Integrative experimental and computational analysis of a bioactivity guided fraction of Potentilla fulgens targeting oxidative stress and inflammatory pathways in diabetic neuropathy

Diabetic neuropathy (DN), driven by oxidative stress and inflammation, was investigated for its therapeutic modulation by a column derived bioactive fraction of Potentilla fulgens (PFCF3) using integrated in vitro, in vivo and computational methods. Bioactivity guided fractionation identified PFCF3 as the most potent antioxidant and anti-inflammatory fraction. In streptozotocin-induced DN rats (50 mg/kg, i.p.), oral PFCF3 reduced plasma glucose, restored body weight and reduced hyperalgesia, allodynia and thermal hypersensitivity. PFCF3 enhanced GSH, SOD and catalase levels while reducing lipid peroxidation and nitric oxide. ELISA analysis suggested upregulation of Nrf2 and suppression of NF-κB and IL-6, with improved sciatic nerve architecture. LC–MS identified 18 major phytoconstituents, while catechin and epicatechin showed notable binding affinities towards inflammatory targets in silico. HPLC analysis further confirmed enrichment of epicatechin in PFCF3. These findings suggest promising neuroprotective potential of PFCF3 against DN.