Betanin protects against diabetic retinal damage via the inhibition of NF-κB/NLRP3/VEGF axis: Insights from network pharmacology and experimental studies.

Diabetic retinopathy (DIR) is a predominant diabetic microvascular complication that may cause vision loss. Retinal inflammation and angiogenesis contribute largely to the neuronal degeneration in DIR. The current study is aiming to test the effect of oral betanin doses in protection from DIR in rats along with a network pharmacology study to investigate an assumption that betanin may inhibit nuclear factor-κ B (NF-κB). Three rat groups were assigned as vehicle, DIR, and DIR + Betanin 100 mg/kg. Molecular docking indicated the possible binding between betanin and NF-κB while the bioinformatic study highlighted a relation between this possible inhibition and suppression of NOD-like receptor pyrin domain-containing protein 3/vascular endothelial growth factor (NLRP3/VEGF) axis. The rat experimental study validated this assumption and indicated a protective effect for betanin on rat retinas as shown by routine hematoxylin and eosin staining (retinal thickness and ganglion cell count) and periodic acid-Schiff staining that was mediated through mitigating expression/protein level for of NF-κB, NLRP3, TNF-α, IL-6 and VEGF proteins. Immunohistochemistry showed that betanin was able to suppress retinal content of the glial fibrillary acidic protein (GFAP). In conclusion, the current study indicated that betanin was a good candidate for DIR in rats through suppression of the inflammatory cascade and may be suggested for diabetic patients if appropriated clinical studies will be available.