Evaluating the effect of α-pinene on motor activity, avoidance memory and lipid peroxidation in animal model of Parkinson disease in adult male rats

Document Type : Original paper


Department of Biology, Faculty of Sciences, Izeh Branch, Islamic Azad University, Izeh, Iran.


Background and objectives: Parkinson's disease (PD) is a common neuropathologic disorder that is caused by degeneration of dopaminergic neurons of dense part of nigra. Oxidative stress has been found in the pathophysiology of PD. Since α-pinene has strong anti-oxidant effects, the purpose of this research was to study its effects on movement disorders and memory and lipid peroxidation in PD. Methods: Thirty five male rats were divided in 5 groups: control, vehicle, PD (received injection of 6-hydroxydopamine (6-OHDA)) and Parkinson's groups receiving doses of 100 and 200 mg/kg via gavage for two weeks. Generating animal models for Parkinson was done by intracerebral injection of 6-OHDA in the left side of the brain in medial forebrain bundle (MFB). After the injection, the movement balance of the rats was measured by Rotarod. Memory test was done by shuttle box; their brain was extracted to analyze malondialdehyde (MDA) in striatum, hippocampus and blood. Results: The  results showed that Parkinson caused, movement disorder (p<0.01), avoidance memory reduction (p<0.001) and malondialdehyde accumulation in hippocampus (p<0.05) and striatum (p<0.001) tissues and in blood (p<0.001). Administration of 200 and 100 mg/kg α-pinene improved the movement disorder (p<0.05). Administration of both doses of 200 and 100mg/kg showed improvement in avoidance memory (p<0.001) and (p<0.01), respectively. Malondialdehyde showed reduction in striatum (p<0.001) and hippocampus (p<0.05, p<0.001), respectively in the treatment groups after administration of both doses. In the blood, the dose of 200 α-pinene significantly reduced MDA in the tretment groups. Conclosion: The results of this research show that α-pinene could reduce the symptoms of PD in rats.


[1] De Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006; 5(6): 525-535.
[2] Betarbet R, Sherer TB, Greenamyre JT. Aanimal models of Parkinson's disease. Bioessays. 2002; 24(4): 308-318.
[3] Sarkaki A, Eidypour Z, Motamedi F, Keramati K, Farbood Y. Motor disturbances and thalamic electrical power of frequency bands' improve by grape seed extract in animal model of Parkinson's disease. Avicenna J Phytomed .2012; 2(4): 222-232.
[4] Kim ST, Son HJ, Choi JH, Ji IJ, Hwang O. Vertical grid test and modified horizontal grid test are sensitive methods for evaluating motor dysfunctions in the MPTP mouse model of Parkinson's disease. Brain Res. 2010; 1306: 176-183.
[5] Schindehutte J, Trenkwalder C. Treatment of drug-induced psychosis in Parkinson's disease with ziprasidone can induce severe dose-dependent off-periods and pathological laughing. Clin Neurol Neurosur. 2007; 109(2): 188-191.
[6] Cadet JL, Last R, Kostic V, Przedborski S, Jackson-Lewis V. Long-term behavioral and biochemical effects of 6-hydroxydopamine injections in rat caudate-putamen. Brain Res Bull.1991; 26(5): 707-713.
[7] Schwarting RK, Huston JP. Behavioral and neurochemical dynamics of neurotoxic meso-striatal dopamine lesions. Neurotoxicology.1997; 18(3): 689-708.
[8] Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron. 2003; 39(6): 889-909.
[9] Valenzuela A, Garrido A. Biochemical bases of the pharmacological action of the flavonoid silymarin and of its structural isomer silibinin. Biol Res. 1994; 27(2): 105-112.
[10] Ebadi M, Srinivasan SK, Baxi MD. Oxidative stress and antioxidant therapy in Parkinson's disease.Prog Neurobiol. 1996; 48(1): 1-19.
[11] Craig WJ. Health-promoting properties of common herbs. Am J Clin Nutr.1999; 70(3 Suppl): 491-499.
[12] Jay TM. Dopamine: a potential substrate for synaptic plasticity and memory mechanisms. Prog Neurobiol. 2003; 69(6): 375-390.
[13] Nail-Boucherie K, Dourmap N, Jaffard R, Costentin J. The specific dopamine uptake inhibitor GBR 12783 improves learning of inhibitory avoidance and increases hippocampal acetylcholine release. Brain Res. 1998; 7(2): 203-205.
[14] Packard MG, White NM. Memory facilitation produced by dopamine agonists: role of receptor subtype and mnemonic requirements. Pharmacol Biochem Behav.  1989; 33(3): 511-518.
[15] Bernabeu R, Bevilaqua L, Ardenghi P, Bromberg E, Schmitz P, Bianchin M, Izquierdo I, Medina JH. Involvement of hippocampal cAMP/cAMP-dependent protein kinase signaling pathways in a late memory consolidation phase of aversively motivated learning in rats. Proc Natl Acad Sci USA. 1997; 94(13): 7041-7046.
[16] Wilkerson A, Levin ED. Ventral hippocampal dopamine D1 and D2 systems and spatial working memory in rats. Neuroscience. 1999; 89(3): 743-749.
[17] Watson GS, Leverenz JB. Profile of cognitive impairment in Parkinson's disease. Brain Pathol. 2010; 20(3): 640-645.
[18] Rektorova I. Mild cognitive impairment exists in Parkinson's disease.J Neural Transm. 2011; 118(8): 1179-1183.
[19] Sadraei H, Shokoohinia Y, Sajjadi SE, Ghadirian B. Antispasmodic effect of osthole and Prangos ferulacea extract on rat uterus smooth muscle motility. Res Pharm Sci. 2012; 7(3): 141-149.
[20] Jerkovic I, Marasovic M, Marijanovic Z, Pilepic KH, Males Z, Milos M. Chemical composition of Hypericum richeri subsp. grisebachii essential oil from Croatia. Nat Prod Commun.2013; 8(2): 231-233.
[21] Sadraei H, Asghari GR, Hajhashemi V, Kolagar A, Ebrahimi M. Spasmolytic activity of essential oil and various extracts of Ferula gummosa Boiss. on ileum contractions. Phytomedicine. 2001; 8(5): 370-376.
[22] Sonboli A, Bahadori MB, Dehghan H, Aarabi L, Savehdroudi P, Nekuei M, Pournaghi N, Mirzania F. Chemotaxonomic importance of the essential-oil composition in two subspecies of Teucrium stocksianum Boiss. from Iran. Chem Biodivers. 2013; 10(4): 687-694.
[23] Abu-Darwish MS, Cabral C, Ferreira IV, Goncalves MJ, Cavaleiro C, Cruz MT, Al-bdour TH, Salgueiro L. Essential oil of common sage (Salvia officinalis L.) from Jordan: assessment of safety in mammalian cells and its antifungal and anti-inflammatory potential. Biomed Res Int. 2013; Article ID 538940.
[24] Heidari S, Akrami H, Gharaei R, Jalili A, Mahdiuni H, Golezar E. Anti-tumor activity of Ferulago angulata Boiss. extract in gastric cancer cell line via induction of apoptosis. Iran J Pharm Res. 2014; 13(4): 1335-1345.
[25] Haj-Husein I, Tukan S, Alkazaleh F. The effect of marjoram (Origanum majorana) tea on the hormonal profile of women with polycystic ovary syndrome: a randomised controlled pilot study.J Hum Nutr Diet.  2016; 29(1): 105-111.
[26] Mirza M, Nik ZB. Extraction and identification of the essential oil components of Salvia lachnocalyx Hedge.  Iran J Med Aromatic Plants.2007; 23(20): 278-284.
[27] Griffiths ET, Bociek SM, Harries PC, Jeffcoat R, Sissons DJ, Trudgill PW. Bacterial metabolism of alpha-pinene: pathway from alpha-pinene oxide to acyclic metabolites in Nocardia sp. strain P18.3. J Bacteriol.1987; 169(11): 4972-4979.
[28] McPartland JM, Pruitt PL. Side effects of pharmaceuticals not elicited by comparable herbal medicines: the case of tetrahydrocannabinol and marijuana. Altern Ther Health Med. 1999; 5(4): 57-62.
[29] Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. A review on therapeutic potential of Nigella sativa: a miracle herb. Asian Pac J Trop Biomed. 2013; 3(5): 337-352.
[30] Consroe P, Martin A, Singh V. Antiepileptic potential of cannabidiol analogs. J Clin Pharmacol.1981; 21(8-9 Suppl): 428S-436S.
[31] Singh HP, Batish DR, Kaur S, Arora K, Kohli RK. α-Pinene inhibits growth and induces oxidative stress in roots. Ann Bot. 2006; 98(6): 1261-1269.
[32] Eftekhar F, Yousefzadi M, Borhani K. Antibacterial activity of the essential oil from Ferula gummosa seed. Fitoterapia. 2004; 75(7-8): 758-759.
[33] Kim DS, Lee HJ, Jeon YD, Han YH, Kee JY, Kim HJ,  Kim SJ, Park SH, Choi BM, Park SJ, Um JY, Hong SH. α-Pinene exhibits anti-inflammatory activity through the suppression of mapks and the nf-kappab pathway in mouse peritoneal macrophages. Am J Chin Med. 2015; 43(4): 731-742.
[34] Chen W, Liu Y, Li M, Mao J, Zhang L, Huang R, Jin X, Ye L. Anti-tumor effect of alpha-pinene on human hepatoma cell lines through inducing G2/M cell cycle arrest. J Pharmacol Sci. 2015; 127(3): 332-338.
[35] Sandeep B, Veeresh B. Pre-clinical evolutionary study of alpha-pinene in l-arginine induced acute pancreatitis in rat. Indian J Pharm Edu Res. 2013; 47(4): 73-78.
[36] Farbood Y, Sarkaki A, Dolatshahi M, Taqhi Mansouri SM, Khodadadi A. Ellagic acid protects the brain against 6-hydroxydopamine induced neuroinflammation in a rat model of Parkinson's disease. Basic Clin Neurosci.2015; 6(2): 83-89.
[37] Duty S, Jenner P. Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease. Brit J Pharmacol. 2011; 164(4): 1357-1391.
[38] Mirzapour S, Rafieirad M, Rouhi L. Hydroalcoholic extract of Ferulago angulata improves memory and pain in brain hypoperfusion ischemia in rats. Jundishapur J Nat Pharm Prod.2015; 10(1): 24-37.
[39] Sharifi F, Rafieirad M, Sazegar H. Effects of Ferulago angulata extract against oxidative stress induced by 6-hydroxydopamine in rats. J Med Plants. 2015; 1(53): 34-44.
[40] Van Kampen J, Robertson H, Hagg T, Drobitch R. Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson's disease. Exp Neurol. 2003; 184(1): 521-529.
[41] Kim MS, Lee JI, Lee WY, Kim SE. Neuroprotective effect of Ginkgo biloba L. extract in a rat model of Parkinson's disease. Phytother Res. 2004; 18(8): 663-666.
[42] Schwarting RK, Huston JP. The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments. Prog Neurobiol.1996; 50(2-3): 275-331.
[43] Salar F, Ziai SA, Nasri S, Roghani M, Kamalinegad M. Neuroprotective effect of aqueous extract of Berberis vulgaris L. in a model of Parkinson’s disease in rat. J Med Plants. 2010; 4(36): 24-33.
[44] Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson's disease. J Parkinsons Dis.2013; 3(4): 461-491.
[45] Hwang O. Role of oxidative stress in Parkinson's disease. Exp Neurobiol. 2013; 22(1): 11-17.
[46] Dani C, Pasquali MA, Oliveira MR, Umezu FM, Salvador M, Henriques JA, Moreira JC. Protective effects of purple grape juice on carbon tetrachloride-induced oxidative stress in brains of adult Wistar rats.J Med Food.2008; 11(1): 55-61.
[47] Gil ML, Jimenez J, Ocete MA, Zarzuelo A, Cabo MM. Comparative study of different essential oils of Bupleurum gibraltaricum Lamarck. Die Pharmazie. 1989; 44(4): 284-287.
[48] Aiyegoro OA,  Vandyk S. The antioxidant properties, cytotoxicity and monoamine oxidase inhibition abilities of the crude dichloromethane extract of Tarchonanthus camphoratus L. leaves. African J Biotechnol. 2011; 10(75): 17297-17304.
[49] Ziemba PM, Schreiner BS, Flegel C, Herbrechter R, Stark TD, Hofmann T, Hatt H, Werner M, Gisselmann G. Activation and modulation of recombinantly expressed serotonin receptor type 3A by terpenes and pungent substances. Biochem Biophys Res Commun.2015; 467(4): 1090-1096.
[50] Zhang H, Han T, Zhang L, Yu CH, Wan DG, Rahman K, Qin LP, Peng C. Effects of tenuifolin extracted from radix polygalae on learning and memory: a behavioral and biochemical study on aged and amnesic mice. Phytomedicine. 2008; 15(8): 587-594.
[51] Juca DM, da Silva MT, Junior RC, de Lima FJ, Okoba W, Lahlou S, de Oliveira RB, dos Santos AA, Magalhaes PJ. The essential oil of Eucalyptus tereticornis and its constituents, alpha- and beta-pinene, show accelerative properties on rat gastrointestinal transit. Planta Med. 2011; 77(1): 57-59.
[52] Rajendran MP, Pallaiyan BB, Selvaraj N. Chemical composition, antibacterial and antioxidant profile of essential oil from Murraya koenigii (L.) leaves. Avicenna J Phytomed. 2014; 4(3): 200-214.
[53] Picollo MI, Toloza AC, Mougabure Cueto G, Zygadlo J, Zerba E. Anticholinesterase and pediculicidal activities of monoterpenoids. Fitoterapia. 2008; 79(4): 271-278.
[54] Yu Z, Wang B, Yang F, Sun Q, Yang Z, Zhu L. Chemical composition and anti-acetyl cholinesterase activity of flower essential oils of Artemisia annua at different flowering stage. Iran J Pharm Res. 2011; 10(2): 265-271.
[55] Savelev SU, Okello EJ, Perry EK. Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents. Phytother Res.2004; 18(4): 315-324.
[56] Kessler A, Sahin-Nadeem H, Lummis SC, Weigel I, Pischetsrieder M, Buettner A, Villmann C. GABA (A) receptor modulation by terpenoids from Sideritis extracts.Mol Nutr Food Res. 2014; 58(4): 851-862.