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. 2019 Feb 28;24(5):851.
doi: 10.3390/molecules24050851.

Flavonoid Mixture Inhibits Mycobacterium tuberculosis Survival and Infectivity

Ruoqiong Cao  1 , Garrett Teskey  2 , Hicret Islamoglu  3 , Myra Gutierrez  4 , Oscar Salaiz  5 , Shalok Munjal  6 , Marcel P Fraix  7 , Airani Sathananthan  8 , David C Nieman  9 , Vishwanath Venketaraman  10
Affiliations

Flavonoid Mixture Inhibits Mycobacterium tuberculosis Survival and Infectivity

Ruoqiong Cao et al. Molecules. .

Abstract

Background: Flavonoids have been shown to exert anti-pathogenic potential, but few studies have investigated their effects on Mycobacterium tuberculosis (Mtb) infectivity. We hypothesized that a flavonoid mixture would have a favorable influence on cell death and the resolution of Mtb infection in THP-1 macrophages and in granulomas derived from both healthy participants and those with type 2 diabetes mellitus (T2DM).

Methods: THP-1 macrophages, and in vitro granulomas from healthy participants (N = 8) and individuals with T2DM (N = 5) were infected with Mtb. A mixed flavonoid supplement (MFS) at a concentration of 0.69 mg per ml was added as treatment to Mtb infected THP-1 macrophages and granulomas for 8 to 15 days.

Results: MFS treatment significantly reduced the intracellular Mtb survival, increased cell density, aggregation, and granuloma formation, and increased glutathione (GSH) levels. IL-12 and IFN-γ levels tended to be higher and IL-10 lower when Mtb infected THP-1 macrophages and granulomas obtained from healthy subjects were treated with MFS compared to control.

Conclusions: MFS treatment exerted a strong influence against Mtb infectivity in THP-1 macrophages and in granulomas including antimycobacterial effects, GSH enrichment, cytokine regulation, and augmented granuloma formation. Our data support the strategy of increased flavonoid intake for managing tuberculosis.

Keywords: Mtb; Mycobacterium tuberculosis; T2DM; TB; flavonoids; glutathione; immunomodulation; polyphenols.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Growth of Mtb Erdman in 7H9 containing MFS. Experiments were performed in order to determine direct mycobacterial effects of each treatment. Data represent means ±SE from 1 trial and plating it multiple times. * p < 0.05 when comparing samples to their respective controls.
Figure 2
Figure 2
Hematoxylin and Eosin staining of untreated and MFS-treated samples of THP-1 cells. Microscopy work was done under 100×.
Figure 3
Figure 3
Survival of Mtb Erdman inside untreated and MFS-treated THP-1 macrophages. Data represent means ±SE from 6 trials and multiple plating times. ** p < 0.005 when comparing MFS-treated samples to untreated samples at 12 days.
Figure 4
Figure 4
Levels of IL-10 in untreated and MFS-treated THP-1 cells. Assay of IL-10 was performed using an enzyme-linked immunosorbent assay (ELISA) Ready-Set-Go kit from eBioscience. Data represent means ±SE from 6 trials.
Figure 5
Figure 5
Levels of total Glutathione (GSH) in untreated and MFS-treated THP-1 cells. Corrections were made to total protein measured by BCA Protein Assay Kit from Thermo Scientific. Data represent means ±SE from 6 trials. *** p < 0.0005 when comparing GSH levels from control and MFS treated groups.
Figure 6
Figure 6
Hematoxylin and Eosin staining of untreated and MFS-treated human granulomas from healthy subjects. Microscopy work was done with a light microscope at 100× magnification under oil immersion.
Figure 7
Figure 7
Survival of Mtb Erdman inside untreated and MFS-treated granulomas from healthy subjects. Data represent means ±SE from eight healthy individuals. ** p < 0.005 when comparing samples at 15 days.
Figure 8
Figure 8
Levels of total GSH in untreated and MFS-treated granulomas from healthy subjects. Data represent means ±SE from eight healthy individuals. ** p < 0.005 when comparing GSH levels in control and MFS-treated groups.
Figure 9
Figure 9
Assay of IL-12 in the supernatants from untreated and MFS-treated granulomas from healthy subjects. Assay of IL-12 was performed using an ELISA Ready-Set-Go kit from eBioscience. Data represent means ±SE from eight healthy individuals.
Figure 10
Figure 10
Assay of IFN-γ in the supernatants from untreated and MFS-treated granulomas from healthy subjects. Assay of IFN-γ was performed using an ELISA Ready-Set-Go kit from eBioscience. Data represent means ±SE from eight healthy individuals.
Figure 11
Figure 11
Assay of IL-10 in the supernatants from untreated and MFS-treated granulomas from healthy subjects. Assay of IL-10 was performed using an ELISA Ready-Set-Go kit from eBioscience. Data represent means ±SE from eight healthy individuals.
Figure 12
Figure 12
Hematoxylin and Eosin staining of untreated and MFS-treated human granulomas from individuals with T2DM. Microscopy work was done with a light microscope at 100× magnification under oil immersion.
Figure 13
Figure 13
Survival Mtb Erdman inside untreated and MFS-treated granulomas from individuals with T2DM. Data represent means ±SE from six T2DM individuals. * p < 0.05 when comparing untreated samples with samples treated with MFS at 15 days.
Figure 14
Figure 14
Survival of Mtb Erdman inside MFS-treated granulomas from healthy subjects and individuals with T2DM. Data represent means ±SE from six T2DM individuals and ±SE from healthy individuals.
Figure 15
Figure 15
Levels of IL-10 in untreated and MFS-treated granulomas from individuals with T2DM. Assay of IL-10 was performed using an ELISA Ready-Set-Go kit from eBioscience. Data represent means ±SE from six T2DM individuals.
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References

    1. World Health Organization . Global Tuberculosis Report 2015. World Health Organization; Geneva, Switzerland: 2015.
    1. Tacconelli E., Carrara E., Savoldi A., Harbarth S., Mendelson M., Monnet D.L., Pulcini C., Kahlmeter G., Kluytmans J., Carmeli Y., et al. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet. Infect. Dis. 2018;18:318–327. doi: 10.1016/S1473-3099(17)30753-3. - DOI - PubMed
    1. Lönnroth K., Roglic G., Harries A.D. Improving tuberculosis prevention and care through addressing the global diabetes epidemic: From evidence to policy and practice. Lancet Diabetes Endo. 2014;2:730–739. doi: 10.1016/S2213-8587(14)70109-3. - DOI - PubMed
    1. World Health Organization Diabetes. [(accessed on 30 July 2018)]; Available online: http://www.who.int/news-room/fact-sheets/detail/diabetes.
    1. Balentine D.A., Dwyer J.T., Erdman J.W., Jr., Ferruzzi M.G., Gaine P.C., Harnly J.M., Kwik-Uribe C.L. Recommendations on reporting requirements for flavonoids in research. Am. J. Clin. Nutr. 2015;101:1113–1125. doi: 10.3945/ajcn.113.071274. - DOI - PubMed