Curcumol targets the FTO/MAFG-AS1 axis to alleviate diabetic retinopathy via epigenetic remodeling and nanodelivery-based microenvironment modulation

Table 1 Main molecular targets and mechanisms of action of curcumol

Molecular target	Normal function	Changes in DR	Regulatory effect of curcumol	Downstream pathological impact	Ref.
FTO protein	m6A demethylase; regulates RNA stability and expression	Abnormal expression under high-glucose conditions; significantly elevated in fibrovascular vitreous membranes of proliferative DR patients	Increases FTO expression, activating its demethylase activity	Stabilizes MAFG-AS1 expression, inhibits endothelial inflammation and vascular leakage	Rong et al[1]
MAFG-AS1	Long non-coding RNA involved in metabolism and inflammation regulation	Increased m6A modification and decreased stability under high-glucose conditions	Stabilizes MAFG-AS1 through FTO-mediated demethylation	Suppresses high glucose-induced endothelial proliferation, migration, and inflammation	Rong et al[1]
Histone lactylation	Epigenetic modification regulating gene expression	Lactate-mediated histone lactylation upregulates FTO expression	Possibly indirectly regulates FTO expression via modulation of histone lactylation	Forms a more complex epigenetic regulatory network, influencing retinal vascular integrity	Chen et al[6]
Inflammatory cytokines	Mediate immune responses and tissue repair	Elevated pro-inflammatory cytokines (TNF-α, IL-6), triggering chronic inflammation	Downregulates IκBα, cyclooxygenase-2, prostaglandin E2, and multiple interleukins	Reduces retinal inflammation, protecting retinal neurons and vascular function	Franzone et al[50]
Blood-retinal barrier components	Maintain homeostasis in the retinal microenvironment	Reduced cadherin and tight junction protein ZO-1 expression, impairing barrier function	Restores endothelial-specific cadherin and ZO-1 expression	Reduces vascular leakage, protecting retinal neurons from damage	Chen et al[6]

DR: Diabetic retinopathy; IL-6: Interleukin-6; m6A: N6-methyladenosine; TNF-α: Tumor necrosis factor-alpha; ZO-1: Zonula occludens-1.