Extraction optimization of <i>Phellinus baumii</i> residue polysaccharides and investigation of their anti-aging effects <i>via</i> regulation of Keap1/Nrf2/HO-1 signaling pathway

Population aging posed an increasing burden on global health, highlighting the demand for safe and effective anti-aging therapeutics. This study was designed to optimize the extraction of <i>Phellinus baumii</i> residue polysaccharide (PBRP), a pyran-type polysaccharide linked by β-glycosidic bonds, by a quadratic regression model based on the Box-Behnken design (BBD) within the response surface methodology (RSM). Additionally, the anti-aging effects were systematically evaluated in a D-galactose-induced aging mouse model, with a focus on elucidating mechanism associated with the Keap1/Nrf2/HO-1 signaling pathway. By analyzing the regression equations and model graphs, the optimum conditions were conveniently set at extraction cycles of 2, extraction temperature of 83 °C, and ethanol concentration of 85%, yielding an experimental extraction efficiency of 2.57 ± 0.05%. Furthermore, the physiological and molecular biological evidences from both <i>in vitro</i> and <i>in vivo</i> analysis demonstrated that PBRP could activate the Keap1/Nrf2/HO-1 signaling pathway, thereby mitigating oxidative stress and ameliorating the aging-associated properties. These findings provided novel insights into the structure-activity relationship and systematic development of PBRP, establishing a theoretical foundation for the potential utilization of PBRP as functional natural drugs in alleviating aging diseases and its complications.