Effect of Carica papaya L. Extract Protect Against Oxidative Stress in Rat Model of Focal Cerebral Ischemia
Abstract
Stroke has been recognized as one of the most dangerous killer diseases in Thailand and worldwide. It has been reported that stroke is the common cause of neurological problems that mainly found leads to mortality or disability problems. However, the effective protective and therapeutic strategies had not effective. Therefore, this study is carried out to screening the neuroprotective effect of Carica papaya L. extract against cerebral ischemia. Rats were fed with 50, 150 and 450 mg / kg ripe papaya extract for 14 days prior to induce middle cerebral artery. Then, the rats were measure the brain infarction volume and oxidative markers. The results demonstrated that all doses of Carica papaya L. extract reduced brain infarction volume in the cortex striatum and hippocampus. In addition, the lipid peroxidation product was decreased, increased the activity of glutathione peroxidase (GSH.px) superoxide dismutase (SOD) and catalase (CAT) in cortex. The spatial memory had been increase according to reduce the escape latency time at dose 150 and 450 mg/kg BW in Healthy Condition. Therefore, in conclusion, Carica papaya L. extract has potential to be developed as a novel effective therapeutic agent against ischemic stroke. However, further study on the other pathways in cerebral ischemia has to be conducted for elucidating the precise mechanism of action. Keywords: cerebral artery occlusion, papaya extract, animal model of stroke, scavenging enzymeReferences
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Barbagallo, M., Marotta F., & Dominguez, L.J. (2015). Oxidative stress in patients with Alzheimer’s disease: Effect of extracts of fermented papaya powder. Mediators Inflammation, 624801. 1-6.
Binthaisong, T. (2014). Arrival time in patients with acute stroke. Journal of the Police Nurse, 6 (2), 275-282.
(in Thai)
Cocate, P.G., Natali, A.J., Alfenas, R.C, de Oliveira, A., dos Santos, E.C., & Hermsdorff H.H. (2015). Carotenoid consumption is related to lower lipid oxidation and DNA damage in middle-aged men. British Journal of Nutrition, 114, 257–264.
Dhingra, D. & Kumar, V. (2012). Memory-Enhancing Activity of Palmatine in Mice Using Elevated Plus Maze and Morris Water Maze. Advances in Pharmacological Sciences, 2012, Article ID 357368, 1-7.
Goldblith, S. A., & Proctor, B. E. (1950). Photometric determination of catalase activity. Journal of Biological Chemistry, 187, 705-709.
Hara, H., Fink, K., Endres, M., Friedlander, R.M., Gagliardini, V., Yuan, J., & Moskowitz, M.A. (1997). Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein. Journal of Cerebral Blood Flow Metabolism, 17, 370-375.
Kadry, M.S. (2012). Antioxidant and immunostimulant effect of Carica papaya Linn. aqueous extract in acrylamide intoxicated rats. Acta Informatica Medica, 20 (3), 180-185.
Kokaia, Z., Thored, P., Arvidsson A., & Lindvall, O. (2006). Regulation of stroke-induced neurogenesis in adult brain—recent scientific progress. Cerebral Cortex, 16(Suppl 1), i162-i167.
Li, H., Horke, S., & Förstermann, U. (2013). Oxidative stress in vascular disease and its pharmacological prevention. Trends in Pharmacological Sciences, 34(6), 313-319.
Liu, J-Q., Dai, S-X., Zheng, J-J., Guo, Y-C., Li, W-X., Li, G-H., & Huang, J-F. (2017). The identification and molecular mechanism of anti-stroke traditional Chinese medicinal compounds. Scientific Reports, 7, 14106. 1-11.
Lo, E.H., Moskowitz, M.A., & Jacobs, T.P. (2005). Exciting, radical, suicidal: how brain cells die after stroke. Stroke, 36(2), 189-192.
Longa, E.Z., Weinstein, P.R., Carlson, S., & Cummins, R. (1989).Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 20(1), 84-91.
McCord, J.M. & Fridovich, I. (1969).Superoxide dismutase: an enzymic function for erythrocuprein (hemocuprein). Journal of Biological Chemistry, 244, 6049–6055.
Ministry of public health. (2002). Burden of disease and injuries in Thailand Priority setting for policy, A14-16, 58.
Moskowitz, M.A., Lo, E.H., & Iadecola, C. (2010). The Science of stroke: Mechanisms in search of treatments. Neuron, 67(2), 181-198.
Nimse, S.B., Pal, D. (2015). Free radicals, natural antioxidants, and their reaction mechanisms. RSC Advances,
5(35), 27986-28006.
Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Annals of Biochemistry, 95, 351–358.
Otsuki, N., Dang, N. H., Kumagai, E., Kondo A., Iwata, S., & Morimoto, C. (2010). Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. Journal of Ethnopharmacology, 127(3), 760-767.
Pongmayteegul, S. (2010). Experimental models of global and focal cerebral ischemia. Journal of Medicine and Health Sciences, 17 (3), 149 -159. (in Thai)
Parmeshwar L.S., Ishwar S.S., & Ravish, C. (2015). Papaya: Biology, cultivation, production and uses.
(pp. 169 -188). New York: CRC Press.
Sadek, K.M. (2012). Antioxidant and immunostimulant effect of Carica papaya Linn. aqueous extract in acrylamide intoxicated rats. Acta Informatica Medica, 20(3), 180-185.
Sankat, C.K., & Maharaj, R.P. (1997). In: Mitra SK. (Ed.), Postharvest physiology and storage of tropical and subtropical foods. (pp. 167-189). New York: Cab International.
Sawatdiyapanon, C., & Kaewkaen, P. (2015). Behavioral effect of Carica papaya L. fruits juice in animal model of mild cognitive impairment. In Proceedings of the Burapha University International Conference 2015. (pp. 423-429). Chon Buri: Thailand.
Wang, S., Cu, Y., Wang, C., Xie, W., Ma, L., Zhu, J. (2015). Protective effects of dietary supplementation with a combination of nutrients in a transgenic mouse Mmodel of Alzheimer’s disease. PLoS ONE, 10(11), e0143135.
Wendel, A. (1981). Glutathione peroxidase. Methods in Enzymology, 77, 325-333.
World Health Organization. (2014).Global status report on non-communicable diseases. Geneva: World Health Organization.
Zhou, L., Paull, R.E. (2001). Sucrose metabolism during papaya (Carica papaya L.) fruit growth and ripening. Journal of the American Society for Horticultural Science, 126, 351-357.
Barbagallo, M., Marotta F., & Dominguez, L.J. (2015). Oxidative stress in patients with Alzheimer’s disease: Effect of extracts of fermented papaya powder. Mediators Inflammation, 624801. 1-6.
Binthaisong, T. (2014). Arrival time in patients with acute stroke. Journal of the Police Nurse, 6 (2), 275-282.
(in Thai)
Cocate, P.G., Natali, A.J., Alfenas, R.C, de Oliveira, A., dos Santos, E.C., & Hermsdorff H.H. (2015). Carotenoid consumption is related to lower lipid oxidation and DNA damage in middle-aged men. British Journal of Nutrition, 114, 257–264.
Dhingra, D. & Kumar, V. (2012). Memory-Enhancing Activity of Palmatine in Mice Using Elevated Plus Maze and Morris Water Maze. Advances in Pharmacological Sciences, 2012, Article ID 357368, 1-7.
Goldblith, S. A., & Proctor, B. E. (1950). Photometric determination of catalase activity. Journal of Biological Chemistry, 187, 705-709.
Hara, H., Fink, K., Endres, M., Friedlander, R.M., Gagliardini, V., Yuan, J., & Moskowitz, M.A. (1997). Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein. Journal of Cerebral Blood Flow Metabolism, 17, 370-375.
Kadry, M.S. (2012). Antioxidant and immunostimulant effect of Carica papaya Linn. aqueous extract in acrylamide intoxicated rats. Acta Informatica Medica, 20 (3), 180-185.
Kokaia, Z., Thored, P., Arvidsson A., & Lindvall, O. (2006). Regulation of stroke-induced neurogenesis in adult brain—recent scientific progress. Cerebral Cortex, 16(Suppl 1), i162-i167.
Li, H., Horke, S., & Förstermann, U. (2013). Oxidative stress in vascular disease and its pharmacological prevention. Trends in Pharmacological Sciences, 34(6), 313-319.
Liu, J-Q., Dai, S-X., Zheng, J-J., Guo, Y-C., Li, W-X., Li, G-H., & Huang, J-F. (2017). The identification and molecular mechanism of anti-stroke traditional Chinese medicinal compounds. Scientific Reports, 7, 14106. 1-11.
Lo, E.H., Moskowitz, M.A., & Jacobs, T.P. (2005). Exciting, radical, suicidal: how brain cells die after stroke. Stroke, 36(2), 189-192.
Longa, E.Z., Weinstein, P.R., Carlson, S., & Cummins, R. (1989).Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 20(1), 84-91.
McCord, J.M. & Fridovich, I. (1969).Superoxide dismutase: an enzymic function for erythrocuprein (hemocuprein). Journal of Biological Chemistry, 244, 6049–6055.
Ministry of public health. (2002). Burden of disease and injuries in Thailand Priority setting for policy, A14-16, 58.
Moskowitz, M.A., Lo, E.H., & Iadecola, C. (2010). The Science of stroke: Mechanisms in search of treatments. Neuron, 67(2), 181-198.
Nimse, S.B., Pal, D. (2015). Free radicals, natural antioxidants, and their reaction mechanisms. RSC Advances,
5(35), 27986-28006.
Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Annals of Biochemistry, 95, 351–358.
Otsuki, N., Dang, N. H., Kumagai, E., Kondo A., Iwata, S., & Morimoto, C. (2010). Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. Journal of Ethnopharmacology, 127(3), 760-767.
Pongmayteegul, S. (2010). Experimental models of global and focal cerebral ischemia. Journal of Medicine and Health Sciences, 17 (3), 149 -159. (in Thai)
Parmeshwar L.S., Ishwar S.S., & Ravish, C. (2015). Papaya: Biology, cultivation, production and uses.
(pp. 169 -188). New York: CRC Press.
Sadek, K.M. (2012). Antioxidant and immunostimulant effect of Carica papaya Linn. aqueous extract in acrylamide intoxicated rats. Acta Informatica Medica, 20(3), 180-185.
Sankat, C.K., & Maharaj, R.P. (1997). In: Mitra SK. (Ed.), Postharvest physiology and storage of tropical and subtropical foods. (pp. 167-189). New York: Cab International.
Sawatdiyapanon, C., & Kaewkaen, P. (2015). Behavioral effect of Carica papaya L. fruits juice in animal model of mild cognitive impairment. In Proceedings of the Burapha University International Conference 2015. (pp. 423-429). Chon Buri: Thailand.
Wang, S., Cu, Y., Wang, C., Xie, W., Ma, L., Zhu, J. (2015). Protective effects of dietary supplementation with a combination of nutrients in a transgenic mouse Mmodel of Alzheimer’s disease. PLoS ONE, 10(11), e0143135.
Wendel, A. (1981). Glutathione peroxidase. Methods in Enzymology, 77, 325-333.
World Health Organization. (2014).Global status report on non-communicable diseases. Geneva: World Health Organization.
Zhou, L., Paull, R.E. (2001). Sucrose metabolism during papaya (Carica papaya L.) fruit growth and ripening. Journal of the American Society for Horticultural Science, 126, 351-357.
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Published
2019-01-16
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