Abstract

Glaucoma is an irreversible, blinding eye disease with limited treatment options. Puerarin has anti-inflammatory and neuroprotective effects; however, its glaucoma-related mechanisms remain unclear. This study aimed to explore whether puerarin eases inflammation in a rat model of glaucoma and protects the optic nerve by inhibiting NF-κB pathway. Differentially expressed genes (DEGs) in glaucoma were screened from the GEO database (GSE138125), and potential targets of puerarin were identified and verified. A rat model of glaucoma was established, and the animals were divided into multiple groups. Intraocular pressure, tissue pathology, levels of apoptosis-related proteins, NF-κB-related proteins, and inflammatory factors were measured. The online database analysis screened 2582 DEGs, among which NF-κB1 was the core target of puerarin (binding energy, -5.12 kcal/mol). In vivo animal experiments confirmed that puerarin significantly reduced the intraocular pressure in glaucomatous rats, improved retinal structural damage, and inhibited cell apoptosis (downregulated Bax/Cleaved-Caspase-3 levels and upregulated Bcl-2 levels). In terms of mechanism verification, puerarin inhibited pro-inflammatory factors (IL-6/TNF-α/IL-1β), upregulated levels of the anti-inflammatory factor IL-10, and blocked the activation of the NF-κB pathway (decreased p-IκBα/p-NF-κB levels). Lipopolysaccharide reversed the above-mentioned protective effects of puerarin, confirming its dependence on the NF-κB pathway. Puerarin alleviates the inflammatory response and retinal ganglion cell apoptosis by targeting and inhibiting the NF-κB signaling pathway, providing a new potential strategy for the treatment of glaucoma.