Ferulic acid attenuates high glucose-induced apoptosis in retinal pigment epithelium cells and protects retina in db/db mice

Abstract

Background Herein, we aimed to present evidence that Ferulic acid (FA), a phenolic acid, can alleviate high glucose (HG)-induced retinal pigment epithelium (RPE) cell apoptosis and protect retina in db/db mice. Methods ARPE-19 cells (a human RPE cell line) were divided into four groups: control group; HG group (30 mmol/L glucose); HG+FA group (30 mmol/L glucose and 10 mmol/L FA). Cell viability and apoptosis were detected using CCK-8 and Annexin-5 staining, respectively. Apoptosis-related markers including P53, BAX and Bcl2 were examined by RT-qPCR, western blot and immunohistochemistry. Totally, 30 male db/db mice were randomly divided into db/db group (5 ml/kg saline) and FA group (0.05 g/kg FA). After treatment for 2 months, retinal samples were subjected to hematoxylin and eosin (H&E) and Masson staining. Moreover, immunofluorescence was used to detect apoptosis-related markers. Blood samples were collected for measuring cholesterol, triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels. Results FA treatment markedly increased cell viability and suppressed cell apoptosis of ARPE-19 cells compared to the HG-exposed group. Furthermore, FA ameliorated the abnormal expression levels of P53, BAX and Bcl2 in HG-induced ARPE-19 cells. In animal models, FA attenuated pathological changes in the retina tissues of diabetic mice. Consistent with in vitro models, FA significantly ameliorated the expression of apoptosis-related markers in retina tissues. Biochemical test results showed that FA reduced hyperlipidemia in diabetic mice. Conclusion Our findings suggest that FA alleviates HG-induced apoptosis in RPE cells and protects retina in db/db mice, which can be associated with P53 and BAX inactivation and Bcl2 activation.

Exploring the protective effects of herbal monomers against diabetic retinopathy based on the regulation of autophagy and apoptosis: A review

“…[ 63 ] Due to FA treatment, BCL2 associated X (Bax) levels were reduced and B-cell lymphoma-2 (Bcl-2) levels decreased in ARPE-19 cells induced by high glucose, as well as p53 activation was inhibited. [ 64 ] In other words, FA inhibited HG-induced apoptosis of RPE cells through the P53/BAX/Bcl-2 pathway and ameliorated retinal tissue cell edema.…”

New Insights on Dietary Polyphenols for the Management of Oxidative Stress and Neuroinflammation in Diabetic Retinopathy

“…Zhu et al [ 127 ] investigated the anti-apoptotic effect of FA in RPE cells (ARPE-19) exposed to high glucose and its cytoprotective effects in the retina of db/db diabetic mice. Treatment with FA significantly increased cell viability and suppressed cell apoptosis in ARPE-19 cells compared with the untreated group.…”