Kaempferol ameliorates oxidative stress injury in the retina through activating the PI3K/AKT/mTOR signaling pathway

Objective To investigate the mechanism of kaempferol in alleviating retinal oxidative stress injury. Methods ARPE-19 cells were treated with H₂O₂ to establish an in vitro model of retinal oxidative stress injury. The cell viability was assessed by CCK-8 assay. The apoptosis was detected by flow cytometry. Twenty-five male SD rats were randomly divided into five groups: a control group, a model group, a low-dose (12.5 mg/kg) kaempferol group, a medium-dose (25 mg/kg) kaempferol group and a high-dose (50 mg/kg) kaempferol group. Rats in the control group were kept normally, while those in the model and treatment groups were subject to acute retinal ischemia/reperfusion injury to construct a model of retinal oxidative stress injury. The intracellular activities of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected, the structural integrity of the retina was observed by H-E staining. The expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay (ELISA). The expression of apoptotic autophagy and the effect of PI3K/AKT/mTOR signaling pathway were evaluated by Western blot. Results In vitro cellular experiments showed that kaempferol significantly increased the viability and decreased the apoptosis of ARPE-19 cells induced by oxidative stress, compared with the control group (P＜0.05). In vivo experiments showed that compared with the model group, kaempferol attenuated retinal oxidative stress injury; significantly decreased MDA expression and elevated SOD expression (P＜0.05); significantly decreased the secretion of vascular endothelial growth factor (VEGF) and γ-interferon (IFN-γ) and increased the secretion of interleukin-10 (IL-10) (P＜0.05); and significantly enhanced the protein expression of B cell lymphoma/leukaemia-2 (BCL-2), microtubule-associated protein 1A/1B-light chain 3 (LC3), phosphatidylinositol 3 kinase (PI3K), phosphorylated target of rapamycin mechanism (p-mTOR) and phosphorylated serine/threonine kinase (p-AKT) and inhibited the protein expression of the antibody to the Bcl-2 cognate structural domain protein 1 (Beclin1) (P＜0.05). Conclusions Kaempferol attenuates retinal oxidative stress injury by activating the PI3K/AKT/mTOR signaling pathway.