Abstract
Hempseed is rich in polyunsaturated fatty acids (PUFAs), which have potential as therapeutic compounds for the treatment of neurodegenerative and cardiovascular disease. However, the effect of hempseed meal (HSM) intake on the animal models of these diseases has yet to be elucidated. In this study, we assessed the effects of the intake of HSM and PUFAs on oxidative stress, cytotoxicity and neurological phenotypes, and cholesterol uptake, using Drosophila models. HSM intake was shown to reduce H2O2 toxicity markedly, indicating that HSM exerts a profound antioxidant effect. Meanwhile, intake of HSM, as well as linoleic or linolenic acids (major PUFA components of HSM) was shown to ameliorate Aβ42-induced eye degeneration, thus suggesting that these compounds exert a protective effect against Aβ42 cytotoxicity. On the contrary, locomotion and longevity in the Parkinson’s disease model and eye degeneration in the Huntington’s disease model were unaffected by HSM feeding. Additionally, intake of HSM or linoleic acid was shown to reduce cholesterol uptake significantly. Moreover, linoleic acid intake has been shown to delay pupariation, and cholesterol feeding rescued the linoleic acid-induced larval growth delay, thereby indicating that linoleic acid acts antagonistically with cholesterol during larval growth. In conclusion, our results indicate that HSM and linoleic acid exert inhibitory effects on both Aβ42 cytotoxicity and cholesterol uptake, and are potential candidates for the treatment of Alzheimer’s disease and cardiovascular disease.
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References
Al-Khalifa, A., Maddaford, T.G., and Chahine, M.N. (2007). Effect of dietary hempseed intake on cardiac ischemia-reperfusion injury. American journal of physiology. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, 1198–1203.
Alvaro, A., Rosales, R., Masana, L., and Vallvé, J.C. (2010). Polyunsaturated fatty acids down-regulate in vitro expression of the key intestinal cholesterol absorption protein NPC1L1: no effect of monounsaturated nor saturated fatty acids. J. Nutr. Biochem. 21, 518–525.
Bouzidi, N., Mekki, K., Boukaddoum, A., Dida, N., Kaddous, A., and Bouchenak, M. (2010). Effects of omega-3 polyunsaturated fatty-acid supplementation on redox status in chronic renal failure patients with dyslipidemia. J. Ren. Nutr. 5, 321–328.
Callaway, J.C. (2004). Hempseed as a nutritional resource: an overview. Euphytica 140, 65–72.
Callaway, J., Schwab, U., Harvima, I., Halonen, P., Mykkänen, O., Hyvönen, P., and Järvinen, T. (2005). Efficacy of dietary hempseed oil in patients with atopic dermatitis. J. Dermatolog. Treat. 16, 87–94.
Casós, K., Zaragozá, M.C., Zarkovic, N., Zarkovic, K., Andrisic, L., Portero-Otín, M., Cacabelos, D., and Mitjavila, M.T. (2010). A fish oil-rich diet reduces vascular oxidative stress in apoE (−/−) mice. Free Radic. Res. 44, 821–829.
Cha, G.H., Kim, S., Park, J., Lee, E., Kim, M., Lee, S.B., Kim, J.M., Chung, J., and Cho, K.S. (2005). Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. Proc. Natl. Acad. Sci. USA 102, 10345–10350.
Das, U.N., and Vaddadi, K.S. (2004). Essential fatty acids in Huntington’s disease. Nutrition 20, 942–947.
Delattre, A.M., Kiss, A., Szawka, R.E., Anselmo-Franci, J.A., Bagatini, P.B., Xavier, L.L., Rigon, P., Achaval, M., Iagher, F., de David, C., et al. (2010). Evaluation of chronic omega-3 fatty acids supplementation on behavioral and neurochemical alterations in 6-hydroxydopamine-lesion model of Parkinson’s disease. Neurosci. Res. 66, 256–264.
de Padua, L.S., Bunyaprafatsara, N., and Lemmens, R.H.M.J. (1999). Plant resources of South-East Asia: medicinal and poisonous plants. (Leiden: Backhuys Publishers).
Feany, M.B., and Bender, W.W. (2000). A Drosophila model of Parkinson’s disease. Nature 404, 394–398.
Fedor, D., and Kelley, D.S. (2009). Prevention of insulin resistance by n-3 polyunsaturated fatty acids. Curr. Opin. Clin. Nutr. Metab. Care 12, 138–146.
Finelli, A., Kelkar, A., Song, H.J., Yang, H., and Konsolaki, M. (2004). A model for studying Alzheimer’s Abeta42-induced toxicity in Drosophila melanogaster. Mol. Cell. Neurosci. 26, 365–375.
Florent, S., Malaplate-Armand, C., Youssef, I., Kriem, B., Koziel, V., Escanyé, M.C., Fifre, A., Sponne, I., Leininger-Muller, B., Olivier, J.L., et al. (2006). Docosahexaenoic acid prevents neuronal apoptosis induced by soluble amyloid-beta oligomers. J. Neuroche. 96, 385–895.
Florent-Béchard, S., Desbène, C., Garcia, P., Allouche, A., Youssef, I., Escanyé, M.C., Koziel, V., Hanse, M., Malaplate-Armand, C., Stenger, C., et al. (2009). The essential role of lipids in Alzheimer’s disease. Biochimie 91, 804–809.
Fluegel, M.L., Parker, T.J., and Pallanck, L.J. (2006). Mutations of a Drosophila NPC1 gene confer sterol and ecdysone metabolic defects. Genetics 172, 185–196.
Harris, W.S. (2008). Linoleic acid and coronary heart disease. Prostaglandins Leukot. Essent. Fatty Acids 79, 169–171.
Hashimoto, M., Hossain, S., Shimada, T., Sugioka, K., Yamasaki, H., Fujii, Y., Ishibashi, Y., Oka, J., and Shido, O. (2002). Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer’s disease model rats. J. Neurochem. 81, 1084–1091.
Holub, D.J., and Holub, B.J. (2004). Omega-3 fatty acids from fish oils and cardiovascular disease. Mol. Cell. Biochem. 263, 217–225.
Horner, M.A., Pardee, K., Liu, S., King-Jones, K., Lajoie, G., Edwards, A., Krause, H.M., and Thummel, C.S. (2009). The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis. Genes Dev. 23, 2711–2716.
Kim, E.S., and Mahlberg, P.G. (2003). Secretory vesicle formation in the secretory cavity of glandular trichomes of Cannabis sativa L. (cannabaceae). Mol. Cells 15, 387–395.
Kim, S.J., Zhang, Z., Saha, A., Sarkar, C., Zhao, Z., Xu, Y., and Mukherjee, A.B. (2010). Omega-3 and omega-6 fatty acids suppress ER- and oxidative stress in cultured neurons and neuronal progenitor cells from mice lacking PPT1. Neurosci. Lett. 479, 292–296.
Lee, K.M., Jang, J.H., Park, J.S., Kim, D.S., and Han, H.S. (2009). Effect of mild hypothermia on blood brain barrier disruption induced by oleic acid in rats. Genes Genomics 31, 89–98.
Lee, M.J., Park, M.S., Hwang, S., Hong, Y.K., Choi, G., Suh, Y.S., Han, S.Y., Kim, D., Jeun, J., Oh, C.T., et al. (2010). Dietary hempseed meal intake increases body growth and shortens the larval stage via the upregulation of cell growth and sterol levels in Drosophila melanogaster. Mol. Cells 30, 29–36.
Malini, T., and Vanithakumari, G. (1990). Rat toxicity studies with β-sitosterol. J. Ethnopharmacol. 28, 221–234.
Matthäus, B., and Brühl, L. (2008). Virgin hempseed oil: an interesting niche product. Eur. J. Lipid Sci. Technol. 110, 655–661.
Miettinen, T.A., and Gylling, H. (2004) Plant stanol and sterol esters in prevention of cardiovascular diseases. Ann. Med. 36, 126–134.
Patch, C.S., Tapsell, L.C., Williams, P.G., and Gordon, M. (2006). Plant sterols as dietary adjuvants in the reduction of cardiovascular risk: theory and evidence. Vasc. Health Risk Manag. 2, 157–162.
Prociuk, M., Edel, A., Gavel, N., Deniset, J., Ganguly, R., Austria, J., Ander, B., Lukas, A., and Pierce, G. (2006). The effects of dietary hempseed on cardiac ischemia/reperfusion injury in hypercholesterolemic rabbits. Exp. Clin. Cardiol. 11, 198–205.
Prociuk, M.A., Edel, A.L., Richard, M.N., Gavel, N.T., Ander, B.P., Dupasquier, C.M., and Pierce, G.N. (2008). Cholesterol-induced stimulation of platelet aggregation is prevented by a hempseed-enriched diet. Can. J. Physiol. Pharmacol. 86, 153–159.
Sampath, H., and Ntambi, J.M. (2004). Polyunsaturated fatty acid regulation of gene expression. Nutr. Rev. 62, 333–339.
Sarsilmaz, M., Songur, A., Ozyurt, H., Kuş, I., Ozen, O.A., Ozyurt, B., Söǧüt, S., and Akyol, O. (2003). Potential role of dietary omega-3 essential fatty acids on some oxidant/antioxi-dant parameters in rats’ corpus striatum. Prostaglandins Leukot. Essent. Fatty Acids 69, 253–259.
Shen, L.R., Lai, C.Q., Feng, X., Parnell, L.D., Wan, J.B., Wang, J.D., Li, D., Ordovas, J.M., and Kang, J.X. (2010). Drosophila lacks C20 and C22 PUFAs. J. Lipid Res. 51, 2985–2992.
Sullivan, W., Ashburner, M., and Hawley, R.S. (2000). Drosophila protocols. (New York: Cold Spring Harbor Laboratory Press).
Wang, X., Zhao, X., Mao, Z.Y., Wang, X.M., and Liu, Z.L. (2003). Neuroprotective effect of docosahexaenoic acid on glutamateinduced cytotoxicity in rat hippocampal cultures. Neuroreport 14, 2457–2461.
Yoshioka, T., Inoue, H., Kasama, T., Seyama, Y., Nakashima, S., Nozawa, Y., and Hotta, Y. (1985). Evidence that arachidonic acid is deficient in phosphatidylinositol of Drosophila heads. J. Biochem. 98, 657–662.
Youdim, K.A., Martin, A., and Joseph, J.A. (2000). Essential fatty acids and the brain: possible health implications. Int. J. Dev. Neurosci. 18, 383–399.
Zúñiga, J., Venegas, F., Villarreal, M., Núñez, D., Chandía, M., Valenzuela, R., Tapia, G., Varela, P., Videla, L.A., and Fernández, V. (2010). Protection against in vivo liver ischemia-reperfusion injury by n-3 long-chain polyunsaturated fatty acids in the rat. Free Radic. Res. 44, 854–863.
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Lee, M.J., Park, S.H., Han, J.H. et al. The effects of hempseed meal intake and linoleic acid on Drosophila models of neurodegenerative diseases and hypercholesterolemia. Mol Cells 31, 337–342 (2011). https://doi.org/10.1007/s10059-011-0042-6
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DOI: https://doi.org/10.1007/s10059-011-0042-6