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Dietary Flavonoids for Tuberculosis?

A recent study from the Western University of Health Sciences found strong evidence for the anti-mycobacterial potential of flavonoids on tuberculosis infection in at-risk populations.

Tuberculosis (TB) is the leading cause of death by infectious diseases with an estimated one-quarter of the world’s population testing positive for Mycobacterium tuberculosis (Mtb). Effective TB treatment is difficult, and approximately 20% of TB cases are now resistant to at least one of the first- or second-line anti-TB drugs. Given the public health burden of TB, considerable effort is being expended to find alternative treatment options to combat this devastating disease and unconventional treatment approaches are being examined. Flavonoids, plant-derived natural products with a broad spectrum of biological activity, have been shown to exert a variety of health benefits including protective effects against chronic diseases. The authors hypothesized flavonoid intake would have a favorable influence on the resolution of Mtb, but the effects of flavonoids on Mtb infectivity has received little attention. The recent study reported by Cao and Venketaraman (Molecules, 2019, 24, 851) investigated the effects of polyphenol flavonoids on markers of Mtb disease in human and cell culture models of Mtb infection. The authors investigated the activity of a mixed flavonoid supplement (MFS) containing monomeric flavonoids, wild bilberry fruit, and green tea leaf extracts in an experimental model system of TB. Here, the authors investigated the effects of MFS on Mtb cell growth in vitroin viability assays and in vivo by the induction of granuloma formation in infected patients. They also measured changes in levels of the oxidative stress marker glutathione (GSH) and regulation of inflammatory cytokines. The resulting experimental granuloma formation was assessed with routine hematoxylin and eosin staining, cytokines were detected with commercial ELISA kits, and GSH was measured using the Glutathione (GSH) Colorimetric Detection Kit (K006-H1) from Arbor Assays.

MFS treatment significantly reduced intracellular Mtbsurvival in both cultured macrophages and isolated peripheral blood mononuclear cells from infected human samples. Human subjects treated with MFS showed increased granuloma formation, an increase in pro-inflammatory cytokines IL-12 and IFN-γ, and increased GSH levels. The strong anti-mycobacterial effects demonstrated by augmented granuloma formation were closely linked to increased bacterial containment and improved host protection. Upregulation of pro-inflammatory cytokines indicated enhanced activation of immunological defense mechanisms. Interestingly, elevated levels of intracellular GSH were associated with mycobactericidal effects in both a direct and indirect immunomodulating manner through downstream mediators.

Collectively, the results demonstrate that MFS treatment strongly inhibits Mtb infectivity and suggest increased flavonoid intake as an attractive adjunctive strategy for managing TB.

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