Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment

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.

Standardized Extract of Mangifera Indica L. Leaves as an Antimycobacterial and Immunomodulatory Agent

“…This supports the ability of HEMIL to stimulate the B-cells in response to the SRBCs antigen and improve the primary humoral immune response. 34 Similar results have been reported for the polysaccharide from Angelica sinensis 29 and aqueous extract of Gynostemma pentaphyllum. 37 Augmentation of the humoral response to SRBCs was also evident from the significantly increased (P<0.001) number of PFCs in the spleen of mice (Table 4) which can be correlated to the number of B-cells producing SRBC-specific IgM or antigen presenting cells.…”

“…Terpenoids and other phytochemical constituents including squalene, β-sitosterol, oleanolic acid, ursolic acid, farnesol, methylic ester of hexadecanoic acid, etc have been reported for their inhibitory activity against MTB. 34 Therefore, the effect shown by HEMIL may be attributed to the terpenoids present in it. These findings need to be confirmed in MDR strains of MTB along with the evaluation of MTB inhibition within macrophages.…”

Update: Biological and Chemical Aspects of Senna spectabilis

“…Often, this metabolite is studied in association with ursolic acid, demonstrating relevant pharmacological properties. 75 More recently, Jimenez-Arellanes et al 76 revealed that both isomers act in synergism against Mycobacterium tuberculosis, promoting a rapid elimination of the pathogen.…”

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

“…Another study showed that UA and OA found to have synergistic activity. Intracellular activity of these two compounds can inhibit the growth of mycobacteria at low doses [16].…”

“…In addition, UA and OA also have similar chemical structure that makes them have similar characteristic in pharmacology properties [16,17].…”