American Journal of Microbiological Research
ISSN (Print): 2328-4129 ISSN (Online): 2328-4137 Website: Editor-in-chief: Apply for this position
Open Access
Journal Browser
American Journal of Microbiological Research. 2015, 3(1), 8-13
DOI: 10.12691/ajmr-3-1-2
Open AccessArticle

The Effect of the Petroleum Ether Extracts from Mangosteen Pericarp (Garcinia mangostana L.) on Interferon-gammaand, Interleukin-12 Activities in AlbinoWistar Rats (Rattus norvegicus) Infected with Mycobacterium tuberculosis

Martha Kaihena1, Syamsu2, Yadi Yasir3 and Mochammad Hatta4,

1Biology Study Programm, Faculty of Mathematic and Sciences, Pattimura University, Ambon, Indonesia

2Department of Internal Medicine, Faculty of Medicine, Hasanudin University, Makassar, Indonesia

3Department of Microbiology, Faculty of Medicine, Mulawarman University, Samarinda, Indonesia

4Molecular Biology and Immunology Laboratory for Infectious Diseases, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Pub. Date: January 07, 2015

Cite this paper:
Martha Kaihena, Syamsu, Yadi Yasir and Mochammad Hatta. The Effect of the Petroleum Ether Extracts from Mangosteen Pericarp (Garcinia mangostana L.) on Interferon-gammaand, Interleukin-12 Activities in AlbinoWistar Rats (Rattus norvegicus) Infected with Mycobacterium tuberculosis. American Journal of Microbiological Research. 2015; 3(1):8-13. doi: 10.12691/ajmr-3-1-2


Background. Garcinia mangostana L(GML) pericarp extract is known to contain active substances called Xanthones (α, β and γ Mangosteens) which is the biggest derivative and has strong antioxidant effects. This substance also has antiinflammatory, antilipid, anticancer, antibacteria and antituberculosis effects. However, its mechanism is still unclear. Mycobacterium tuberculosis (M. tuberculosis) invasion into the lungs through the respiratory tract can cause severe infection. The body has an immune system which controls infection by eliminating germs to ease the burden of infection. Interferon gamma (IFN- γ) and Interleukin 12 (IL-12) acts as positive feedback in stimulating macrophages to kill M. tuberculosis. During this process, oxidative compounds (ROI,RNI,NO) that plays an important role in the phagolysosome fusion process are produced. Not only does the consumption of GML pericarp extract as an antioxidant becomes the immunomodulator to enhance the immune’s activities, it also functions as an antioxidant that can neutralize the oxidative compounds produced by the immune system. The aim of this study was to determine the effect of EPEBh GML on IFN-γ and IL-12 secretion activities in mice infected with M. tuberculosis. Materials and method. This study used 30 Wistar rats, 150-200g of weight and 8-10 weeks old. Rats were randomly divided into 6 groups each consisting of 5 rats, including the negative control (without infection and without EPEKBh GML intervention) and a positive control (rats were infected with M.tb H37Rv at a dose of 106cfuas much as 0.2 ml through the trachea for 6 weeks). Once infected, the rats were then intervened with EPEKBhGML 30, 60, 120 dose and 180 mg/kg bodyweigh/day for 1 month. Afterward the rats were necropsied and dissected for the blood to be taken directly from the heart. Levels of IFN-γ and IL-12 were analyzed using the ELISA method. Data were then analyzed using One-Way ANOVAtest followed by Post-Hoc test (LSD), a significant P <0.05, to assess the comparison between groups. Results. Results show that EPEKBh GML significantly affect the rise of IFN-γ levels, with a P value 0,000<0,05 and IL-12, with a P value of 0,045 <0,05. Conclusion. EPEKBh GML was effective in increasing the activity of IFN-γ and IL-12 and the most effective dose to increase IFN-γ and IL-12activity was 120 mg/kgbody weight/day. Also, increasing the dose to a higher dosage had no effect on IFN-γ and IL-12 activity, in fact it tended to decline.This results need to further study to understand what the reason.

extract Garcinia mangostanal. IFN- γ IL-12 Mycobacterium tuberculosis

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


[1]  WHO: Global Tuberculosis Report 2013. WHO Press 2013:
[2]  Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis. N Engl J Med. 2013, 368:745-55.
[3]  Smith I. Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence. Clinical Microbiology Reviews 2003, 16(3): 463-496.
[4]  Subagyo A., T.Y Aditama., Sutoyo D.K. dan L.G Partakusuma. Pemeriksaan Interferon-gamma Dalam Darahuntuk DeteksiInfeksi Tuberkulosis, JTI 3(2). 6-15.
[5]  Schluger NW,Ro WN. The Host Immune To Tuberculosis. AmJRespir; Crite Care Med 1998, Vol157. pp 79-691.
[6]  Gouzy A, Larrouy-Maumus G, Bottai D, Levillain F, Dumas A, et al. Mycobacterium tuberculosis Exploits Asparagine to Assimilate Nitrogen and Resist Acid Stress during Infection. PLoSPathog. 2014, 10(2): e1003928.
[7]  Lange C, Abubakar I, Alffenaar J-WC, et al. Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement. The European Respiratory Journal 2014; 44(1): 23-63.
[8]  Gaude GS, Hattiholli J, Kumar P. Risk factors and drug-resistance patterns among pulmonary tuberculosis patients in northern Karnataka region, India. Nigerian Medical Journal: Journal of the Nigeria Medical Association 2014, 55(4):327-332.
[9]  Mendez AP., RaviglioneMC.,Laszlo A., Binkin N., Rieder HL., Bustreo F., Cohn DL., Weezenbeek CSBI., Kim SJ., Chaulet P., Nun P., Global surveillance for antituberculosis-drug resistance. 1994-1997. NEJM 1998, 338: 1641-9.
[10]  Indonesia Health Department,Guideline for Tuberculosis management. 8th Edition, Jakarta. Indonesia 2002.
[11]  Muchtar,A. Farmakologi Obat Antituberkulosis (OAT) Sekunder.JTI 2006, 3(2): 24-25.
[12]  WHO: Drug-Resistant Tb Surveillance & Response Supplement Global Tuberculosis Report 2014. WHO Press 2014:
[13]  vanCrevel R, Ottenhoff THM, van der Meer JWM. Innate immunity to Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2002, 15: 294-309.
[14]  Arora A, Nadkarni B, Dev G, Chattopadhya D, Jain AK, Tuli SM, Kumar S.The use of immunomodulators as an adjunct to antituberculous chemotherapy in non-responsive patients with osteo-articular tuberculosis. J Bone Joint Surg Br. 2006 Feb, 88(2): 264-9.
[15]  Jing J. Wang a,b, Qing H. Shi a,c, Wei Zhang a,b, Barbara J.S. Sanderson. Anti-skin cancer properties of phenolic-rich extract from the pericarpofmangosteen (Garciniamangostana Linn.). Food and Chemical Toxicology. 2012, 50:3004-3013.
[16]  Wang JJ, Zhang W, Sanderson BJS. Altered mRNA Expression Related to the Apoptotic Effect of Three Xanthones on Human Melanoma SK-MEL-28 Cell Line. BioMed Research International 2013, 2013:715603.
[17]  Jing J. Wang, Barbara J.S. Sanderson, Wei Zhang. Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen (Garciniamangostana Linn.) on human melanoma cells.Food and Chemical Toxicology, Volume 49, Issue 9, September 2011, Pages 2385-2391
[18]  Marcin Barański, Dominika Średnicka-Tober, Nikolaos Volakakis,, et al. Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. Br J Nutr. 2014; 112(5): 794-811.
[19]  Chomnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan W. Effect of Garciniamangostanaon inflammation caused by Propionibacteriumacnes. Fitoterapia 2007, 78: 401-8.
[20]  Supiyanty W, Wulansari ED, Kusmita L. Ujiaktivitasantioksidandanpenebtuankandunganantosianin total kulitbuahmanggis (Garciniamangostana L.) Sekolah Tinggi Ilmu Farmasi Yayasan Pharmasi Semarang. Majalah Obat Tradisional. 2010, 15 (2): 64-70.
[21]  Suksamrarn S., Panseeta P., Kunchanawatta S., Distaporn I., Ruktasing S., Suksamrarn A. Ceanothane–and Lupane-Type Triterpenes with Antiplasmodial and Antimycobacterial Activities with Antiplasmodial and from Ziziphuscambodiana. Chem. Pharm. Bull. 2006, 54(4)535 – 537.
[22]  Dahlan MS.Statistic for health and medicine (in Indonesia).SPSS : 5th edition. Jakarta:Salemba Medika, Indonesia 2012.
[23]  The AVMA Guidelines for the Euthanasia of Animals: 2013 Edition:
[24]  Peper A. Aspects of the Relationship Between Drug Dose and Drug Effect. Dose-Response 2009, 7(2): 172-192.
[25]  A. Gurib-Fakim. Review: Medicinal plants: Traditions of yesterday and drugs of tomorrow. Molecular Aspects of Medicine 2006, 1-93.
[26]  Susanto M., Zulfian, B. Kurniawan, A. Tjiptaningrum, Effects of Garciniamangostana L. against AST and ALT activity in Rattusnovergicus induced by Isoniazid (in Indonesia). Medical Faculty Lampung University journal. 2013. 23: 378-381.
[27]  Pasaribu F, P.Sitorus S.Bahri, Effects of Garcinia Mangostana L.extraction in decreasing level glucosa in blood (in Indonesia). Journal of Fakultas Farmasi USU. 2012. 12: 142-149.
[28]  Darwich L, Coma G, Peña R, et al. Secretion of interferon-γ by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18. Immunology 2009, 126(3): 386-393.
[29]  Michel Denis. Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. Cellular Immunology, Volume 132, Issue 1, January 1991, Pages 150-157.
[30]  Christian Bogdan, Martin Röllinghoff, Andreas Diefenbach. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Current Opinion in Immunology, Volume 12, Issue 1, 1 February 2000, Pages 64-76.
[31]  Kubota K. Innate IFN-γ production by subsets of natural killer cells, natural killer T cells and γδ T cells in response to dying bacterial-infected macrophages. Scand J Immunol 2010, 71: 199-20910.
[32]  Janis E. Wigginton and Denise Kirschner. A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection with Mycobacterium tuberculosis. J Immunol. 2001, 166: 1951-1967.
[33]  Emily Gwyer Findlay and Tracy Hussell, “Macrophage-Mediated Inflammation and Disease: A Focus on the Lung,” Mediators of Inflammation 2012, Article ID 140937, 6 pages, 2012.
[34]  Tostman A, Boeree MJ, Aarnouts RE, de Lange WC, Van der Ven AJAM, and Dekhuijen R.. Antituberculosis drug-induced hepatotoxicity: Concise up-to-date review. Journal of Gastroenterology and Hepatology 2007.
[35]  Akiibinu MO., Ogunyemi EO, Arinola OG, AdenaikeAf, and Adegoke OD. Level of Oxidatif Metabolites Antioxidants and Neopterin in Nigerian Pulmonary Tuberculosis PatientsEur.J.Gen.Med. 2011, 5(4): 208-211.
[36]  Venketaraman V, Dayaram YK, Talaue MT, dan Connell ND. 2005. Glutathione and Nitrosoglutathione in macrophage defense against M. tuberculosis. Infect Immunity.
[37]  Guerra C, Johal K, Morris D, et al. Control of Mycobacterium tuberculosis growth by activated natural killer cells. Clinical and Experimental Immunology 2012, 168(1): 142-152.