The potential role of phytochemicals in non-alcoholic fatty liver disease (NAFLD) through modulation of forkhead box O1 (FOXO1) transcription factor signaling pathways; a review

Literature evidences reveal that natural compounds are potential candidates for ameliorating obesity associated non-alcoholic fatty liver disease (NAFLD) by targeting forkhead box O1 (FOXO1). FOXO has dual and complex role in regulating both increase and decrease in lipids accumulation in hepatocytes and adipose tissues (AT) at different stages of NAFLD. In insulin resistance (IR), FOXO1 is constitutively expressed, resulting in increased hepatic glucose output and lipids metabolism irregularity. The studies on different phytochemicals indicate that dysregulation of FOXO1 causes disturbance in cellular nutrients homeostasis. The current review communicates and evaluates certain phytochemicals through different search engines, targeting FOXO1 and its downstream cellular pathways, to find lead compounds as potential therapeutic agents for treating NAFLD and related metabolic disorders. The findings of this review confirm that polyphenols, alkaloids, terpenoids and anthocyanins are capable of modulating FOXO1 and related signaling pathways and they are potential therapeutic agents for NAFLD and related complications.

现有文献研究证实，天然化合物可通过靶向叉头框蛋白O1（forkhead box O1, FOXO1），成为缓解肥胖相关非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）的潜在候选物质。叉头框蛋白O1（FOXO1）在非酒精性脂肪性肝病的不同病程阶段，对肝细胞与脂肪组织（adipose tissues, AT）内的脂质积累兼具双向且复杂的调控作用，既可促进脂质堆积，也可抑制其积累。在胰岛素抵抗（insulin resistance, IR）状态下，FOXO1会出现持续性异常表达，进而导致肝脏葡萄糖输出增加以及脂质代谢紊乱。针对各类植物化学物（phytochemicals）的相关研究显示，FOXO1的表达失调会破坏细胞营养稳态。本综述通过多搜索引擎检索相关文献，对靶向FOXO1及其下游细胞通路的若干植物化学物进行了系统梳理与评估，旨在筛选可用于治疗非酒精性脂肪性肝病及相关代谢紊乱的潜在先导治疗化合物。本综述的研究结果证实，多酚类（polyphenols）、生物碱（alkaloids）、萜类（terpenoids）以及花青素（anthocyanins）可调控FOXO1及其相关信号通路，是治疗非酒精性脂肪性肝病及其并发症的潜在治疗药物。