Postharvest Aging and Harvest Stage Shape the Bioactive Profile, Hypolipidemic Activity, and Gut Microbiota-Modulating Effects of Citrus Peel Extracts in High-Fat-Diet-Fed Mice

Citri Reticulatae Pericarpium (CRP), a citrus peel product derived from Citrus reticulata, is rich in flavonoids and polysaccharides, yet the effects of harvest stage and postharvest aging on its composition and metabolic functionality remain unclear. In this study, green CRP (CRP-Q) and red CRP (CRP-H) aged for 1, 3, or 5 years were extracted with 70% ethanol and evaluated in high-fat-diet (HFD)-fed mice. CRP-1Q contained the highest levels of hesperidin, nobiletin, and tangeretin, reaching 58.09 ± 0.91, 14.78 ± 0.18, and 9.15 ± 0.08 mg/g, respectively. These three flavonoids generally declined with aging, whereas longer-aged extracts showed more consistent hypolipidemic effects. CRP extracts reduced serum triglyceride and total cholesterol levels, attenuated hepatic steatosis and epididymal fat accumulation, and regulated lipid metabolism-related enzymes and genes, including FAS, ACC, HSL, LPL, SREBP-1c, HMGCR, PPAR-α, and PPAR-γ. Gut microbiota composition also changed in several aged-CRP groups, with Akkermansia abundance increasing alongside improved metabolic indicators. These findings suggest that aging duration, more than harvest stage, shaped the functional properties of CRP extracts, while the stronger activity of aged CRP was not explained by the three quantified flavonoids alone.