Effects of Centella asiatica L. On Spatial Memory and Bcl-2 Gene Expression in the Hippocampus of Rats Injected With Trimethyltin
Keywords:
Centella asiatica, Bcl-2, spatial memory, trimethyltin
Abstract
Cell death (apoptosis) in the hippocampus is related to impaired memory functions. Gotu kola (Centella asiatica) contains asiatic acid and asiaticoside, which act as antioxidants and improve memory function. This study was intended to determine the effects of gotu kola extracts on Bcl-2 gene expression and spatial memory in rats with impaired memory functions due to trimethyltin (TMT) injection. The rats were subdivided into six groups, each group consisting of 10. The normal group was given sodium carboxymethyl cellulose (CMC-Na); the TMT group was given CMC-Na; the positive group was given 200 mg/kg bw citicoline; the extract groups were given a variation of gotu kola extract at 100 (P100), 200 (P200), and 400 mg/kg bw (P400) doses, respectively. These treatments were conducted for 35 days. TMT was injected intraperitoneally on Day 8 of treatment at a dose of 8 mg/kg bw in all groups except the normal group. On Days 29-35, the Morris water maze (MWM) spatial memory test was conducted. The rats were sacrificed, and their hippocampi were taken for immunohistochemical observation of Bcl-2 gene expression. The results showed TMT injection could lower the spatial memory of rats in the MWM and cause apoptosis of the pyramidal cells of the hippocampus. Gotu kola extract at 100, 200 and 400 mg/kg bw could increase the percentage of time spent (duration) and frequency of rats staying in the target quadrant in the probe trial of the MWM and increase Bcl-2 gene expression in the pyramidal cells of the hippocampus. Overall, the results have confirmed that gotu kola extract has the potential to prevent hippocampal cell death and improve the spatial memory of rats injected by TMT.
References
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Furukawa, S., Hattori, N., Ohta, S., Sakamoto, T., & Mishima, S. (2011). Royal jelly facilitates restoration of the cognitive ability in trimethyltin-intoxicated mice. Evidence-Based Complementary and Alternative Medicine, 2011. https://doi.org/10.1093/ecam/nep029
Geloso, M. C., Corvino, V., & Michetti, F. (2011). Trimethyltin-induced hippocampal degeneration as a tool to investigate neurodegenerative processes. Neurochemistry International, 58(7), 729–738. https://doi.org/10.1016/j.neuint.2011.03.009
Geloso, M. C., Vercelli, A., Corvino, V., Repici, M., Boca, M., Haglid, K., … Michetti, F. (2002). Cyclooxygenase-2 and caspase 3 expression in trimethyltin-induced apoptosis in the mouse hippocampus. Experimental Neurology, 175(1), 152–160. https://doi.org/10.1006/exnr.2002.7866
Irham, W. H., Tamrin, Marpaung, L., & Marpongahtun. (2019). Bioactive Compounds in Pegagan Leaf (Centella asiatica L. Urban) for Wound Healing. Journal of Physics: Conference Series, 1232(1), 5–10. https://doi.org/10.1088/1742-6596/1232/1/012019
JE, H. G. and H. (2011). textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Jenkins, S. M., & Barone, S. (2004). The neurotoxicant trimethyltin induces apoptosis via caspase activation, p38 protein kinase, and oxidative stress in PC12 cells. Toxicology Letters, 147(1), 63–72. https://doi.org/10.1016/j.toxlet.2003.10.023
Kang, J. Y., Park, S. K., Guo, T. J., Ha, J. S., Lee, D. S., Kim, J. M., … Heo, H. J. (2016). Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid. Oxidative Medicine and Cellular Longevity, 2016. https://doi.org/10.1155/2016/6981595
Kassed, C. A., Butler, T. L., Navidomskis, M. T., Gordon, M. N., Morgan, D., & Pennypacker, K. R. (2003). Mice expressing human mutant presenilin-1 exhibit decreased activation of NF-κB p50 in hippocampal neurons after injury. Molecular Brain Research, 110(1), 152–157. https://doi.org/10.1016/S0169-328X(02)00658-7
Kesner, R. P., & Hunsaker, M. R. (2010). The temporal attributes of episodic memory. Behavioural Brain Research, 215(2), 299–309. https://doi.org/10.1016/j.bbr.2009.12.029
Kim S.R., Koo K.A., Lee M.K., Park H.G., Jew S.S., Cha K.H., K. Y. C. (2004). Asiatic acid derivatives enhance cognitive performance partly by improving acetylcholine synthesis. J. Pharm. Pharmacol, 56:1275 –.
Lee, K. Y., Bae, O. N., Weinstock, S., Kassab, M., & Majid, A. (2014). Neuroprotective effect of asiatic acid in rat model of focal embolic stroke. Biological and Pharmaceutical Bulletin, 37(8), 1397–1401. https://doi.org/10.1248/bpb.b14-00055
Lee M.K., Kim S.R., Sung S.H., Lim D., Kim H., Choi H., Park H.K., Je S., K. Y. C. (2000). Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity. Res. Commun. Mol. Pathol. Pharmacol, 108:75 – 8.
Lee, S., Yang, M., Kim, J., Kang, S., Kim, J., Kim, J. C., … Moon, C. (2016). Trimethyltin-induced hippocampal neurodegeneration: A mechanism-based review. Brain Research Bulletin, 125, 187–199. https://doi.org/10.1016/j.brainresbull.2016.07.010
Nasir, M. N., Habsah, M., Zamzuri, I., Rammes, G., Hasnan, J., & Abdullah, J. (2011). Effects of asiatic acid on passive and active avoidance task in male Spraque-Dawley rats. Journal of Ethnopharmacology, 134(2), 203–209. https://doi.org/10.1016/j.jep.2010.12.010
Park, H.-J., Shim, H. S., Choi, W. K., Kim, K. S., Bae, H., & Shim, I. (2011). Neuroprotective Effect of Lucium chinense Fruit on Trimethyltin-Induced Learning and Memory Deficits in the Rats. Experimental Neurobiology, 20(3), 137–143. https://doi.org/10.5607/en.2011.20.3.137
Ploughman, M. (2008). Exercise is brain food: The effects of physical activity on cognitive function. Developmental Neurorehabilitation, 11(3), 236–240. https://doi.org/10.1080/17518420801997007
Purves, D., Augustine, G.J., Fitzpatrick, D., Hall, W.C., LaMantia, A., McNamara, J. O. (2004). Neuroscience. 3rd ed. Sinauer Associates Inc. Sunderland. Massachusetts.
Rather, M. A., Thenmozhi, A. J., Manivasagam, T., Bharathi, M. D., Essa, M. M., & Guillemin, G. J. (2018). Neuroprotective role of asiatic acid in aluminium chloride induced rat model of Alzheimer’s disease. Frontiers in Bioscience - Scholar, 10(2), 262–275. https://doi.org/10.2741/s514
Saver, J. L. (2008). Citicoline: Update on a promising and widely available agent for neuroprotection and neurorepair. Reviews in Neurological Diseases, 5(4), 167–177.
Shuto, M., Higuchi, K., Sugiyama, C., Yoneyama, M., Kuramoto, N., Nagashima, R., … Ogita, K. (2009). Endogenous and Exogenous Glucocorticoids Prevent Trimethyltin From Causing Neuronal Degeneration of the Mouse Brain In Vivo: Involvement of Oxidative Stress Pathways. Journal of Pharmacological Sciences, 110(4), 424–436. https://doi.org/10.1254/jphs.09107FP
Sobrado, M., López, M. G., Carceller, F., García, A. G., & Roda, J. M. (2003). Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase Bcl-2 expression after focal cerebral ischemia. Neuroscience, 118(1), 107–113. https://doi.org/10.1016/S0306-4522(02)00912-0
Suparno, S. (2008). Pengaruh stresor fisik terhadap distribusi SERT dan indeks apoptosis neuron hipokampus, serta distribusi TNF-± gaster tikus dengan mediasi kortisol dan IL-6. Journal of Biological Researches, 14(1), 79–90. https://doi.org/10.23869/bphjbr.14.1.200811
Takasaki, K., Uchida, K., Fujikawa, R., Nogami, A., Nakamura, K., Kawasaki, C., … Iwasaki, K. (2011). Neuroprotective effects of citidine-5-diphosphocholine on impaired spatial memory in a rat model of cerebrovascular dementia. Journal of Pharmacological Sciences, 116(2), 232–237. https://doi.org/10.1254/jphs.11013FP
Terry Jr, A. V. (2009). Spatial navigation (water maze) tasks. Methods of Behavior Analysis in Neuroscience, 2.
Uygur, E., & Arslan, M. (2010). Effects of chronic stress on cognitive functions and anxiety related behaviors in rats. Acta Physiologica Hungarica, 97(3), 297–306. https://doi.org/10.1556/APhysiol.97.2010.3.6
Viviani, B., Corsini, E., Pesenti, M., Galli, C. L., & Marinovich, M. (2001). Trimethyltin-activated cyclooxygenase stimulates tumor necrosis factor-α release from glial cells through reactive oxygen species. Toxicology and Applied Pharmacology, 172(2), 93–97. https://doi.org/10.1006/taap.2001.9136
Vorhees, C. V., & Williams, M. T. (2006). Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nature Protocols, 1(2), 848–858. https://doi.org/10.1038/nprot.2006.116
Wang, X., Cai, J., Zhang, J., Wang, C., Yu, A., Chen, Y., & Zuo, Z. (2008). Acute trimethyltin exposure induces oxidative stress response and neuronal apoptosis in Sebastiscus marmoratus. Aquatic Toxicology, 90(1), 58–64. https://doi.org/10.1016/j.aquatox.2008.07.017
Xing Lin 1, Renbin Huang, Shijun Zhang, Ling Wei, Lang Zhuo, Xiaoyan Wu, Aicun Tang, Q. H. (2013). fitoterapia.
Xu, M. F., Xiong, Y. Y., Liu, J. K., Qian, J. J., Zhu, L., & Gao, J. (2012). Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells. Acta Pharmacologica Sinica, 33(5), 578–587. https://doi.org/10.1038/aps.2012.3
Yoon, J., & Gores, G. J. (2002).
Youle, R. J., & Strasser, A. (2008). The BCL-2 protein family: Opposing activities that mediate cell death. Nature Reviews Molecular Cell Biology, 9(1), 47–59. https://doi.org/10.1038/nrm2308
Yuliani, S., & Linar, N. (2019). Effect of Gotu Kola (Centella asiatica) Extract Toward Expression of Caspase 3 of Hippocampus Pyramidal Cells on Dementia Model Rats Induced by Trimethyltin. https://doi.org/10.2991/adics-phs-19.2019.12
Yuliani, S., Mustofa, & Partadiredja, G. (2018). Turmeric (Curcuma longa L.) extract may prevent the deterioration of spatial memory and the deficit of estimated total number of hippocampal pyramidal cells of trimethyltin-exposed rats. Drug and Chemical Toxicology, 41(1), 62–71. https://doi.org/10.1080/01480545.2017.1293087
Zhang, L., Li, L., Prabhakaran, K., Borowitz, J. L., & Isom, G. E. (2006). Trimethyltin-induced apoptosis is associated with upregulation of inducible nitric oxide synthase and Bax in a hippocampal cell line. Toxicology and Applied Pharmacology, 216(1), 34–43. https://doi.org/10.1016/j.taap.2006.05.004
Zhang, Z., Li, X., Li, D., Luo, M., Li, Y., Song, L., & Jiang, X. (2017). Asiaticoside ameliorates β-amyloid-induced learning and memory deficits in rats by inhibiting mitochondrial apoptosis and reducing inflammatory factors. Experimental and Therapeutic Medicine, 13(2), 413–420. https://doi.org/10.3892/etm.2016.4004
Zhao, Y., Shu, P., Zhang, Y., Lin, L., Zhou, H., Xu, Z., … Jin, X. (2014). Effect of centella asiatica on oxidative stress and lipid metabolism in hyperlipidemic animal models. Oxidative Medicine and Cellular Longevity, 2014. https://doi.org/10.1155/2014/154295
Published
2021-06-25
How to Cite
Yuliani, S., Akbar, M. F., Rochmafihro, N., Uthary, Y., & Deslaila, L. (2021). Effects of Centella asiatica L. On Spatial Memory and Bcl-2 Gene Expression in the Hippocampus of Rats Injected With Trimethyltin. Indonesian Journal of Pharmacy, 32(2), 141-149. https://doi.org/10.22146/ijp.1134
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