Ethanolic extract of the Centella asiatica (L.) Urb. leaf decreases cerebellar brain-derived neurotrophic factor (BDNF) levels in rats after chronic stress

https://doi.org/10.19106/JMedSci005002201801

Dwi Cahyani Ratna Sari(1*), Desby Juananda(2), Mawaddah Ar-Rochmah(3), Muhammad Mansyur Romi(4), Nur Arfian(5)

(1) Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta,
(2) Department of Anatomy, Faculty of Medicine, Riau University, Pekanbaru, Indonesia
(3) Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta,
(4) Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta,
(5) Department of Anatomy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta,
(*) Corresponding Author

Abstract


Chronic stress produces glucocorticoid-induced neurotoxicity that may lead to alterations of the brain-derived neurotrophic factor (BDNF) concentration in the brain. Cerebellum is known to be severely affected by glucocorticoids-associated oxidative damage. Centella asiatica (L.) Urb. may protect neurons from oxidative damage. This study aimed to investigate the effect of ethanolic extract of C. asiatica (L.) Urb. leaf on the rat cerebellar BDNF levels following stress. Twenty young-adult male Sprague Dawley rats were randomly assigned into four experimental groups. The stress control group received aquadest, and the other groups were treated with different doses of the C. asiatica (L.) Urb. extract i.e 150 (CeA150), 300 (CeA300) and 600 (CeA600) mg/kg body weight/day orally, respectively and followed by chronic footshock stress for 28 days. Upon completion of the experimental period, all animals were sacrificed and the cerebellar was isolated. The BDNF levels from the cerebellar tissue lysate was measured using ELISA. The mean BDNF levels of the cerebellar tissue in the stress control, CeA150, CeA300 and CeA600 groups were 1217.10±301.40; 771.46±241.45; 757.05±268.29; and 627.00±246.02 pg/mL, respectively. Post-hoc analysis showed a significant difference between the control and treatment groups (p< 0.05). In conclusion, the ethanolic extracts of the C. asiatica (L.) Urb. leaf decrease the cerebellar BDNF levels in rats after chronic stress.

Keywords


BDNF - Centella asiatica (L.) Urb. - cerebellum - chronic stress - prevention

Full Text:

PDF


References

Gohil KJ, Patel JA, Gajj AK. Pharmacological Review on Centella asiatica: A Potential Herbal Cure-all. Indian J Pharm Sci. 2010;Sept-Oct 7(5):546–56. 2. Seevaratnam V, Banumathi P, Premalatha M., Sundaram S, Arumugam T. Functional Properties of Centella Asiatica (L.): A Review. Int J Pharm Pharm Sci. 2012;4:8–14. 3. Krishnamurthy RG, Senut M, Zemke D, Min J, Frenkel MB, Greenberg EJ, et al. Asiatic Acid , a Pentacyclic Triterpene From Centella asiatica , Is Neuroprotective in a Mouse Model of Focal Cerebral Ischemia. J Neurosci Res. 2009;2550:2541–50. 4. Sari DCR, Aswin S, Susilowati R, Ar-rochmah M, Prakosa D, Tranggono U, et al. Ethanol Extracts of Centella asiatica Leaf Improves Memory Performance in Rats after Chronic Stress via Reducing Nitric Oxide and Increasing Brain- Derived Neurotrophic Factor ( BDNF ) Concentration. Int J Psychol. 2014;1(1):61–7. 5. Sari DCR, Ar Rochmah M. The effects of Ethanol Extracts of Centella asiatica Leaf on Serial Serum Brain-Derived Neurotrophin Factor (BDNF) Concentration of Rats (Sprague Dawley) Following Chronic Stress. Conference, International Science Biological. 2015. p. 159–67. 6. Popoli M, Yan Z, Mcewen BS, Sanacora G. The stressed synapse : the impact of stress and glucocorticoids on glutamate transmission. Neuroscience. 2012;13(November):22–37. 7. Radley JJ, Morrison JH. Repeated stress and structural plasticity in the brain. Ageing Research Reviews. 2005;4:271–87. 8. Joels M. Chronic stress : Implications for neuronal morphology , function and neurogenesis Chronic stress : Implications for neuronal morphology, function and neurogenesis. Neuroendocrinology. 2007;28(August):72-96 9. Zafir A, Banu N. Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. 2009;12(March):167–77. 10. Biran V, Verney C, Ferriero DM. Perinatal Cerebellar Injury in Human and Animal Models. Neurology Research International. 2012 11. Assunção M, Santos-marques MJ, Freitas V De, Paula-barbosa MM, Carvalho F. Modulation of rat cerebellum oxidative status by prolonged red wine consumption. 2008;337–44. 12. Kitraki E, Karandrea D, Kittas C. Long-lasting effects of stress on glucocorticoid receptor gene expression in the rat brain. Neuroendocrinology. 1999;69(5):331–8. 13. Numakawa T, Matsumoto T, Numakawa Y, Richards M, Yamawaki S, Kunugi H. Protective Action of Neurotrophic Factors and Estrogen against Oxidative Stress-Mediated Neurodegeneration. J Toxicology. 2011. 14. Schwartz PM, Borghesani PR, Levy RL, Pomeroy SL, Segal RA. Abnormal Cerebellar Development and Foliation in BDNF -/- Mice Reveals a Role for Neurotrophins in CNS Patterning. Neuron. 1997;19:269–81. 15. Sun X, Zhou H, Luo X, Li S, Yu D, Hua J, et al. Neuroprotection of brain-derived neurotrophic factor against hypoxic injury in vitro requires activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. Int. J. Devl Neuroscience. 2008;26:363–70. 16. Suri D, Vaidya VA. Glucocorticoid Regulation of Brain-Derived Neurotrophic Factor : Relevance to Hippocampal Structural and Functional Plasticity. Neuroscience. 2012. 17. Shi S, Shao S, Yuan B, Pan F, Li Z. 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 Med J. 2010;51(5):661–71. 18. Li XH, Liu NB, Zhang MH, Zhou YL, Liao JW, Liu XQ CH. Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats. Chin Med J (Engl). 2007;120(8):669–74. 19. Larsen MH, Mikkelsen JD, Hay-schmidt A, Sandi C. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment. J Psychiatr Res. 2010;44(13):808–16. 20. Allen SJ, Dawbarn D. Clinical relevance of the neurotrophins and their receptors. Clin Sci. 2006;110, 175–191. 21. Torres SJ, Diet MN, Nowson CA, Ph D. Relationship between stress, eating behavior, and obesity. Nutrition. 2007;23:887–94. 22. Bazhan N, Zelena D. Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis. Brain Res Bull; 2013;95:46–53. 23. Maniam J, Morris MJ. Neuropharmacology The link between stress and feeding behaviour. Neuropharmacology. 2012;63(1):97–110. 24. Mayer EA, Naliboff BD, Lin C, Coutinho S V. Stress and the Gastrointestinal Tract V. Stress and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2001;280:G519–24. 25. Taché Y, Bonaz B. Review series Corticotropin-releasing factor receptors and stress-related alterations of gut motor function. J Clin Invest. 2007;117(1):33–40. 26. Miyata K, Ito H, Fukudo S. Involvement of the 5-HT 3 receptor in CRH-induced defecation in rats. Am Physiol Soc. 1998;827–31. 27. Sanger GJ, Yoshida M, Yahyah M, Kitazumi K. Increased defecation during stress or after 5-hydroxytryptophan : selective inhibition by the 5-HT 4 receptor antagonist. British Journal of Pharmacology. 2000;706–12. 28. Miki T, Yokoyama T, Kusaka T, Suzuki S, Ohta K, Warita K, et al. Early postnatal repeated maternal deprivation causes a transient increase in OMpg and BDNF in rat cerebellum suggesting precocious myelination. J Neurol Sci; 2014;336(1-2):62–7. 29. Banerjee R, Ghosh AK, Ghosh B, Mondal AC. Effect of Chronic Inescapable Footshock and Antidepressant Treatment on BDNF/TrkB Levels in Rat Hippocampus. J Neurosci. 2012;2(2):12–21. 30. Grønli J, Bramham C, Murison R, Kanhema T, Fiske E. Chronic mild stress inhibits BDNF protein expression and CREB activation in the dentate gyrus but not in the hippocampus proper. Pharmacol Biochem Behav. 2007;85(2006):842–9. 31. Kumar A, Lavoie HA, Dipette DJ, Singh US. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications. Brain Sci. 2013;1:941–63. 32. Kloet ER De, Joëls M, Holsboer F. Stress and The Brain : From Adaptation to Disease. Neurosci. 2005;6(June):463–75. 33. Chen AI, Xiong L, Tong YU, Mao M. The neuroprotective roles of BDNF in hypoxic ischemic brain injury ( Review ). Biomed Rep. 2013;167–76. 34. Marosi K, Mattson MP. BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab. 2013;1–10. 35. Batchelor PE, Liberatore GT, Wong JYF, Porritt MJ, Frerichs F, Donnan GA, et al. Activated Macrophages and Microglia Induce Dopaminergic Sprouting in the Injured Striatum and Express Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor. J Neurosci. 1999;19(5):1708–16. 36. Orhan IE. Centella asiatica ( L .) Urban : From Traditional Medicine to Modern Medicine with Neuroprotective Potential. J Evid Based Complementary Altern Med. 2012;2012. 37. Subathra M, Shila S, Devi MA, Panneerselvam C. Emerging role of Centella asiatica in improving age-related neurological antioxidant status. Exp. Gerontol. 2005;40:707–15. 38. Wijeweera P, Arnason JT, Koszycki D, Merali Z. Evaluation of anxiolytic properties of Gotukola– (Centella asiatica) extracts and asiaticoside in rat behavioral models. Phytomedicine. 2006;13:668–76. 39. Liang X, Huang YN, Chen SW, Wang WJ, Xu N, Cui S, et al. Antidepressant-like effect of asiaticoside in mice. Pharmacol Biochem Behav. 2008;89:444–9. 40. Rao MS. Anti stress effect of Centella asiatica leaf extract on hippocampal CA3 neurons – a quantitative study. Int J Pharmacoland ClinSci. 2013;2(1):25–32. 41. Schutter DJLG, Honk JVAN. The cerebellum on the rise in human emotion. The Cerebellum. 2005;(April):290–4.



DOI: https://doi.org/10.19106/JMedSci005002201801

Article Metrics

Abstract views : 2388 | views : 2381


Bookmark and Share


Copyright (c) 2018 Dwi Cahyani Ratna Sari, Desby Juananda, Mawaddah Ar-Rochmah, Muhammad Mansyur Romi, Nur Arfian

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.