Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatmentReport as inadecuate




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BMC Complementary and Alternative Medicine

, 13:258

Basic research

Abstract

BackgroundNew alternatives for the treatment of Tuberculosis TB are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid UA and oleanolic acid OA.

MethodsThe activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB-c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR.

ResultsThe in vitro assay showed that the UA-OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB-c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals.

ConclusionUA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB.

KeywordsTriterpenoids Antitubercular activity Antimycobacterial activity Medicinal plants AbbreviationsABSAntibiotic

AIDSAcquired immunodeficiency syndrome

ANOVAOne-way analysis of variance

ATCCAmerican type culture collection

BSABovine serum albumin

CFUColony-forming units

CMICellular mediated immunity

CNICComision nacional de investigación científica

COX-2Ciclooxygensase type 2

C. tepejiloteChamaedora tepejilote

DMEMDulbecco’s modified Eagle’s medium

DMSODimethyl sulfoxide

DOTSDirectly observed therapy short course

DRDrug-resistant

EMBEtambutol

FBSFetal bovine serum

HBSSHank’s balanced salt solutions

HandEHematoxylin and eosin

HIVHuman immunodeficiency virus

IFN-γInterferon gamma

ILinterleukin

iNOSinducible Nitric oxide synthasa

IMSSMInstituto Mexicano del Seguro Social Mexico

INHIsoniazid

ISSIsotonic saline solition

i.tIntratracheallyIsoniazid

L. hispidaLantana hispida

MABAMicroplate alamar blue assay

MDRMultidrug-resistant

MICMinimum inhibitory concentration

M. aviumMycobacterium avium

M. chelonaeMycobacterium chelonae

M. fortuitumMycobacterium fortuitum

M. smegmatisMycobacterium smegmatis

M. tuberculosisMycobacterium tuberculosis

MScMaster science

NF-κBNuclear factor-kappaB

NONitric oxide

OAOleanolic acid

OADCOleic acid-albumin, dextrose and catalase

PBSPhosphate buffered saline

PGE2Prostaglandin E-2

RPM1Roswell Park Memorial Institute1

RFURelative fluorescent unit

RIFRifampicin

s.c.Subcutaneous

SDSSodium dodecyl sulfate

SDStandard deviation

STRStreptomycin

TBTuberculosis

TGF-β1Transforming growth factor-beta 1

TNF-αTumor necrosis factor alpha

UAUrsolic acid

XDRExtensively drug-resistant

WHOWorld health organization.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6882-13-258 contains supplementary material, which is available to authorized users.

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Author: Adelina Jiménez-Arellanes - Julieta Luna-Herrera - Jorge Cornejo-Garrido - Sonia López-García - María Eugenia Castro-Mus

Source: https://link.springer.com/



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