Abstract

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection.

Highlights

  • Nontuberculous mycobacteria (NTM) are organisms present in water, soil, and throughout our environment [1,2]

  • M1 macrophages, induced by the Th1-dependent cytokine interferon (IFN)-γ, play an important role in the elimination of various pathogens including Mycobacterium avium complex (MAC) [8]. They upregulate the expression of proinflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor (TNF)-α) and via activation of inducible nitric oxide (NO) synthase are able to secrete NO, a free radical that is toxic to bacteria and other pathogens

  • We have demonstrated that the plasma oxygen radical absorbance capacity (ORAC) value of rats fed the non-extractable fraction of persimmon fruit, which contains condensed tannin, was higher than the control diet group

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Summary

Introduction

Nontuberculous mycobacteria (NTM) are organisms present in water, soil, and throughout our environment [1,2]. NTM, including Mycobacterium avium complex (MAC), causes chronic pulmonary infection, especially in immune-deficient people, the factors involved in MAC pathogenesis are not identified. These organisms are more resistant to antibiotics than Mycobacterium tuberculosis, and an effective treatment has yet to be established. M1 macrophages, induced by the Th1-dependent cytokine interferon (IFN)-γ, play an important role in the elimination of various pathogens including MAC [8]. They upregulate the expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and via activation of inducible NO synthase (iNOS) are able to secrete NO, a free radical that is toxic to bacteria and other pathogens. They are deeply involved in inflammation and granuloma formation, which play critical roles in protection against MAC [4]

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