Abstract
For many years, tuberculosis (TB) has been a major public health problem worldwide. Advances for treatment and eradication have been very limited. Silymarin (Sm) is a natural product with antioxidant and hepatoprotective activities that has been proposed as a complementary medicine to reduce the liver injury produced by the conventional anti-TB chemotherapy. Sm also has immunoregulatory and microbicide properties. In this study, we determined the effect of Sm on the growth control of mycobacteria. In vitro studies showed that Sm and Silibinin (the principal active compound of Sm) have microbicidal activity against drug-sensitive and multidrug-resistant (MDR) mycobacteria, induce the production of protective cytokines from infected macrophages, and improve the growth control of mycobacteria (p ≤ 0.0001). Studies in vivo using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive or MDR mycobacteria have shown that Sm induces significant expression of Th-1 cytokines such as IFN-γ and IL-12 as well as TNFα, which produce significant therapeutic activity when administered alone and apparently have a synergistic effect with chemotherapy. These results suggest that Sm has a bactericidal effect and can contribute to the control and establishment of a TH1 protective immune response against mycobacterial infection. Thus, it seems that this flavonoid has a promising potential as adjuvant therapy in the treatment of TB.
Highlights
Tuberculosis (TB) is an ancient infection caused by Mycobacterium tuberculosis
We investigated the direct effect of Sm on mycobacteria viability, its effect in human monocyte-derived macrophages infected with mycobacteria and the therapeutic effect in infected mice with drug-sensitive and MDR strains, treated with Sm alone or in combination with chemotherapy
To determine the bacillary loads in Mø treated with Sm or Sb, Human monocyte-derived macrophages (hMDMs) cells were cocultured for 4 h with M. tuberculosis H37Rv or clinical isolate CIBIN 99 (MDR) strains at a multiplicity of infection (MOI) of 5:1
Summary
Tuberculosis (TB) is an ancient infection caused by Mycobacterium tuberculosis. According to a WHO report, in the past year, 10.4 million people have developed active TB worldwide, and 1.4 million die each year [1, 2, 3]. To reduce the hepatic damage produced by the treatment, some authors have proposed the use of natural complementary therapies and even the use of herbal extracts with hepatoprotective activity [16, 17, 18, 19]. In countries such as China, hepatoprotective drugs are prescribed alongside anti-TB treatment [20, 21, 22]. Sm has been used as a natural medicine for more than 2000 years [44], the effects of its immunomodulatory and anti-inflammatory activities during mycobacterial infections remain unknown. We investigated the direct effect of Sm on mycobacteria viability, its effect in human monocyte-derived macrophages infected with mycobacteria and the therapeutic effect in infected mice with drug-sensitive and MDR strains, treated with Sm alone or in combination with chemotherapy
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