Poria acid alleviates oxidative damage in mice with dry age-related macular degeneration by activating the Nrf2/HO-1 signaling pathway

Abstract

Background Poria acid (PA) extracted from the traditional Chinese medicinal herb Poria cocos (P cocos) is reported to protect organs such as the liver and lungs from damage. However, its effect on dry age-related macular degeneration (AMD) has not been reported. This research is to investigate the influence of PA on oxidative stress of the retina in vivo and in vitro. Methods In vitro, the viability of ARPE-19 cells was measured by the MTT. The apoptosis of the cells was detected by Flow cytometry and the expression of Caspase-3, Bax, and Bcl2. The oxidative stress level was evaluated by observing the production of reactive oxygen species (ROS) in vitro and superoxide dismutase (SOD), CAT, and GSH-px by ELISA in mice serum. The AMD model was induced by intravenous injection of sodium iodide (SI) through the tail vein of mice. The structure and the apoptosis of the mouse retina were monitored by optical coherence tomography (OCT), H&E, and TUNEL staining. The regulatory oxidative factor NRF2 and HO-1 were determined by fluorescence staining. ML385 and ZnPP were used for the exploration of the protective mechanism of PA. Results H2O2 decreased the cell viability of RPE cells, and was recovered after PA administration, which was shown to reduce the cell apoptosis rate as well as the expression of Bax, caspase-3, and the production of ROS. In vivo, the thinning of the retina and the apoptosis rate in the retina tissue of mice caused by the injection of SI is reversed by the treatment of PA. further, the PA administration caused translocation of Nrf2 and increased the expression of HO-1, and the application of their inhibitors inhibit the effect. Conclusion PA protects retinal pigment epithelial (RPE) cells from oxidative stress and apoptosis by activating the NRF2/HO-1 pathway and prevents retinal damage by halting the progression of retinal thinning in mice, which indicating its clinical therapeutic potential in treating AMD.