Macrophage Activation by Ursolic and Oleanolic Acids during Mycobacterial Infection.

Oleanolic (OA) and ursolic acids (UA) are triterpenes that are abundant in vegetables, fruits and medicinal plants. They have been described as active moieties in medicinal plants used for the treatment of tuberculosis. In this study, we analyzed the effects of these triterpenes on macrophages infected in vitro with Mycobacterium tuberculosis (MTB). We evaluated production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines (TNF-α and TGF-ß) as well as expression of cell membrane receptors (TGR5 and CD36) in MTB-infected macrophages following treatment with OA and UA. Triterpenes caused reduced MTB growth in macrophages, stimulated production of NO and ROS in the early phase, stimulated TNF-α, suppressed TGF-ß and caused over-expression of CD36 and TGR5 receptors. Thus, our data suggest immunomodulatory properties of OA and UA on MTB infected macrophages. In conclusion, antimycobacterial effects induced by these triterpenes may be attributable to the conversion of macrophages from stage M2 (alternatively activated) to M1 (classically activated).

[The role of alexithymia as a psychosomatic factor in psoriasis]. / El papel de la alexitimia como factor psicosomático en la psoriasis.

BACKGROUND: Alexithymia is the lack of mental representations of emotions leading to limited ability to understand and regulate these and can contribute to the development or maintenance of a psychosomatic illness. The aim of the study was to demonstrate that alexithymia is a feature that occurs more frequently in patients with psoriasis and that the coexistence of alexitimia-psoriasis is associated with high levels of trait anxiety. METHODS: We applied the Toronto Alexithymia Scale -20 (TAS-20), Inventory of state-trait anxiety (STAI) to 16 outpatients with psoriasis of Dermatology Service of Hospital de Especialidades (Centro Médico Nacional Siglo XXI) and the results were compared with 25 control subjects. RESULTS: 25 % of patients with psoriasis presented alexitimia, while in the control group was 8 % (p = 0.002). Correlation between the scores of the TSA-20 and STAI-trait (r = 0.6957, p < 0.0001) was observed. CONCLUSIONS: The alexitimia occurs more frequently in individuals with psoriasis than in the general population, and levels of trait anxiety in individuals with psoriasis are similar regardless of the presence of alexithymia.

Introducción: la alexitimia consiste en la carencia de representaciones mentales de las emociones que conduce a una capacidad limitada para comprender y regular estas, y que puede contribuir en el desarrollo o mantenimiento de una enfermedad psicosomática. El objetivo de este estudio fue demostrar que la alexitimia es una característica que se presenta más frecuentemente en pacientes con psoriasis y que la coexistencia de alexitimia-psoriasis se asocia, como rasgo, a niveles altos de ansiedad. Métodos: la escala de alexitimia de Toronto-20 (TAS- 20) y el inventario de ansiedad estado-rasgo (IDARE) se aplicaron a 16 pacientes con psoriasis de la consulta externa de Dermatología del Hospital de Especialidades del Centro Médico Nacional Siglo XXI y se compararon con 25 individuos control. Resultados: de los pacientes con psoriasis, 25 % presentaron alexitimia, mientras que en el grupo control fue un 8 % (p = 0.002). Se observó correlación entre las puntuaciones de la TSA-20 y del IDARE-rasgo (r = 0.6957, p < 0.0001). Conclusiones: la alexitimia se presenta con mayor frecuencia en individuos con psoriasis que en la población en general y los niveles de ansiedad como rasgo en individuos con psoriasis son similares, independientemente de la presencia de alexitimia.

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

BACKGROUND: New 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). METHODS: The 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. RESULTS: The 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. CONCLUSION: UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB.