THE EFFECTS OF ETHANOL EXTRACTS OF <i>Centella asiatica</i> LEAF ON SERIAL SERUM BRAIN DERIVED NEUROTROPHIN FACTOR (BDNF) CONCENTRATION OF RATS (SPRAGUE DAWLEY) FOLLOWING CHRONIC STRESS
Abstract
Centella asiatica is considered herbal plant for increasing memory performance. Brain-derived neurotrophin factor (BDNF) has a significant role in memory formation process, while stress causes memory impairment. Objective: This study aimed to investigate the effects of ethanol extracts of Centella asiatica leaf on serum BDNF concentration of rats that was taken serially before and after chronic electrical stress. Materials and Methods : Twenty male rats (Sprague Dawley) were divided into four groups: control/aquades group and groups treated with different doses (mg/kg) of Centella asiatica :150 (CA150), 300 (CA300) and 600 (CA600). Each rat underwent memory exercise for nine days before and after electrical stress and oral administration of ethanol extracts of Centella asiatica for twenty-eight days. Blood sampling was taken serially from rats’ tail for four times : (1) before memory exercise, (2) after memory exercise (before stress), (3) after chronic stress, and (4) after memory exercise (following chronic stress). Concentration of serum BDNF was assessed using ELISA. Results: There was no significant difference in serum BDNF concentration between groups in first and second serum sampling, which was prior to chronic stress and administration of different treatments. However, there was significant difference in third and fourth serum sampling between groups. Mean concentration of serum BDNF (ng/ml) in third and fourth sampling for control group, CA150, CA300, and CA600, respectively were 1.88+0.21 &1.93+0.24; 2.29+0.13 & 2.01+0.22; 2.29+0.08 &1.86+0.11; 2.71+0.70 and 2.99+0.27 (p<0.05). Conclusion: Ethanol extracts of Centella asiatica leaf increases serum BDNF concentration in rats after chronic stress.
Keywords: stress, memory, Centella asiatica, BDNF
References
Astari, A.N., D.C.R. Sari, S. Aswin, and S. Suharmi. 2012. The Effect of Administration Pegagan Ethanolic Extract on the Number of Hippocampal CA3 Pyramidal Neuron: Study on Rats (Rattus norvegicus) post-stress Electricity with dose 300mg/kgBW for 4 weeks and 6 weeks. Proceeding 23rd European Students Conference 17th-20th, Berlin, Germany.
Baran, S.E, A.M. Campbell, J.K. Kleen, C.H. Foltz, R.L. Wright, D.M. Diamond, and C.D. Conrad. 2006. Combination of High Fat Diet and Chronic Stress Retracts Hippocampal Dendrites. Neuroreport 16 (1): 39–43.
Dhanasekaran, M., L.A. Holcomb, A.R. Hitt, B. Tharakan, J.W. Porter, K.A. Young, and B.V. Manyam. 2009. “Centella asiatica Extract Selectively Decreases Amyloid ² Levels in Hippocampus of Alzheimer’s Disease Animal Model. Phytotherapy Research, vol. 19, no. December 2008 :14–19.
Elfving, B., P. H. Plougmann, and G. Wegener. 2010. Detection of Brain-derived Neurotrophic Factor (BDNF) in Rat Blood and Brain Preparations Using ELISA: Pitfalls and Solutions. Journal of Neuroscience Methods 187 (1) (March 15): 73–7.
Fabel, K., B. Tam, D. Kaufer, A. Baiker, N. Simmons, C.J. Kuo, and T.D. Palmer. 2003. VEGF is Necessary for Exercise-Induced Adult Hippocampal Neurogenesis. EurJ Neurosci Nov 18(10):2803-12.
Fang, Z.H., C.H. Lee, M.K. Seo, H. Cho, J.G. Lee, B.J. Lee, S.W. Park, and Y.H. Kim. 2013. Effect of Treadmill Exercise on the BDNF-mediated Pathway in the Hippocampus of Stressed Rats. Neuroscience Research 76 (4) (August): 187–94.
Givalois, L., F. Marmigère, F. Rage, G. Ixart, S. Arancibia, and L. Tapia-Arancibia. 2001. Immobilization Stress Rapidly and Differentially Modulates BDNF and TrkB mRNA Expression in The Pituitary Gland of Adult Male Rats. Neuroendocrinology. Sep;74(3):148-59.
Klein, A.B., R. Williamson, M.A. Santini, C. Clemmensen, A. Ettrup, M. Rios, G.M. Knudsen, and S. Aznar. 2011. Blood BDNF Concentrations Reflect Brain-tissue BDNF Levels Across Species. The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) 14 (3) (April): 347–53.
Kojima, N. 1997. Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene. Proc Natl Acad Sci U S A 94(9): 4761-5.
Krishnamurthy, G. Rajanikant, M-C. Senut, D. Zemke, J. Min, B. Frenkel, E.J. Greenberg, SW. Yu. 2010. Asiatic Acid, a Pentacyclic Triterpene From Centella asiatica Is Neuroprotective in a Mouse Model of Focal Cerebral Ischemia. Journal of Neuroscience Research 87 (11): 2541–2550.
Kumar,A., A. Prakash, and S. Dogra. 2011. Centella asiatica Attenuates D-Galactose-Induced Cognitive Impairment, Oxidative and Mitochondrial Dysfunction in Mice. International journal of Alzheimer’s disease, vol. 2011, p. 347569.
Lambert, K.G., S.K. Buckelew, G. S. Sandoz, S. Gaffga, W. Carpenter, J. Fisher, and C.H. Kinsley. 1998. Activity-stress Induces Atrophy of Apical Dendrites of Hippocampal Pyramidal Neurons in Male Rats. Physiology & Behavior 65 (1) (August): 43–9.
Leibrock, J., F. Lottspeich, A. Hohn, M. Hofer, B. Hengerer, P. Masia-kowski, H. Thoenen, and Y-A. Barde. 1989. Molecular cloning and expression of brain-derived neurotrophic factor. Nature, vol. 341:149-52.
Leuner, B., E. Gould, and T.J. Shors. 2006. Is There a Link Between Adult Neurogenesis and Learning? Hippocampus 16 (3) (January): 216–24.
Li, X-H., N-B. Liu, M-H. Zhang, Y-L. Zhou, J-W. Liao, X-Q. Liu, and H-W. Chen. 2007. Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats. Chinese Medical Journal, vol. 120 (8):669-674.
Liu, N.B. 2004. Chronic multiple stress enhances learning and memory capability in rats. Sheng Li Xue Bao 56(5): 615-9.
Mclaughlin, K.J., J. Gomez, S.E. Baran, and C. D. Conrad. 2009. Function : An Evaluation of Chronic Restraint Paradigms. Brain Research vol.1161:56–64.
Mizuno, M., K. Yamada, J. He, and A. Nakajima. 2003. Involvement of BDNF Receptor TrkB in Spatial Memory Formation. Learning & Memory by Cold Spring Harbor Laboratory Press, vol. 10:108-115.
Mizuno, M., K. Yamada, N. Takei, M.H. Tran, J. He, A. Nakajima, H. Nawa, and T. Nabeshima. 2003. Phosphatidylinositol 3-kinase: a Molecule Mediating BDNF-dependent Spatial Memory Formation. Molecular Psychiatry 8 (2) (March): 217–24.
Mohandas, R.K.G., R.S. Muddanna, and R.S. Gurumadhva. 2006. Centella asiatica (L.) leaf extract treatment during the growth spurt period enhances hippocampal CA3 neuronal dendritic arborization in rats. Evidence-based complementary and alternative medicine: eCAM, vol. 3, no. 3, pp. 349–57, Sep. 2006.
Mohandas, R.K.G., R.S. Muddanna, and R.S. Gurumadhva. 2009. Enhancement of Amygdaloid Neuronal Dendritic Arborization by Fresh Leaf Juice of Centella asiatica (Linn) During Growth Spurt Period in Rats. Evidence-based complementary and alternative medicine : eCAM, vol. 6, no. 2, pp. 203–10, Jun.
Morris, R.G.M., E.I. Moser, G. Riedel, S.J. Martin, J. Sandin, M. Day, and C. O’Carroll. 2003. Elements of a neurobiological theory of the hippocampus: the role of activity-dependent synaptic plasticity in memory. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, vol. 358 (1432) : 773–86.
Nibuya, M., M. Takahashi, D.S. Russell, and R.S. Duman RS. 1999. Repeated Stress Increases Catalytic TrkB mRNA in Rat Hippocampus. Neurosci Lett. May 267(2):81-4.
Pittella, F., R.C. Dutra, D.D Junior, M.T.P. Lopes, and N.R. Barbosa. 2009. Antioxidant and Cytotoxic Activities of Centella asiatica (L) Urb. International Journal of Molecular Sciences 10 (9) (September): 3713–21.
Radak, Z., A. Toldy, Z. Szabo, S. Siamilis, C. Nyakas, G. Silye, J. Jakus, and S. Goto. 2006. The Effects of Training and Detraining on Memory, Neurotrophins and Oxidative Stress Markers in Rat Brain. Neurochemistry International 49 (4) (September): 387–92.
Radák, Z., T. Kaneko, S. Tahara, H. Nakamoto, J. Pucsok, M. Sasvári, C. Nyakas, and S. Goto. 2001. Regular exercise improves cognitive function and decreases oxidative damage in rat brain. Neurochem Int. Jan;38(1):17-23.
Rage, F., L. Givalois, F. Marmigère, L. Tapia-Arancibia, and S. Arancibia. 2002. Immobilization Stress Rapidly Modulates BDNF mRNA Expression in the Hypothalamus of Adult Male Rats. Neuroscience.112(2):309-18.
Sari, D.C.R. 2011.The Relationship between Memory, CA1 Hippocampus and Neuroglia after Centella asiatica Leaf Extract’s Administration in Stress-Induced Rat (Rattus norvegicus). Proceeding of International Joint Symposium. Frontier in Biomedical Sciences: from Genes to Applications. Faculty of Medicine, UGM, Yogyakarta, Indonesia. Nov. 2011.
Sari, D.C.R., and M. Ar-Rochmah. 2012. The Effect of Ethanol Extracts of Centella Asiatica Leaf on the Retention of Spatial Memory in Rats (Sprague-dawley) after chronic electrical stress. Buku Panduan dan Kumpulan Abstract Pertemuan Ilmiah Nasional Perhimpunan Ahli Anatomi Indonesia XIV Komisariat PAAI Denpasar. Oct 2012.
Sari, D.C.R., R.S. Pratama, S. Aswin, and S. Suharmi. 2011.The effect of Centella asiatica ethanolic extract’s administration duration on spatial memory in rat (Rattus norvegicus) after electric- stress induced. Jurnal kedokteran kesehatan mutiara medika UMY. Mutiara Medika Journal Kedokteran Kesehatan, vol. 11 (3).
Sari, D.C.R., S. Aswin, S. Suharmi, M. Romi, and U. Tranggono. 2012. The relationship between Spatial Memory and the Thickness of Hippocampal CA1 Pyramidal Layer in Stress-induced Rats (Rattus norvegicus) after Centella asiatica Leaf Extract’s Administration. Nutrition & Dietetics Journal of the Dietitians Association of Australia, including the Journal of Dietitians New Zealand. Vol 69. Supl. 1. Sept 2012.
Shi, S-S., S-H. Shao, B-P. Yuan, F. Pan, and Z-L. Li. 2010. Acute Stress and Chronic Stress Change Brain-derived Neurotrophic Factor (BDNF) and Tyrosine Kinase-coupled Receptor (TrkB) Expression in Both Young and Aged Rat Hippocampus. Yonsei Medical Journal 51 (5) (September): 661–71.
Sousa, N., N. Lukoyanov, Md Madeira of Almeida, and M. Paula-Barbosa. 2000. Erratum to Reorganization of the Morphology of Hippocampal Neurites and Synapses After Stress-induced Damage Correlates with Behavioral Improvement. Neuroscience 101 (2) (January): 483.
Sun, C.Y. 2006. Changes of learning, memory and levels of CaMKII, CaM mRNA, CREB mRNA in the hippocampus of chronic multiple-stressed rats. Chin Med J (Engl), 119(2): 140-7.
Terry, A.V. 2009. Chapter 13 : Spatial Navigation (Water Maze) Tasks. Methods of Behavior Analysis in Neuroscience 2nd edition. Boca Raton (FL) CRC Press.
Trentani, A., S.D. Kuipers, G.J. Ter Horst, and J.A. Den Boer. 2002. Selective Chronic Stress-induced in Vivo ERK1/2 Hyperphosphorylation in Medial Prefrontocortical Dendrites: Implications for Stress-related Cortical Pathology?. European Journal of Neuroscience 15 (10) (May): 1681–1691.
Venero, C, T. Tilling, I. Hermans-Borgmeyer, R .Schmidt, M. Schachner, and C. Sandi. 2002. Chronic Stress Induces Opposite Changes in the mRNA Expression of the Cell Adhesion Molecules NCAM and L1. Neuroscience 115 (4) (January): 1211–9.
Yamada, K., M. Mizuno, and T. Nabeshima. 2002. Role for Brain-derived Neurotrophic Factor in Learning and Memory. Life Sciences 70 (7) (January 4): 735–44.
Zheng, C., and L. Qin. 2007. Chemicalcomponentsof Centellaasiatica andtheirbioactivities. Journal of Chinese Integrative Medicine, vol. 5:348-351.