Effect of the ethyl acetate extract of Sophora flavescens Aiton on diabetic retinopathy based on untargeted retinal metabolomics

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1198; p. 123233
• Main Authors: Luo, Yun, Zhao, Kairui, Li, Zhaocheng, Gao, Yanping, Lin, Minling, Li, Yadi, Wang, Shumei, Liu, Yi, Chen, Lei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.05.2022
• Subjects: Acetates; Animals; Diabetes Mellitus; Diabetic retinopathy; Diabetic Retinopathy - drug therapy; Flavonoids - chemistry; Flavonoids - pharmacology; Mechanism; Metabolomics - methods; Pharmacodynamics; Plant Extracts - chemistry; Rats; Retina; Retinal metabolomics; Sophora - chemistry; Sophora flavescens Aiton; TMAO; Diabetic retinopathy; AADC; IPL; INL; TUDCA; IPP; FBG; OPL; ONL; Mechanism; DR; LPS; SFE; TUNEL; BW; AOD; STZ; LRAT; Retinal metabolomics; EIC; EtOAc; CD; Pharmacodynamics; AH; OPLS-DA; Sophora flavescens Aiton; PCA; GCL; RPE-65; BRB; NOS; HRMECs; ELISA; TCM
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2022.123233

[Display omitted] •To evaluate the pharmacodynamic effects of SFE against streptozotocin-induced DR rats from multiple levels for the first time.•To study the distribution of flavonoids of Sophora flavescens Aiton in rat’s aqueous humor and retina by UHPLC-MS.•To explore the mechanism of SFE against on DR based on untargeted retinal metabolomics.•To elucidate the effects, material basis and treatment mechanism of SFE on DR systematically. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and a leading cause of vision impairment and blindness, which lacks effective diagnostic measures and therapeutic options. Sophora flavescens Aiton or “Kushen” is a traditional Chinese medicine used since ancient times, either alone or in combination, to clear heat, dampness, and tearing, and to treat ocular diseases and improve eyesight. Additionally, the flavonoids of Sophora flavescens Aiton extracted using ethyl acetate (EtOAc) (SFE) is effective in managing diabetes and diabetic vascular complications. In this study, we explored the pharmacodynamic effects and material basis of action of SFE on DR for the first time and elucidated the mechanism based on untargeted retinal metabolomics. Results from the pharmacodynamic studies showed that SFE could reduce blood glucose levels in rats, regulate serum lipopolysaccharide, tauroursodeoxycholic acid, and trimethylamine oxide levels, and significantly improve the structure of retina in rats with DR. Moreover, SFE could protect the blood-retinal barrier, reduce angiogenesis and capillary formation, and inhibit retinal nerve cell apoptosis. A total of 13 compounds were identified in the aqueous humor and retina, which were dihydroflavonoid, isoflavonoid, pterostane flavonoid, chalcone, and dihydroflavonol derivatives. In addition, 39 differential metabolites were screened based on retinal metabolomics data and 23 were found to be affected by SFE, indicating its anti-DR effect by regulating the synthetic metabolic pathways, including lactose, bile acid, glycerophospholipid, arginine, purine, and pyrimidine metabolism pathways. Collectively, our findings elucidated the effects, material basis, and treatment mechanism of SFE on DR systematically and could lay the foundation for promoting the clinical application of Sophora flavescens Aiton.