Differential Modulation of Colonic Inflammaging by Limonin Loaded in Pectin Emulsion Gels with Engineered Fine Structures

The emulsion gel (EG) system offers an effective strategy to improve limonin bioavailability, yet the differential intervention targets of limonin-loaded EGs constructed from pectins with distinct fine structures in colonic inflammaging remain unclear. In this study, three structurally distinct pectin-based EGs were engineered by modulating the degree of esterification and rhamnogalacturonan-I side-chain ratio. In d-galactose-induced aged mice, these EGs exhibited superior anti-inflammatory effects against colonic inflammaging compared to free limonin with distinct functional preferences. LMLRGI-EGL enhanced chemical and mechanical barriers and LMHRGI-EGL inhibited the pyroptosis pathway. In contrast, LMHRGI-EGL exhibited the broadest inhibitory effect on the pyroptosis signaling pathway, significantly ameliorating damage to the colonic immune barrier. Meanwhile, HMLRGI-EGL uniquely enriched the relative abundance of Erysipelotrichaceae and effectively suppressed the expression of the inflammatory cytokines. These findings demonstrate that structural variations in EGs enable differential regulation of colonic inflammaging through structure-dependent mechanisms.