Department of Pharmacology, College of Pharmacy, University of Sargodha, Sargodha, Pakistan.
Punjab University College of Pharmacy, University of the Punjab Lahore, Lahore, Pakistan.
Naunyn Schmiedebergs Arch Pharmacol. 2022 Jul;395(7):741-755. doi: 10.1007/s00210-022-02234-2. Epub 2022 Mar 31.
Literature evidence reveals that natural compounds are potential candidates for ameliorating obesity-associated non-alcoholic fatty liver disease (NAFLD) by targeting forkhead box O1 (FOXO1) transcription factor. FOXO1 has a dual and complex role in regulating both increase and decrease in lipid accumulation in hepatocytes and adipose tissues (AT) at different stages of NAFLD. In insulin resistance (IR), it is constitutively expressed, resulting in increased hepatic glucose output and lipid metabolism irregularity. The studies on different phytochemicals indicate that dysregulation of FOXO1 causes disturbance in cellular nutrients homeostasis, and the natural entities have an enduring impact on the mitigation of these abnormalities. 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, flavonoids, alkaloids, terpenoids, and anthocyanins are capable of modulating FOXO1 and associated signaling pathways, and they are potential therapeutic agents for NAFLD and related complications. HIGHLIGHTS: • FOXO1 has the potential to be targeted by novel drugs from natural sources for the treatment of NAFLD and obesity. • FOXO1 regulates cellular autophagy, inflammation, oxidative stress, and lipogenesis through alternative mechanisms. • Phytochemicals treat NAFLD by acting on FOXO1 or SREBP1c and PPARγ transcription factor signaling pathways.
文献证据表明，天然化合物是通过靶向叉头框 O1（FOXO1）转录因子改善肥胖相关非酒精性脂肪性肝病（NAFLD）的潜在候选药物。FOXO1 在调节肝细胞和脂肪组织（AT）中脂质积累的增加和减少方面具有双重且复杂的作用，在 NAFLD 的不同阶段。在胰岛素抵抗（IR）中，它持续表达，导致肝葡萄糖输出增加和脂质代谢异常。对不同植物化学物质的研究表明，FOXO1 的失调导致细胞营养物质稳态紊乱，天然实体对减轻这些异常具有持久影响。本综述通过不同的搜索引擎传达和评估某些植物化学物质，针对 FOXO1 及其下游细胞途径，以寻找潜在的治疗药物作为治疗 NAFLD 和相关代谢紊乱的潜在治疗药物。本综述的研究结果证实，多酚、类黄酮、生物碱、萜类化合物和花青素能够调节 FOXO1 及其相关信号通路，是治疗 NAFLD 和相关并发症的潜在治疗药物。要点： • 新型药物有可能从天然来源靶向 FOXO1 治疗 NAFLD 和肥胖症。 • FOXO1 通过不同的机制调节细胞自噬、炎症、氧化应激和脂肪生成。 • 植物化学物质通过作用于 FOXO1 或 SREBP1c 和 PPARγ 转录因子信号通路来治疗 NAFLD。
