; Wagner, D.A.; Glogowski, J.; Skipper, P.L.; Wishnok, J.S.; Tannenbaum, S.R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal. Biochem., 1982, 126(1), 131-138.
[] [PMID: 7181105]
Greene, J.G.; Noorian, A.R.; Srinivasan, S. Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson’s disease. Exp. Neurol., 2009, 218(1), 154-161.
[] [PMID: 19409896]
Hagl, S.; Kocher, A.; Schiborr, C.; Eckert, S.H.; Ciobanu, I.; Birringer, M.; El-Askary, H.; Helal, A.; Khayyal, M.T.; Frank, J.; Muller, W.E.; Eckert, G.P. Rice bran extract protects from mitochondrial dysfunction in guinea pig brains. Pharmacol. Res., 2013, 76, 17-27.
[] [PMID: 23827162]
Hagl, S.; Grewal, R.; Ciobanu, I.; Helal, A.; Khayyal, M.T.; Muller, W.E.; Eckert, G.P. Rice bran extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer’s disease. J. Alzheimers Dis., 2015, 43(3), 927-938.
[] [PMID: 25125472]
Hasan, W.; Rajak, R.; Kori, R.K.; Yadav, R.S.; Jat, D. Neuroprotective effects of mitochondria-targeted Quercetin against rotenone-induced oxidative damage in cerebellum of mice. Int. J. Nutr. Pharmacol. Neurol. Dis., 2019, 9(4), 136.
Heinz, S.; Freyberger, A.; Lawrenz, B.; Schladt, L.; Schmuck, G.; Ellinger-Ziegelbauer, H. Mechanistic investigations of the mitochondrial complex I inhibitor rotenone in the context of pharmacological and safety evaluation. Sci. Rep., 2017, 7, 45465.
[] [PMID: 28374803]
Huang, L.; Jiang, W.; Zhu, L.; Ma, C.; Ou, Z.; Luo, C.; Wu, J.; Wen, L.; Tan, Z.; Yi, J. γ-Oryzanol suppresses cell apoptosis by inhibiting reactive oxygen species-mediated mitochondrial signaling pathway in H2O2-stimulated L02 cells. Biomed. Pharmacother., 2020, 121, 109554.
[] [PMID: 31678753]
Jiang, T.; Sun, Q.; Chen, S. Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson’s disease and Alzheimer’s disease. Prog. Neurobiol., 2016, 147, 1-19.
[] [PMID: 27769868]
Johnson, M.E.; Stringer, A.; Bobrovskaya, L. Rotenone induces gastrointestinal pathology and microbiota alterations in a rat model of Parkinson’s disease. Neurotoxicology, 2018, 65, 174-185.
[] [PMID: 29471018]
Kaur, N.; Jamwal, S.; Deshmukh, R.; Gauttam, V.; Kumar, P. Beneficial effect of rice bran extract against 3-nitropropionic acid induced experimental Huntington’s disease in rats. Toxicol. Rep., 2015, 2, 1222-1232.
[] [PMID: 28962465]
Kavuri, S.; Sivanesan, S.; Rajagopalan, V. Oxidative stress and antioxidant status in rotenone induced rat models of Parkinson’s disease. Int. J. Res. Pharm. Sci., 2020, 11(1), 1-6.
Kono, Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch. Biochem. Biophys., 1978, 186(1), 189-195.
Lawana, V.; Cannon, J.R. Rotenone neurotoxicity: Relevance to Parkinson’s disease. Advances in Neurotoxicology; Elsevier, 2020, pp. 209-254.
Liu, Z.; Zhou, T.; Ziegler, A.C.; Dimitrion, P.; Zuo, L. Oxidative stress in neurodegenerative diseases: From molecular mechanisms to clinical applications. Oxid. Med. Cell. Longev., 2017, 2017, 2525967.
[] [PMID: 28785371]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[] [PMID: 14907713]
Luck, H. Methods of enzymatic analysis, 1st ed; Academic Press, 1963.
Mansour, R.M. Study of the possible protective effects of montelukast in rotenone induced-Parkinson’s disease model in rats; CU Theses, 2019.
Margabandhu, G.; Vanisree, A.J. Dopamine, a key factor of mitochondrial damage and neuronal toxicity on rotenone exposure and also parkinsonic motor dysfunction-Impact of asiaticoside with a probable vesicular involvement. J. Chem. Neuroanat., 2020, 106, 101788.
[] [PMID: 32278634]
Mehdi, B.J.; Tabassum, S.; Haider, S.; Perveen, T.; Nawaz, A.; Haleem, D.J. Nootropic and anti-stress effects of rice bran oil in male rats. J. Food Sci. Technol., 2015, 52(7), 4544-4550.
[] [PMID: 26139923]
Mehdi, B.J.; Haleem, D.J. Long-Term Administration of Rice Bran Oil Attenuates 5-HT1A receptor Dependent Responses in Rats. J. Anim. Res. Nutr., 2018, 3(1), 5.
Mostafa, A.O.; Abdel-Kader, R.M.; Heikal, O.A. Enhancement of cognitive functions by rice bran extract in a neuroinflammatory mouse model via regulation of PPARγ. J. Funct. Foods, 2018, 48, 314-321.
Nanda, N.B.P.; Das, P.C.; Jena, J. Use of rotenone as piscicide: toxicity levels in a few common freshwater predatory and weed fishes. J. Appl. Aquacult., 2009, 21(4), 241-249.
Ndayisaba, A.; Kaindlstorfer, C.; Wenning, G.K. Iron in neurodegeneration–cause or consequence? Front. Neurosci., 2019, 13, 180.
[] [PMID: 30881284]
Onukwufor, J.O.; Berry, B.J.; Wojtovich, A.P. Physiologic implications of reactive oxygen species production by mitochondrial complex I reverse electron transport. Antioxidants, 2019, 8(8), 285.
[] [PMID: 31390791]
Park, H-A.; Mnatsakanyan, N.; Broman, K.; Davis, A.U.; May, J.; Licznerski, P.; Crowe-White, K.M.; Lackey, K.H.; Jonas, E.A. Alpha-tocotrienol prevents oxidative stress-mediated post-translational cleavage of Bcl-xL in primary hippocampal neurons. Int. J. Mol. Sci., 2019, 21(1), 220.
[] [PMID: 31905614]
Parra, I.; Martínez, I.; Ramírez-García, G.; Tizabi, Y.; Mendieta, L. Differential effects of lps and 6-ohda on microglia’s morphology in rats: implications for inflammatory model of Parkinson’s disease. Neurotox. Res., 2020, 37(1), 1-11.
[] [PMID: 31478124]
Rasheed, M.Z.; Tabassum, H.; Parvez, S. Mitochondrial permeability transition pore: a promising target for the treatment of Parkinson’s disease. Protoplasma, 2017, 254(1), 33-42.
[] [PMID: 26825389]
Sako, K.; Futamura, Y.; Shimizu, T.; Matsui, A.; Hirano, H.; Kondoh, Y.; Muroi, M.; Aono, H.; Tanaka, M.; Honda, K.; Shimizu, K.; Kawatani, M.; Nakano, T.; Osada, H.; Noguchi, K.; Seki, M. Inhibition of mitochondrial complex I by the novel compound FSL0260 enhances high salinity-stress tolerance in Arabidopsis thaliana. Sci. Rep., 2020, 10(1), 8691.
[] [PMID: 32457324]
Samad, N. Rice bran oil prevents neuroleptic-induced extrapyramidal symptoms in rats: Possible antioxidant mechanisms. Yao Wu Shi Pin Fen Xi, 2015, 23(3), 370-375.
[] [PMID: 28911693]
Samad, N.; Haleem, M.A.; Haleem, D.J. Report: Protective effects of rice bran oil in haloperidol-induced tardive dyskinesia and serotonergic responses in rats. Pak. J. Pharm. Sci., 2016, 29(4)(Suppl.), 1467-1471.
[PMID: 27592482]
Samad, N.; Haleem, D.J. Antioxidant effects of rice bran oil mitigate repeated haloperidol-induced tardive dyskinesia in male rats. Metab. Brain Dis., 2017, 32(4), 1099-1107.
[] [PMID: 28374238]
Sharma, N.; Jamwal, S.; Kumar, P. Beneficial effect of antidepressants against rotenone induced Parkinsonism like symptoms in rats. Pathophysiology, 2016, 23(2), 123-134.
[] [PMID: 26996500]
Shripathi Acharya, G.; Acharya, M.R.S. Role of ayurveda medicine in the management of neurological disorders. IJRMST, 2020.
Sood, S.; Kumar, M.; Bansal, N. Ethanol extract of Epipremnum aureum leaves attenuate intranigral-rotenone induced Parkinson’s disease in rats. J. Pharm. Pharmacogn. Res., 2020, 8(3), 225-236.
Singanusong, R.; Garba, U. Micronutrients in Rice Bran Oil. In: Rice Bran and Rice Bran Oil; Elsevier, 2019; pp. 125-158.
Sun, C.; Wang, Y.; Mo, M.; Song, C.; Wang, X.; Chen, S.; Liu, Y. Minocycline protects against rotenone-induced neurotoxicity correlating with upregulation of Nurr1 in a Parkinson’s disease rat model. BioMed Res. Int., 2019, 2019, 6843265.
[] [PMID: 30949504]
Tanideh, N.; Sadeghi, F.; Amanat, S.; Firoozi, D.; Noorafshan, A.; Iraji, A.; Koohi-Hosseinabadi, O. Protection by pure and genistein fortified extra virgin olive oil, canola oil, and rice bran oil against acetic acid-induced ulcerative colitis in rats. Food Funct., 2020, 11(1), 860-870.
[] [PMID: 31942583]
Tseng, H-C.; Wang, M-H.; Chang, K-C.; Soung, H-S.; Fang, C-H.; Lin, Y-W.; Li, K.Y.; Yang, C.C.; Tsai, C.C. Protective Effect of (-)Epigallocatechin-3-gallate on Rotenone-Induced Parkinsonism-like Symptoms in Rats. Neurotox. Res., 2020, 37(3), 669-682.
[] [PMID: 31811588]
Vajdi-Hokmabad, R.; Ziaee, M.; Sadigh-Eteghad, S.; Sandoghchian Shotorbani, S.; Mahmoudi, J. Modafinil improves catalepsy in a rat 6-hydroxydopamine model of parkinson’s disease; possible involvement of dopaminergic neurotransmission. Adv. Pharm. Bull., 2017, 7(3), 359-365.
[] [PMID: 29071217]
Wills, E.D. Mechanisms of lipid peroxide formation in animal tissues. Biochem. J., 1966, 99(3), 667-676.
[] [PMID: 5964963]
Wong, S.K.; Kamisah, Y.; Mohamed, N.; Muhammad, N.; Masbah, N.; Fahami, N.A.M.; Mohamed, I.N.; Shuid, A.N.; Saad, Q.M.; Abdullah, A.; Mohamad, N.V.; Ibrahim, N.I.; Pang, K.L.; Chow, Y.Y.; Thong, B.K.S.; Subramaniam, S.; Chan, C.Y.; Ima-Nirwana, S.; Chin, A.K. Potential role of tocotrienols on non- communicable diseases: A review of current evidence. Nutrients, 2020, 12(1), 259.
[] [PMID: 31963885]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 25 January, 2021
Page: [428 - 438]
Pages: 11
DOI: 10.2174/1874467214666210126113324
Price: $65

Article Metrics

PDF: 150