Sanggenol L attenuates inflammation and apoptosis via Nrf2/PI3K/Akt signaling in retinal ganglion cells: an in vitro and in silico study on OGD/R-induced retinal ischemia-reperfusion injury.

Abstract

This study evaluates the protective effects of Sanggenol L (SL), a flavonoid from Morus alba root bark, against retinal ischemia/reperfusion injury (RI/RI)-induced retinal ganglion cell (RGC) damage in an oxygen and glucose deprivation/reoxygenation (OGD/R) model. SL (5-30 µM) significantly improved R28 cell viability, upregulated anti-apoptotic gene expression, and restored antioxidant status. Furthermore, SL reduced pro-inflammatory cytokines, lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), and pro-apoptotic gene expression in a dose-dependent manner. SL treatment (30 µM) activated the PI3K/Akt/Nrf2 signaling pathway, providing neuroprotection. In silico molecular docking revealed strong binding affinities between SL and key inflammatory and apoptotic markers (cyt-c, cleaved caspase-9, cleaved PARP, Nrf2, PI3K, Akt), suggesting its mechanism of action. These results indicate that SL may serve as a potential therapeutic agent for glaucomatous neurodegeneration by targeting oxidative stress, inflammation, and apoptosis via the PI3K/Akt/Nrf2 pathway.

Key Findings

• Sanggenol L (SL) significantly improved retinal ganglion cell viability and upregulated anti-apoptotic gene expression in an OGD/R model of retinal ischemia/reperfusion injury.
• SL reduced pro-inflammatory cytokines, oxidative stress markers (ROS, MDA), and pro-apoptotic gene expression in a dose-dependent manner.
• SL activated the PI3K/Akt/Nrf2 signaling pathway, providing neuroprotection, with molecular docking confirming strong binding to key inflammatory and apoptotic markers.

Clinical Significance

Citation

Xu Bing, Velu Periyannan, Fan Juneet al.. Sanggenol L attenuates inflammation and apoptosis via Nrf2/PI3K/Akt signaling in retinal ganglion cells: an in vitro and in silico study on OGD/R-induced retinal ischemia-reperfusion injury. 3 Biotech. 2026-Jun.