The phytochemical bergenin as an adjunct immunotherapy for tuberculosis in mice

Santosh Kumar, Chetan Sharma, Sandeep Rai Kaushik, Ankur Kulshreshtha, Shivam Chaturvedi, Ranjan Kumar Nanda, Ashima Bhaskar, Debprasad Chattopadhyay, Gobardhan Das, Ved Prakash Dwivedi

Research output: Contribution to journalArticle

4 Scopus citations

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(MDRor 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.

Original languageEnglish (US)
Pages (from-to)8555-8563
Number of pages9
JournalJournal of Biological Chemistry
Volume294
Issue number21
DOIs
StatePublished - May 24 2019

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The phytochemical bergenin as an adjunct immunotherapy for tuberculosis in mice'. Together they form a unique fingerprint.

Cite this