Centella asiatica increases B-cell lymphoma 2 expression in rat prefrontal cortex

Main Article Content

Kuswati Kuswati
Djoko Prakosa
Brian Wasita
Nanang Wiyono


Stress is one of the factors that cause apoptosis in neuronal cells. Centella
asiatica has a neuroprotective effect that can inhibit apoptosis. This study
aimed to examine the effect of Centella asiatica ethanol extract on B-cell
lymphoma 2 (Bcl-2) protein expression in the prefrontal cortex of rats.

An experimental study was conducted on 34 brain tissue samples from male
Sprague Dawley rats exposed to chronic restraint stress for 21 days. The
samples were taken from following groups: non-stress group K, negative
control group P1 (stress + arabic gum powder), P2 (stress + C.asiatica at
150 mg/kgBW), P3 (stress + C.asiatica at 300 mg/kg BW), P4 (stress +
C.asiatica at 600 mg/kg body weight) and positive control group P5 (stress
+ fluoxetine at 10 mg/kgBW). The samples were made into sections that
were stained immunohistochemically using Bcl-2 antibody to determine the
percentage of cells expressing Bcl-2. Data were analyzed using one way
ANOVA test followed by a post - hoc test.

There were significant differences in mean Bcl-2 expression between the
groups receiving Centella asiatica compared with the non-stress group and
stress-only group (negative control group) (p<0.05). The results were
comparable to those of the fluoxetine treatment group.


The Centella asiatica ethanol extract was able to increase Bcl-2 expression
in the prefrontal cortex of Sprague Dawley rats exposed to restraint stress.
This study suggests that Centella asiatica may be useful in the treatment of
cerebral stress.

Article Details

How to Cite
Kuswati, K., Prakosa, D., Wasita, B., & Wiyono, N. (2015). Centella asiatica increases B-cell lymphoma 2 expression in rat prefrontal cortex. Universa Medicina, 34(1), 10–16. https://doi.org/10.18051/UnivMed.2015.v34.10-16
Review Article
Author Biographies

Kuswati Kuswati, Department of Anatomy, Faculty of Medicine, Islamic University of Indonesia

Department of Anatomy,

Djoko Prakosa, Department of Anatomy, Embryology and Anthropology, Faculty of Medicine Gadjah Mada University

Department of Anatomy,

Brian Wasita, Department of Pathological Anatomy, Faculty of Medicine, Sebelas Maret University

Department of Pathological

Nanang Wiyono, Department of Anatomy, Faculty of Medicine, Sebelas Maret University

Department of Anatomy,
Faculty of Medicine,
Sebelas Maret University


Chen SD, Yang DI, Lin TK, et al. Roles of oxidative stress, apoptosis, PGC-1α and mitochondrial biogenesis in cerebral ischemia. Int J Mol Sci 2011;12:7199-215.

Wilber AA, Walker AG, Southwood CJ, et al.Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction Neuroscience 2011;174:115–31.

Goldwater DS, Pavlides CP, Hunter RG, et al. Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery. Neuroscience 2009;164:798–808.

Murray F, Hutson PH. Hippocampal Bcl-2 expression is selectively increased following chronic but not acute treatment with antidepressants, 5-HT1A or 5-HT2C/2B receptor antagonists. Eur J Pharmacol 2007;569: 41–7.

Shiskina GT, Kalinina TS, Berezova IV, et al. Stress-induced activation of the brainstem Bclxl gene expression in rats treated with fluoxetine:correlation with serotonin metabolism and

depressive-like behavior. Neuropharmacology 2012;62:177-83.

Ferguson JM. SSRI antidepressant medications:adverse effects and tolerability. J Clin Psychiatry 2001;3:22-7.

Chauhan PK, Singh V. Acute and subacute toxicity study of the aceton leaf extract of Centella asiatica in experimental animal

models. Asian Pac J Trop Bio 2012;2:511-3.

Kumar A, Dogra S, Prakash A. Neuroprotective effects of Centella asiatica against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress. Int J

Alzheimer Dis 2009. Article ID 972178, 8 pages, doi:10.4061/2009/972178.

Sari DCR. The relationship between memory,CA1 hippocampus and neuroglia after Centella asiatica leaf extract’s administration in stressinduced rat (Rattus norvegicus), Proceeding of 2nd International Joint Symposium Frontier In Biomedical Sciences: From Genes to Applications Faculty of Medicine Gadjah Mada

University. Yogyakarta;2011.

Sari DCR, Aswin S, Suharmi S, et al. The effect of Centella asiatica ethanolic extract’s administration duration on spatial memory in rat (Rattus norvegicus) after electric-stress

induced. Mutiara Medika Jurnal Kedokteran Kesehatan 2011;3:1-10.

Charan J, Kantharia ND. How to calculate sample size in animal studies? J Pharmacol Pharmacother 2013;4:303–6. doi: 10.4103/0976-500X.119726

Paxinos G, Watson C. The rat brain. 6th ed. Philadelphia: Elsevier Inc.;2007.p.11-8.

Kim BK, Ko IG, Kim SE, et al. Impact of several types of stresses on short-term memory and apoptosis in the hippocampus of rats. Int Neurourol J 2013;17:114-20.

Tan ML, Ooi JP, Ismail N, et al. Programmed cell death pathways and current antitumor targets. Pharm Res 2009;26;7:1547-56.

Uvarajan S, Janardhanam VA, Gopinath G. Neuro-shielding effect of asiaticoside against MPTP induced variations in experimental mice. IJEST 2012;4:960-5.

Orhan IE. Centella asiatica (L.) Urban: from traditional medicine to modern medicine with neuroprotective potential. Evid Based Complement Alternat Med 2012;10:1-8.

Kosten, TA, Galloway MP, Duman RS, et al. Repeated unpredictable stress and antidepressants differentially regulate expression of the Bcl-2 family of apoptotic genes in rat

cortical, hippocampal and limbic brain structures. Neuropsychopharmacology 2008;33:1545-58.

Guirado R, Matarredona DS, Varea E, et al. Chronic fluoxetine treatment in middle aged rats induces changes in the expression of plasticity related molecules and in neurogenesis. BMC

Neurosci 2012;5:1-13.

Huang GJ, Herbert J. Stimulation of neurogenesis in the hippocampus of the adult rat by fluoxetine requires rhythmic change in corticosterone. Biological Psychiatry 2006;59:619-24.