Mirzavi Farshad, Rajabian Arezoo, Hosseini Hossein
Cardiovascular Diseases Research Center Birjand University of Medical Sciences Birjand Iran.
Neuroscience Research Center Mashhad University of Medical Sciences Mashhad Iran.
Food Sci Nutr. 2024 Jun 21;12(9):6108-6122. doi: 10.1002/fsn3.4289. eCollection 2024 Sep.
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.
藏红花类胡萝卜素或脱辅基类胡萝卜素（如藏红花素、藏红花醛、藏红花酸和苦藏花素）的抗癌、抗氧化和免疫调节特性促使人们对其益处进行研究。脱辅基类胡萝卜素似乎是治疗慢性疾病（如神经退行性疾病、心血管疾病、癌症、呼吸系统疾病和代谢紊乱）的有效化合物。内质网（ER）是真核细胞细胞质中发现的一种重要细胞器，参与蛋白质、脂质和类固醇激素的生物合成。鉴于内质网在调节包括代谢途径和免疫反应在内的几个基本生物学过程中的作用，内质网功能异常会对这些重要过程产生重大影响，并导致严重的病理后果。细胞暴露于不利的环境挑战（如有毒物质、缺血等）会导致内质网腔中未折叠或错误折叠的蛋白质积累，也称为内质网应激。越来越多的证据表明，氧化/亚硝化应激形式的内质网紊乱以及随后的凋亡性细胞死亡在许多人类疾病（包括心血管疾病、糖尿病、神经退行性疾病和肝脏疾病）的发病机制中起主要作用。具有独特性质的脱辅基类胡萝卜素可以通过PERK/eIF2α/ATF4/CHOP（蛋白激酶R（PKR）样内质网激酶/真核起始因子2α/激活转录因子4/C/EBP同源蛋白）和X-Box结合蛋白1/激活转录因子6（XBP1/ATF6）途径调节内质网应激。此外，它们通过抑制内质网和线粒体依赖性半胱天冬酶级联反应来抑制细胞凋亡，并可以刺激SIRT1（沉默信息调节因子1）和Nrf2（核因子红细胞2相关因子2）的表达，从而导致对氧化应激的保护。本综述总结了脱辅基类胡萝卜素在各种内质网应激相关疾病中的潜在益处。
