The potential protective role of carotenoids from saffron: A focus on endoplasmic reticulum stress-related organ damage.

The anticancer, antioxidant, and immunomodulatory properties of carotenoids from saffron or apocarotenoids (e.g., crocin, safranal, crocetin, and picrocrocin) have prompted research into their benefits. Apocarotenoids seem to be effective compound for the treatment of chronic diseases, such as neurodegenerative, cardiovascular, cancer, respiratory, and metabolic disorders. Endoplasmic reticulum (ER) is an essential organelle found in the cytoplasm of eukaryotic cells that participates in the biosynthesis of proteins, lipids, and steroid hormones. Given the role of the ER in the regulation of several fundamental biological processes, including metabolic pathways and immune responses, aberrant ER function can have a significant influence on these vital processes and result in serious pathological consequences. Exposure of cell to adverse environmental challenges, such as toxic agents, ischemia, and so on, causes accumulation of unfolded or misfolded proteins in the ER lumen, also called ER stress. There is a growing evidence to suggest that ER disturbance in the form of oxidative/nitrosative stress and subsequent apoptotic cell death plays major roles in the pathogenesis of many human diseases, including cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, and liver diseases. Apocarotenoids with their unique properties can modulate ER stress through PERK/eIF2α/ATF4/CHOP (protein kinase R (PKR)-like ER kinase/eukaryotic initiation factor 2α/activating transcription factor 4/C/EBP /homologous protein) and X-Box Binding Protein 1/activating transcription factor 6 (XBP1/ATF6) pathways. In addition, they suppress apoptosis through inhibition of endoplasmic and mitochondrial-dependent caspase cascade and can stimulate SIRT1 (silent information regulator 1) and Nrf2 (nuclear factor erythroid 2-related factor 2) expression, thereby leading to protection against oxidative stress. This review summarizes the potential benefits of apocarotenoids in various ER-stress-related disorders.