Potential therapeutic properties of natural products through the expression of heme oxygenase-1

Heme oxygenase-1 (HO-1) production is induced in many cell types in response to numerous stimuli, such as the presence of hemes and other oxidants, endotoxin, pro-inflammatory cytokines, or heavy metals, as well as inflammation, hypoxia, or hyperoxia. In addition, HO-1 and the subsequent metabolites of heme catabolism appear to play vital roles in the regulation of important biological responses, including inflammation, oxidative stress, cell survival, and cell proliferation. Thus, HO-1 production is observed in a number of disease states, such as brain disorders, inflammatory diseases, diabetes mellitus, and cancer. Various signaling molecules have been identified as being involved in the regulation of HO-1 expression, including the mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), nuclear transcription factor erythroid-2 related factor 2 (Nrf2), AP-1 family, PI3K/Akt, and Bach1 signaling pathways. Moreover, recent studies have focused on the identification of HO-1-regulating natural products and the investigation of the mechanisms underlying their biological effects against various types of diseases. The biological effects of HO-1-regulating natural products appear to be related to their ability to modulate their antioxidant activity, anti-inflammatory effects, cell survival, and cell proliferation. In addition, these natural products, such as flavonoids, chalcone, lignin, xanthone, etc., have been shown to mediate their beneficial effects via HO-1 expression. These summarized reports strongly suggest that induction of HO-1 expression by natural products may be a promising therapeutic signaling target for the treatment of various human diseases.