Protopanaxatriol ameliorates diabetic retinopathy by regulating mTOR/G6PD mediated pentose phosphate pathway.

In traditional Chinese medicine (TCM), Panax notoginseng and Panax notoginseng saponins (PNS) have been widely used to treat diabetic retinopathy (DR), but the material basis remains to be elucidated. This study aims to investigate the pharmacological effects and underlying mechanisms of protopanaxatriol (PPT), a main metabolite of PNS, in the treatment of DR. UPLC-MS/MS was employed to identify the metabolites of PNS in rats, and the metabolite PPT was detected in plasma, liver and intestinal contents of rats after oral administration of PNS. Different concentrations of PPT could significantly inhibit the proliferation, cell migration and tube formation of hRMECs induced by high-glucose in vitro and reduce the retinal vessel diameters of Tg (Fli1a: EGFP) zebrafish larvae, which were dilated by 130 mmol/L glucose in vivo. Cellular metabolomics revealed that PPT modulated the pentose phosphate pathway of hRMECs in high glucose. Further research indicates that PPT significantly reduced the G6PD activity and decreased the phosphorylation of mTOR in high glucose-induced hRMECs. In conclusion, PPT, a main metabolite of PNS, could effectively ameliorate DR by regulating the mTOR/G6PD-mediated pentose phosphate pathway, which may provide scientific data for elucidating the material basis of PNS in treating DR.