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 cell-based 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.