Accessible Unlicensed Requires Authentication Published by De Gruyter June 28, 2016

In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells

María Porres-Martínez, Elena González-Burgos, M. Emilia Carretero and M. Pilar Gómez-Serranillos

Abstract

Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Natural products are considered as therapeutically useful antioxidant agents against reactive oxygen species (ROS). We have evaluated the antioxidant and protective potential of the monoterpenes 1,8-cineole and α-pinene against H2O2-induced oxidative stress in PC12 (rat pheochromocytoma) cells. Pretreatment with these monoterpenes was found to attenuate the loss of cell viability and the changes in cell morphology. Moreover, they inhibited the intracellular ROS production and markedly enhanced the expression of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and heme-oxygenase 1 (HO-1). In addition, they were able to decrease apoptosis as is evident from reduced capase-3 activity. The mechanisms of their antioxidant action appear to involve ROS scavenging and induction of the nuclear Nrf2 factor. This study demonstrates the potential beneficial therapeutic effect of these common monoterpenes on the oxidant/antioxidant balance in diseases of the nervous system.

References

1. Gilgun-Sherki Y, Melamed E, Offen D. Oxidative stress induced-neurodegenerative diseases: The need for antioxidants that penetrate the blood brain barrier. Neuropharmacol 2001;40:959–75.Search in Google Scholar

2. Floyd R-A, Hensley K. Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging 2002;23:795–807.Search in Google Scholar

3. Rao K-S. Free radical induced oxidative damage to DNA: relation to brain aging and neurological disorders. Indian J Biochem Biophys 2009;46:9–15.Search in Google Scholar

4. Sayre L-M, Perry G, Smith M-A. Oxidative stress and neurotoxicity. Chem Res Toxicol 2008;21:172–88.Search in Google Scholar

5. Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 2004;142:231–55.Search in Google Scholar

6. Wijeratne S-S, Cuppett S-L, Schlegel V. Hydrogen peroxide induced oxidative stress damage and antioxidant enzyme response in Caco-2 human colon cells. J Agric Food Chem 2005;53:8768–74.Search in Google Scholar

7. Singh M, Murthy V, Ramassamy C. Modulation of hydrogen peroxide and acrolein-induced oxidative stress, mitochondrial dysfunctions and redox regulated pathways by the Bacopa monniera extract: potential implication in Alzheimer’s disease. J Alzheimers Dis 2010;21:229–47.Search in Google Scholar

8. Zhu D, Tan K-S, Zhang X, Sun A-Y, Sun G-Y, Lee J-C. Hydrogen peroxide alters membrane and cytoskeleton properties and increases intercellular connections in astrocytes. J Cell Sci 2005;118:3695–703.Search in Google Scholar

9. Mayne S-T. Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. J Nutr 2003;133:933S–40S.Search in Google Scholar

10. Devasagayam T-P, Tilak J-C, Boloor K-K, Sane K-S, Ghaskadbi S-S, Lele RD. Free radicals and antioxidants in human health: Current status and future prospects. J Assoc Physicians India 2004;52:794–803.Search in Google Scholar

11. Sindhi V, Gupta V, Sharma K, Bhatnagar S, Kumari R, Dhaka N. Potential applications of antioxidants – A review. J Pharm Res 2013;7:828–35.Search in Google Scholar

12. Imosemi I-O. The role of antioxidants in cerebellar development. A review of literature. Int J Morphol 2013;31:203–10.Search in Google Scholar

13. Iriti M, Vitalini S, Fico G, Faoro F. Neuroprotective herbs and foods from different traditional medicines and diets. Molecules 2010;15:3517–55.Search in Google Scholar

14. Porres-Martínez M, González-Burgos E, Carretero M-E, Gómez-Serranillos M-P. Phytochemical composition, antioxidant and cytoprotective activities of essential oil of Salvia lavandulifolia Vahl. Food Res Int 2013;54:523–31.Search in Google Scholar

15. González-Burgos E, Gómez-Serranillos M-P. Terpene compounds in the nature: a review of their potential antioxidant activity. Curr Med Chem 2012;19:5319–41.Search in Google Scholar

16. Elaissi A, Rouis Z, Mabrouk S, Salah K-B, Aouni M, Khouja M-L, et al. Correlation between chemical composition and antibacterial activity of essential oils from fifteen Eucalyptus species growing in the Korbous and Jbel Abderrahman arboreta (North East Tunisia). Molecules 2012;17:3044–57.Search in Google Scholar

17. Santos F-A, Rao V-S. Antiinflammatory and antinociceptive effects of 1,8-cineole, a terpenoid oxide present in many plant essential oils. Phytother Res 2000;14:240–4.Search in Google Scholar

18. Santos F-A, Silva R-M, Campos A-R, de Araujo R-P, Lima Junior R-C, Rao V-S. 1,8-Cineole (eucalyptol), a monoterpene oxide, attenuates the colonic damage in rats on acute TNBS-colitis. Food Chem Toxicol 2004;42:579–84.Search in Google Scholar

19. Juergens U-R, Engelen T, Racké K, Söber M, Gillissen A, Vetter H. Inhibitory activity of 1,8-cineol (eucalyptol) on cytokine production in cultured human lymphocytes and monocytes. Pulm Pharmacol Ther 2004;17:281–7.Search in Google Scholar

20. Cho KH. 1,8-cineole protected human lipoproteins from modification by oxidation and glycation and exhibited serum lipid-lowering and anti-inflammatory activity in zebrafish. BMB Rep 2012;45:565–70.Search in Google Scholar

21. Caputi L, Aprea E. Use of terpenoids as natural flavouring compounds in food industry. Recent Pat Food Nutr Agric 2011;3:9–16.Search in Google Scholar

22. Miyazawa M, Yamafuji C. Inhibition of acetylcholinesterase activity by bicyclic monoterpenoids. J Agric Food Chem 2005;53:1765–8.Search in Google Scholar

23. Chang H, Kim H-J, Chun HS. Quantitative structure-activity relationship (QSAR) for neuroprotective activity of terpenoids. Life Sci 2007;80:835–41.Search in Google Scholar

24. Astani A, Reichling J, Schnitzler P. Comparative study on the antiviral activity of selected monoterpenes derived from essential oils. Phytother Res 2009;24:673–9.Search in Google Scholar

25. Bae G-S, Park K-C, Choi S-B, Jo I-J, Choi M-O, Hong S-H, et al. Protective effects of alpha-pinene in mice with cerulein-induced acute pancreatitis. Life Sci 2012;91:866–71.Search in Google Scholar

26. Matsuo A-L, Figueiredo C-R, Arruda D-C, Pereira F-V, Borin Scutti J-A, Massaoka M-H, et al. α-Pinene isolated from Schinus terebinthifolius Raddi (Anacardiaceae) induces apoptosis and confers antimetastatic protection in a melanoma model. Biochem. Biophys Res Comm 2011;411:449–54.Search in Google Scholar

27. Türkez H, Aydin E. In vitro assessment of cytogenetic and oxidative effects of α-pinene. Toxicol. Ind Health 2013.PMID: 24081629.Search in Google Scholar

28. Aydin E, Türkez H, Geyikoğlu F. Antioxidative, anticancer and genotoxic properties of α-pinene on N2a neuroblastoma cells. Biologia 2013;68:1004–9.Search in Google Scholar

29. Mosmann T. Rapid colorimetric assay for celular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55–63.Search in Google Scholar

30. LeBel C-P, Ischiropoulos H, Bondy S-C. Evaluation of the probe 2,7- dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 1992;5:227–31.Search in Google Scholar

31. Smith P-K, Krohn R-I, Hermanson G-T, Mallia A-K, Gartner F-H, Provenzano M-D, et al. Measurement of protein using bicinchoninic acid. Anal Biochem 1985;150:76–85.Search in Google Scholar

32. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271–8.Search in Google Scholar

33. Trippier P-C, Jansen Labby K, Hawker D-D, Mataka J-J, Silverman R-B. Target- and mechanism-based therapeutics for neurodegenerative diseases: strength in numbers. J Med Chem 2013;56:3121–47.Search in Google Scholar

34. Suzuki T, Motohashi H, Yamamoto M. Toward clinical application of the Keap1-Nrf2 pathway. Trends Pharmacol Sci 2013;34: 340–6.Search in Google Scholar

35. Zhang M, An C, Gao Y, Leak R-K, Chen J, Zhang F. Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Progr Neurobiol 2013;100:30–47.Search in Google Scholar

36. Blomgren K, Leist M, Groc L. Pathological apoptosis in the developing brain. Apoptosis 2007;12:993–1010.Search in Google Scholar

37. Kumar G-P, Anilakumar K-R, Naveen S. Phytochemicals having neuroprotective properties from dietary sources and medicinal herbs. Pharmacog J 2015;7:1–17.Search in Google Scholar

38. Perry N-S, Houghton P-J, Theobald A, Jenner P, Perry E-K. In-vitro inhibition of erythrocyte acetylcholinesterase by Salvia lavandulifolia essential oil and constituent terpenes. J Pharm Pharmacol 2000;52:1347–56.Search in Google Scholar

39. Zhang C, Chen S, Bao J, Zhang Y, Huang B, Jia X, et al. Low doses of camptothecin induced hormetic and neuroprotective effects in PC12 cells. Dose-Response 2015;13:1–7.Search in Google Scholar

Received: 2014-8-1
Revised: 2016-3-13
Accepted: 2016-4-17
Published Online: 2016-6-28
Published in Print: 2016-7-1

©2016 Walter de Gruyter GmbH, Berlin/Boston