IN VITRO STUDY OF URSOLIC ACID COMBINATION FIRST-LINE ANTITUBERCULOSIS DRUGS AGAINST DRUG-SENSITIVE AND DRUG-RESISTANT STRAINS OF Mycobacterium tuberculosis


Dian Ayu Eka Pitaloka, Elin Yulinah Sukandar

Abstract


Objective: The resurgence of tuberculosis (TB) caused by Mycobacterium TB (MTB) is associated with the rapid spread of multidrug-resistant,
therefore, the development of new antimycobacterial agents is necessary. The aim of this study was to evaluate the antimycobacterial activity of
ursolic acid (UA) when it using alone and combination with TB drugs.

Methods: MTB H37Rv strain, streptomycin-rifampicin resistant strain, and isoniazid-ethambutol resistant strain were evaluated by susceptibility test
using a serial number of UA (25-150 µg/mL). Minimum inhibitory concentration (MIC) was read as minimum concentration of drugs that completely
inhibit visible growth of organism. Activities of drug combination of UA with TB drug were determined in Lowenstein-Jensen media by calculating
the fractional inhibitory concentration index.

Results: The results showed that MIC of UA was 50 µg/mL against three different strains of MTB. The combination of UA and TB drugs displayed
synergistic interaction, and no antagonism result from the combination was observed for strains of MTB.

Conclusion: These results indicate that UA may serve as a promising lead compound for future antimycobacterial drug development.

Keywords: Ursolic acid, Tuberculosis, Drug combination, Susceptibility test


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References


Ducati RG, Ruffino-Netto A, Basso LA, Santos DS. The resumption of consumption -- a review on tuberculosis. Mem Inst Oswaldo Cruz 2006;101(7):697-714.

World Health Organization. Tuberculosis. 2014, August. Available from: http://www.who.int/tb/en/. [Last cited on 2016 Aug].

Codruta S, Camelia O, Florin B, Corina D, Cristina T, Dorina C, et al. The synergistic biologic activity of oleanolic and ursolic acids in complex with hydroxypropyl-γ-cyclodextrin. Molecules 2014;19:4924-40.

Gayatri R, Kalpana DP, Gunassekaran GR, Dhanapal S. Protective role of ursolic acid in den induced oxidative stress mediated hepatocellular carcinoma - A focus on thiol status. Int J Pharm Pharm Sci 2010;2(4):140-6.

López-García S, Castañeda-Sanchez JI, Jiménez-Arellanes A, Domínguez-López L, Castro-Mussot ME, et al. Macrophage activation by ursolic and oleanolic acids during Mycobacterial infection. Molecules 2015;20(5):14348-64.

Daiane M, Lillian LC, Daniela FR, Kahlil SS, Pedro EA, Barison A, et al. Anti-tuberculosis activity of oleanolic and ursolic acid isolated from the dichloromethane extract of leaves from Duroia macrophylla. BMC 2013;8:1-2.

De Logu A, Onnis V, Saddi B, Congiu C, Schivo ML, Cocco MT. Activity of a new class of isonicotinoylhydrazones used alone and in combination with isoniazid, rifampicin, ethambutol, para-aminosalicylic acid and clofazimine against Mycobacterium tuberculosis. J Antimicrob Chem 2000;49(2):275-82.

World Health Organization. Fixed-Dose Combination Tablets for the Treatment of Tuberculosis. Report of an Informal Meeting in Geneva; 1999.

Drake JW. The distribution of rates of spontaneous mutation overviruses, prokaryotes, and eukaryotes. Ann N Y Acad Sci 1999;870;100-7.

East African, British Medical Research Councils. Controlled trial offive short course regimens of chemotherapy regimens for pulmonary tuberculosis. Am Rev Respir Dis 1981;123:165-70.

Takayama K, Kilburn JO. Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis. Antimicrob Agents Chemother 1989;33(9):1493-9.

Telenti A, Imboden P, Marchesi F, Lowrie D, Cole S, Colston MJ, et al. Detection of rifampicin-resistance mutations in Mycobacterium tuberculosis. Lancet 1993;341(8846):647-50.

Liu J. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 1995;49(2):57-68.

Zhang Y, Yew WW. Mechanisms of drug resistance in Mycobacterium tuberculosis. Int J Tuberc Lung Dis 2009;13(11):1320-30.

Wójciak-Kosior M. Separation and determination of closely related triterpenic acids by high performance thin-layer chromatography after iodine derivatization. J Pharm Biomed Anal 2007;45(2):337-40.

Jiménez-Arellanes A, Luna-Herrera J, Cornejo-Garrido J, López-García S, Castro-Mussot ME, Meckes-Fischer M, et al. Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment. BMC Complement Altern Med 2013;13:258.

Mestry D, Dighe V. Separation and determination of triterpene acids by using high performance thin layer chromatography from stem bark of Mimusops elengi Linn. Int J Pharm Pharm Sci 2014;6(1):313-7.

Ge F, Zeng F, Liu S, Guo N, Ye H, Song Y, et al. In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis. J Med Microbiol 2010;59:567-72.

Joseph B, Priya MR. In vitro antimicrobial activity of Psidium Guajava l. Leaf essential oil and extracts using agar well diffusion method. Int J Curr Pharm Rev Res 2010;2(3):28-32.

Kurek A, Grudniak AM, Szwed Ma, Klicksa A, Samluk L, Wolska K, et al. Oleanolic acid and ursolic acid affect peptidoglycan metabolism in Listeria monocytogenes. Antonie Van Leuwenhoek 2010;97:61-8.

Deng JZ, Starck SR, Hecht SM. Pentacyclic triterpenoids from Freziera sp. that inhibit DNA polymerase beta. Bioorg Med Chem 2000;8(1):247-50.




About this article

Title

IN VITRO STUDY OF URSOLIC ACID COMBINATION FIRST-LINE ANTITUBERCULOSIS DRUGS AGAINST DRUG-SENSITIVE AND DRUG-RESISTANT STRAINS OF Mycobacterium tuberculosis

DOI

10.22159/ajpcr.2017.v10i4.16582

Date

01-04-2017

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Vol 10 Issue 4 April 2017 Page: 216-218

Print ISSN

0974-2441

Online ISSN

2455-3891

Statistics

51 Views | 64 Downloads

Authors & Affiliations

Dian Ayu Eka Pitaloka
Institut Teknologi Bandung
Indonesia

Elin Yulinah Sukandar


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