Salidroside ameliorates diabetic retinopathy and Müller cell inflammation via the PI3K/Akt/GSK-3β/NF-𝜅B pathway.

Purpose: To determine whether salidroside (SAL) modulates inflammatory cytokines in rat retinal Müller cells (rMC-1) in a hyperglycemic environment by investigating the anti-inflammatory mechanisms of SAL in vitro and in vivo. Methods: A streptozotocin (STZ)-induced diabetic rat model was established to examine the effects of SAL using hematoxylin and eosin (H&E) staining and immunohistochemistry. rMC-1 cells were grown in 50 mM of high-glucose medium. These simulated diabetic conditions were used to evaluate the anti-inflammatory effects of SAL using a Cell Counting Kit-8 (CCK-8) assay, immunofluorescence staining, western blotting, and real-time polymerase chain reaction (qRT‒PCR). H&E staining was used to analyze the number of ganglion cells in the retina. rMC-1 lysates were processed for qRT‒PCR to measure the steady-state mRNA expression levels of inflammatory markers, such as interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 1β (IL-1β). Western blot analysis and immunofluorescence staining were performed to determine the levels of these inflammatory markers. Results: Our study showed that SAL reversed retinal ganglion cell loss and attenuated nuclear factor kappa B (NF-𝜅B) p65 translocation to the nucleus in STZ-induced diabetic rats. Incubating rMC-1 in different concentrations of SAL for 24 to 48 h affected cell viability. Furthermore, SAL treatment significantly decreased the protein levels of IL-6, TNF-α, and IL-1β compared with those in cells cultured in high glucose (HG). The mRNA expression levels of IL-6 and IL-1β were considerably reduced after SAL treatment, whereas the mRNA expression levels of IL-10 were significantly increased. Interestingly, the beneficial effects of SAL on HG-treated rMC-1 cells were abolished by the PI3K inhibitor LY294002. Conclusions: These results indicate that SAL treatment reduces cytokine activation in cultured rMC-1. Furthermore, SAL prevents diabetic retinopathy (DR), in part, by modulating the PI3K/Akt/GSK-3β/NF-kB pathway to inhibit Müller cell activation. Thus, SAL is expected to be a potential agent for ameliorating the progression of DR.