Targeting metabolic syndrome with phytochemicals: Focus on the role of molecular chaperones and hormesis in drug discovery.

Adaptive cellular stress response confers stress tolerance against inflammatory and metabolic disorders. In response to metabolic stress, the key mediator of cellular adaptation and tolerance is a class of molecules called the molecular chaperones (MCs). MCs are highly conserved molecules that play critical role in maintaining protein stability and functionality. Hormesis in this context is a unique adaptation mechanism where a low dose of a stressor (which is toxic at high dose) confers a stress-resistant adaptive cellular phenotype. Hormesis can be observed at different level of biological organization at various measurable endpoints. The MCs are believed to play a key role in adaptation during hormesis. Several phytochemicals are known for their hormetic response and are called phytochemical hormetins. The role of phytochemical-mediated hormesis on the adaptive cellular processes is proposed as a potential therapeutic approach to target inflammation associated with metabolic syndrome. However, the screening of phytochemical hormetins would require a paradigm shift in the methods currently used in drug discovery.