Therapeutic roles of heme oxygenase-1 in metabolic diseases: curcumin and resveratrol analogues as possible inducers of heme oxygenase-1

Abstract

Metabolic diseases, such as insulin resistance, type II diabetes, and obesity, are associated with a low-grade chronic inflammation (inflammatory stress), oxidative stress, and endoplasmic reticulum (ER) stress. Because the integration of these stresses is critical to the pathogenesis of metabolic diseases, agents and cellular molecules that can modulate these stress responses are emerging as potential targets for intervention and treatment of metabolic diseases. It has been recognized that heme oxygenase-1 (HO-1) plays an important role in cellular protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic effects, HO-1 has been suggested to play important roles in pathogenesis of metabolic diseases. In the present review, we will explore our current understanding of the protective mechanisms of HO-1 in metabolic diseases and present some emerging therapeutic options for HO-1 expression in treating metabolic diseases, together with the therapeutic potential of curcumin and resveratrol analogues that have their ability to induce HO-1 expression.

Figure 1

Therapeutic targets of HO-1 during pathogenesis of metabolic diseases. Metabolic diseases, such as CVD, T2D, and obesity, frequently arise from defects among coordinated actions of multiple tissues. Cells in a tissue may be exposed to oxidative stress generated mainly by mitochondria, inflammatory stress initiated probably by saturated FA-TLR4 interaction, and ER stress triggered by inflammatory and oxidative stresses, and these stresses, when prolonged, may amplify and integrate with each other. The integration of advanced stresses may cause one or more of metabolic diseases. HO-1 expression may reduce oxidative stress, inflammatory stress, and ER stress, thereby exerting therapeutic actions.

Figure 2

Chemical structures of Cur and Res analogues.