Thymoquinone (TQ) inhibits the replication of intracellular Mycobacterium tuberculosis in macrophages and modulates nitric oxide production

Abstract

BackgroundHuman tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent.MethodsIn this study, the effects of TQ on intracellular mycobacterial replication are examined in macrophages. In addition, its effect on mycobacteria-induced NO production and pro-inflammatory responses were investigated in Mycobacterium tuberculosis (MTB)-infected Type II human alveolar and human myeloid cell lines.ResultsTQ at concentrations ranging from 12.5 to 25 μg/mL and 6.25 to 12.5 μg/mL reduced intracellular M. tuberculosis H37Rv and extensively drug-resistant tuberculosis (XDR-TB) 72 h post-infection in RAW 264.7 cells. TQ treatment also produced a concentration-dependent reduction in nitric oxide production in both H37Rv and XDR-TB infected RAW 264.7 cells. Furthermore, TQ reduced the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory molecules such as tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6) in H37Rv-infected cells and eventually reduced pathogen-derived stress in host cells.ConclusionsTQ inhibits intracellular H37Rv and XDR-TB replication and MTB-induced production of NO and pro-inflammatory molecules. Therefore, along with its anti-inflammatory effects, TQ represents a prospective treatment option to combat Mycobacterium tuberculosis infection.

Nigella sativa essential oil and its bioactive compounds as resistance modifiers against Staphylococcus aureus

“…In case of Mycobacterium tuberculosis , the increasing drug resistance is a current threat to public health. Thq inhibited the replication of the extensively drug‐resistant M. tuberculosis inside of macrophages, and Thq inhibited the production of nitric oxide induced by M. tuberculosis (Mahmud et al, ).…”

Dysregulated circRNAs in plasma from active tuberculosis patients

“…Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major public health concern . Despite advances in the effective treatment of TB in recent years, the number of annual deaths remains almost unchanged and it is estimated that TB results in the death of about 1.5 million individuals annually, making it the most prevalent bacterial infection.…”

Comparative Immunomodulatory Activity of Nigella sativa L. Preparations on Proinflammatory Mediators: A Focus on Asthma

“…In human monocytes, the anti-inflammatory effects observed by the treatment with NS are not reported in the literature so far. Some studies showed that TQ alone suppressed the expression of IL-6 from Mycobacterium tuberculosis infected human monocyte THP-1 cells ( Mahmud et al, 2017 ). Furthermore, TQ inhibited the production of IL-6 in LPS-activated murine macrophage-like RAW264.7 cells ( Hossen et al, 2017 ).…”