Assessing the Immunomodulatory Activity of Ethanol Extract of Sambucus javanica Berries and Leaves in Chloramphenicol-Induced Aplastic Anemia Mouse Model
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Abstract
Aplastic anemia, life-threatened disease, is a hematologic disorder characterised by bone marrow hypoplasia. Multiple modalities such as bone marrow transplantation and immunosuppression treatment have been proposed to ameliorate this entity, however it remains ineffective. Sambucus, a group of herb plants, possesses a broad spectrum of medicinal properties such as antioxidant, insulin-like activity, anticancer and antiviral. However, the study about its activity toward aplastic anemia incidence is based on limited data. Thus, the research aim of this study was to evaluate the immunomodulatory activities of Sambucus javanica in chloramphenicol-induced anemia aplastic mouse model. In this present study, BALB/c mice were administrated with chloramphenicol (CMP) to induce aplastic anemia then followed by S. javanica extracts treatment. Additionally, cellular and molecular aspects were evaluated by flow cytometry and Hematoxylin-Eosin staining. Further analysis showed that S. javanica extracts could promote the population number of regulatory T-cells and naïve cytotoxic T-cells. Moreover, those extract also reduced the inflammation and necrotic incidence in CMP-induced mouse aplastic anemia model. Together, these results suggest that S. javanica has therapeutically effect to aplastic anemia by altering the immune system as an immunomodulatory agent.
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References
Abood W N. (2017). Immmunomodulatory and natural immunomodulators. Journal of Allergy and Inflammation 1(2): 1–4.
Atkinson M D and Atkinson E. (2002). Sambucus nigra L. Journal of Ecology 90: 895–923. https://doi.org/10.1046/j.1365-2745.2002.00698.x.
Badescu M, Badulescu O, Badescu L and Ciocoiu M. (2015). Effects of Sambucus nigra and Aronia melanocarpa extracts on immune system disorders within diabetes mellitus. Pharmaceutical Biology 53(4): 533–539. https://doi.org/10.3109/13880209.2014.931441.
Barak V, Birkenfeld S, Halperin T and Kalickman I. (2002). The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines. The Israel Medical Association Journal 4(11): 919–922.
Barsett H, Aslaksen T H, Gildhyal P, Michaelsen T E and Paulsen B S. (2012). Comparison of carbohydrate structures and immunomodulating properties of extracts from berries and flowers of Sambucus nigra L. European Journal of Medicinal Plants 2(3): 216–229. https://doi.org/10.9734/EJMP/2012/1335
Brenner G M and Stevens C W. (2018). Brenner and Stevens’ pharmacology, 5E: drug development and safety. Philadelphia, USA: Elsevier.
Chen J and Liu X. (2009). The role of interferon gamma in regulation of CD4+ T-cells and its clinical implications. Cellular Immunology 254(2): 85–90. https://doi.org/10.1016/j.cellimm.2008.09.001
De Oliveira C B, Comunello L N, Maciel E S, Giubel S R, Bruno A N, Chiela E C F, Lenz G, Gnoatto S C B, Buffon A and Gosmann G. (2013). The inhibitory effects of phenolic and terpenoid compounds from Baccharis trimera in Siha cells: Differences in their activity and mechanism of action. Molecules 18: 11022–11032. https://doi.org/10.3390/molecules180911022
Du D, Jin T, Zhang R, Hu L, Xing Z, Shi N, Shen Y and Gong M. (2017). Phenolic compounds isolated from Dioscorea zingiberensis protect against pancreatic acinar cells necrosis induced by sodium taurocholate. Bioorganic & Medicinal Chemistry Letters 27(6): 1467–1470. https://doi.org/10.1016/j.bmcl.2017.01.014
Durga M, Nathiya S and Devasena T. (2014). Immunomodulatory and antioxidant actions of dietary flavonoids. International Journal of Pharmacy and Pharmaceutical Sciences 6(2): 50–56.
G?man A, G?man G and Bold A. (2009). Acquired aplastic anemia: Correlation between etiology, pathophysiology, bone marrow histology and prognosis factors. Romanian Journal of Morphology and Embryology 50(4): 669–674.
Gorchakova T V, Suprun I V, Sobenin I A and Orekhov A N. (2007). Use of natural products in anticytokine therapy. Bulletin of Experimental Biology and Medicine 143: 316– 319. https://doi.org/10.1007/s10517-007-0099-6
Groza M, Ciocoiu M, B?descu L, B?dulescu O and B?descu M. (2010). The effects of the Sambucus nigra vegetal extracts on the immune system dysfunction in the diabetes mellitus. Annals of the Romanian Society for Cell Biology 15(1): 241–246.
Guinan E C. (2011). Diagnosis and management of aplastic anemia. Hematology ASH Education Program 2011: 76–81. https://doi.org/10.1182/asheducation-2011.1.76
Gupta V, Kumar A, Saini I and Saxena A K. (2013). Cytogenetic profile of aplastic anemia in Indian children. Indian Journal of Medical Research 137(3): 502–506. https://doi.org/10.1007/s12098-013-1242-1
Ho G T T, Wangensteen H and Barsett H. (2017). Elderberry and elderflower extracts, phenolic compounds, and metabolites and their effect on complement, RAW 264.7 macrophages and dendritic cells. International Journal of Molecular Sciences 18(3): 1–17. https://doi.org/10.3390/ijms18030584
Kaplowitz N. (2004). Drug-induced liver injury. Clinical Infectious Diseases 38: 44–48. https://doi.org/10.1086/381446
Kinoshita E, Hayashi K, Katayama H, Hayashi T and Obata A. (2012). Anti-influenza virus effects of elderberry juice and its fractions. Bioscience, Biotechnology, and Biochemistry 76(9): 1633–1638. https://doi.org/10.1271/bbb.120112
Maluf E, Hamerschlak N, Cavalcanti A B, Júnior AA, Eluf-Neto J, Falcão R P, Lorand-Metze I G, et al. (2009). Incidence and risk factors of aplastic anemia in Latin American countries: The LATIN case-control study. Haematologica 94(9): 1220–1226. https://doi.org/10.3324/haematol.2008.002642
Muthukumaraswamy P K. (2004). Post graduate medicine: bone marrow failure syndromes: an overview. Mumbay, India: Indian College of Physicians.
Nagarathna P K M, Reena K, Reddy S and Wesley J. (2013). Review on immunomodulation and immunomodulatory activities of some herbal plants. International Journal of Pharmaceutical Sciences Review and Research 22(1): 223–230.
Olaleye M T, Amobonye A E, Komolafe K and Akinmoladun A C. (2014). Protective effects of Parinari curatellifolia flavonoids against acetaminophen-induced hepatic necrosis in rats. Saudi Journal of Biological Sciences 21(5): 486–492. https://doi.org/10.1016/j.sjbs.2014.06.005
Putra W E and Rifa’i M. (2019). Hematopoiesis activity of Sambucus javanica on chloramphenicol-induced aplastic anemia mouse model. Natural Product Sciences 25(1): 59–63. https://synapse.koreamed.org/DOIx.php?id=10.20307/nps.2019.25.1.59 https://doi.org/10.20307/nps.2019.25.1.59
Putra W E, Soewondo A and Rifa’i M. (2015). Effect of dexamethasone administration toward hematopoietic stem cells and blood progenitor cells expression on BALB/c mice. The Journal of Pure and Applied Chemistry Research 4(3): 100–108. https://doi.org/10.21776/ub.jpacr.2015.004.03.221
Putra W E, Wafaretta E, Ardiana O, Januarisasi I D, Soewondo A and Rifa’i M. (2017). Dexamethasone-administrated BALB/c mouse promotes proinflammatory cytokine expression and reduces CD4+CD25+ regulatory T cells population. Bioscience Research 14(2): 201–213.
Rao K V. (2014). Pharmacotherapy: a pathophysiologic approach, 9E; drug-induced hematologic disorders. New York, USA: McGraw-Hill.
Segel G B and Lichtman M A. (2010). Williams hematology, 8E; aplastic anemia: Acquired and inherited. New York, USA: McGraw-Hill.
Shukla P, Bansode F W and Singh R K. (2011). Chloramphenicol toxicity: A review. Journal of Medicine and Medical Sciences 2(13): 1313–1316.
Ulbricht C, Basch E, Cheung L, Goldberg H, Hammerness P, Isaac R, Khalsa K P, Room A, Rychlik I, Varghese M, Weissner W, Windsor R C and Wortley J. (2014). An evidence-based systematic review of elderberry and elderflower (Sambucus nigra) by the Natural Standard Research Collaboration. Journal of Dietary Supplements 11(1): 80–120. https://doi.org/10.3109/19390211.2013.859852
Yeap S K, Rahman M B A, Alitheen N B, Ho W Y, Omar A R, Beh B K and Ky H. (2011). Evaluation of immunomodulatory effect: Selection of the correct targets for immunostimulation study. American Journal of Immunology 7(2): 17–23. https://doi.org/10.3844/ajisp.2011.17.23
Young N S and Kaufman D W. (2008). The epidemiology of acquired aplastic anemia. Haematologica 93(4): 489–492. https://doi.org/10.3324/haematol.12855
Yuan Z R and Shi Y. (2008). Chloramphenicol induces abnormal differentiation and inhibits apoptosis in activated T cells. Cancer Research 68(12): 4875–4881. https://doi.org/10.1158/0008-5472.CAN-07-6061