Phytochemicals targeting NAFLD through modulating the dual function of forkhead box O1 (FOXO1) transcription factor signaling pathways.
Usman SabirHafiz Muhammad Irfannull AlamgeerIhtisham UmerZahid Rasul NiaziHafiz Muhammad Mazhar AsjadPublished in: Naunyn-Schmiedeberg's archives of pharmacology (2022)
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.
Keyphrases
- transcription factor
- signaling pathway
- insulin resistance
- pi k akt
- oxidative stress
- dna binding
- metabolic syndrome
- type diabetes
- genome wide identification
- high fat diet induced
- adipose tissue
- induced apoptosis
- epithelial mesenchymal transition
- weight loss
- systematic review
- dna damage
- cell death
- weight gain
- climate change
- skeletal muscle
- polycystic ovary syndrome
- high fat diet
- cell proliferation
- cancer therapy
- risk assessment
- body mass index
- physical activity
- heavy metals
- drug induced
- drug delivery
- human health
- glycemic control
- diabetic rats