Therapeutic Effect and Mechanism of Keluoxin on Diabetic Retinopathy by Untargeted Metabolomics Analysis Based On UPLC-MS/MS |Biomedgrid

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and one of the leading causes of blindness worldwide. Keluoxin (KLX) is a Chinese patent medicine, can effectively improve DR, but its mechanism is not yet clear. This study aims to reveal the mechanism of KLX effect on DR through untargeted metabolomics. The diabetic retinopathy model was established in db/db mice, and the DR development process of the mice and the intervention effect of KLX on DR were evaluated by body weight, blood glucose, electroretinogram and histopathology. UPLC-MS/MS was used for urine metabolomic analysis, and Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) were used to identify DR urine biomarkers. Pathway analysis and literature reveal the mechanism by which KLX interferes with DR. KLX can significantly reduce body weight and blood glucose in db/db mice, improve retinal function and structure in db/db mice, and has an effective DR improvement effect. The results of urine metabolomics analysis showed that KLX could regulate the metabolic profile of db/db mice, making it tend to be close to the control group. A total of 69 DR urine biomarkers were identified, of which 50 were recalled by KLX. It was found that the KLX improved DR may be related to the regulation of tryptophan metabolism and arachidonic acid metabolism. We discuss the potential mechanism of KLX affects DR, which provides a scientific basis for the application of KLX and the treatment of DR.