Potential immunomodulatory effect of allelochemical juglone in mice vaccinated with BCG

Juglone, a naphthoquinone is a known phytotoxic and cytotoxic allelochemical. Various anticancer studies suggest that pharmacological ROS insult and enzymes inhibited by juglone could be of therapeutic utility. In this study, we show that juglone induces immunomodulation in BCG-vaccinated mice. We have shown that juglone treatment leads to the generation of Th1 cytokines which develops an M1 phenotype in splenic macrophages. These findings were supported by a decrease in Treg population in BCG-vaccinated mice treated with juglone. Additionally, we observed juglone significantly increases CD8⁺ and T-helper memory population in BCG-vaccinated mice under immunomodulation. Further, BCG-challenge test showed that juglone enhances effector immune functions. Our finding was demonstrated by estimating ex-vivo Th1 and Th2 cytokines, flow cytometric analysis of Treg, T-helper memory, and CD8⁺ cells and determining serum IgG2a/IgG1 titer shift in BCG-vaccinated animals treated with juglone. Collectively, our findings provide evidence that juglone may act as immunomodulator when used at a low dose, metronomically.