Integration of UPLC-Q-Exactive MS/MS and in vivo studies to investigate the chemical composition and anti-diabetic nephropathy effects of polarity-based extracts from potentillae discoloris herba.

Diabetic nephropathy (DN), a common and severe microvascular complication of type 2 diabetes mellitus, is characterized by lesions in the glomeruli and renal tubules. The various components of Potentillae Discoloris Herba (PDH) exhibit pharmacological activities, including anti-inflammatory and hypoglycemic effects. However, research on its chemical constituents and therapeutic potential for DN remains limited. This study aimed to investigate the chemical constituents of PDH using UPLC-Q-Exactive MS/MS, determine their distribution among different solvent-extracted fractions, and identify the key bioactive fractions and compounds responsible for hypoglycemic and renoprotective effects in DN. The ethanol extract of PDH was sequentially fractionated into petroleum ether, ethyl acetate, n-butanol, and aqueous fractions, with UPLC-MS/MS analysis revealing 90 compounds, primarily phenolic acids, flavonoids, and triterpenoids. In a DN rat model induced by high-fat/high-sugar diet and streptozotocin, the ethyl acetate fraction demonstrated rich chemical diversity and promising therapeutic effects, including reduced fasting blood glucose, improved lipid metabolism, attenuated renal dysfunction, and alleviated histopathological damage. Systematic phytochemical analysis demonstrated that phenolic acids and flavonoids are likely the key bioactive constituents underlying PDH's antidiabetic and renal protective properties. These findings enhance the understanding of PDH's chemical composition and pharmacological potential in DN treatment.