The phytochemical bergenin as an adjunct immunotherapy for tuberculosis in mice

Abstract

The widespread availability and use of modern synthetic therapeutic agents have led to a massive decline in ethnomedical therapies. However, these synthetic agents often possess toxicity leading to various adverse effects. For instance, anti-tubercular treatment (ATT) is toxic, lengthy, and severely impairs host immunity, resulting in posttreatment vulnerability to reinfection and reactivation of tuberculosis (TB). Incomplete ATT enhances the risk for the generation of multidrug-or extensively drug-resistant (MDR or XDR, respectively) variants of Mycobacterium tuberculosis (M. tb), the TB-causing microbe. Therefore, a new therapeutic approach that minimizes these risks is urgently needed to combat this deadly disease and prevent future TB epidemics. Previously, we have shown that the phytochemical bergenin induces T helper 1 (Th1)-and Th17 cellbased protective immune responses and potently inhibits mycobacterial growth in a murine model of M. tb infection, suggesting bergenin as a potential adjunct agent to TB therapy. Here, we combined ATT therapy with bergenin and found that this combination reduces immune impairment and the length of treatment in mice. We observed that co-treatment with the anti-TB drug isoniazid and bergenin produces additive effects and significantly reduces bacterial loads compared with isoniazid treatment alone. The bergenin co-treatment also reduced isoniazid-induced immune impairment; promoted long-lasting, antigen-specific central memory T cell responses; and acted as a self-propelled vaccine. Of note, bergenin treatment significantly reduced the bacterial burden of a multidrug-resistant TB strain. These observations suggest that bergenin is a potent immunomodulatory agent that could be further explored as a potential adjunct to TB therapy. cro ARTICLE

Bergenin as a Novel Urate-Lowering Therapeutic Strategy for Hyperuricemia

“…Bergenin is the C-glucoside of 4- O -methyl gallic acid and can be found in several medicinal plants, including Bergenia crassifolia and Corylopsis spicata ( Liang et al, 2017 ). Bergenin has been reported to have multiple biological activities, including antiarthritic ( Jain et al, 2014 ; Singh et al, 2017 ), immunomodulatory ( Wang et al, 2017 ; Kumar et al, 2019 ), antidiabetic ( Veerapur et al, 2012 ), osteogenic ( Hou et al, 2019 ), neuroprotective ( Barai et al, 2019 ; Ji et al, 2019 ), and wound-healing effects ( Mukherjee et al, 2013 ). Wang et al (2017) showed that bergenin attenuated colitis by activating the peroxisome proliferator-activated receptor (PPAR) γ.…”

Potentiation of rifampin activity in a mouse model of tuberculosis by activation of host transcription factor EB

“…To date the evidence is limited that any host-targeting agent reproducibly reduces CFU of Mtb in otherwise genetically and pharmacologically unmanipulated animals infected with virulent Mtb when the HDT is administered after the onset of disease and as the sole intervention. The current portfolio of candidates for HDT of TB [ 4 – 7 ] includes candidates that were nominated based on treating mice infected with mycobacteria of a less virulent form than wild type Mtb [ 8 , 9 ], treating before the onset of disease [ 8 , 10 ], treating after knock out of a key element of immunity [ 11 ], or dosing with another agent that deviates the immune response [ 11 ], while others are effective against some Mtb strains and not others [ 12 ]. In some cases, the reduction in Mtb CFU was significant only after censoring some results [ 13 ], amounted to only ~0.2 log 10 [ 14 , 15 ], was reported from single experiments [ 13 , 15 ], or was not independently reproducible [ 16 , 17 ].…”

Potent anti‐mycobacterial and immunomodulatory activity of some bioactive molecules of Indian ethnomedicinal plants that have the potential to enter in TB management

“…Surprisingly, they found that bergenin reduces the immune impairment of TB and thereby clears the bacteria fast in combination therapy with INH and reduces the bacterial burden more than 4 log in compared to 1 log reduction achieved by either INH or bergenin individually (Kumar et al . 2019). Moreover, bergenin also reverts the activation‐induced cell death of TB‐antigen‐specific T cells by isoniazid and provides the animals’ long‐term host protective immune response, which might be helpful for the development of herd immunity (Kumar et al .…”

“…Moreover, bergenin also reverts the activation‐induced cell death of TB‐antigen‐specific T cells by isoniazid and provides the animals’ long‐term host protective immune response, which might be helpful for the development of herd immunity (Kumar et al . 2019). Therefore, from all the ethnomedicinal work on S. robusta , it is proved that bergenin one of the bioactive molecules could be used as an immunomodulatory adjunct therapy with normal conventional TB treatment (Fig.…”