Ameliorative Effects of Newly Developed Citrus Hybrid "Mubong" Peel Extract on Experimental Colitis and Gut Microbiota Dysbiosis.

"Mubong," a newly developed citrus hybrid, is recognized for its unique flavor profile, yet its chemical composition and therapeutic potential remain unexplored. In the present work, we profiled the phytochemical content and antioxidant capacities of "Mubong" flesh and peel, then evaluated the anti-inflammatory effects of the "Mubong" Peel Extract (MPE) using in vitro (LPS-stimulated RAW 264.7 cells) and in vivo (DSS-induced colitis) models, coupled with microbiota analysis. In vitro anti-inflammatory activity was studied by measuring nitric oxide (NO) production and NF-κB signaling in RAW-Blue cells. In vivo, ICR mice were administered MPE (400 mg/kg) orally during DSS-induced colitis. Disease severity was evaluated through the Disease Activity Index (DAI), colon length, and histological analysis. To characterize microbial and metabolic shifts, we integrated 16S rRNA hypervariable region sequencing with targeted quantification of short-chain fatty acids (SCFAs). MPE was found to be rich in naringin (2730.66 ± 93.90 mg/100 g), neohesperidin (1493.85 ± 82.67 mg/100 g), and d-limonene (69.06%). In vitro, MPE (200-400 μg/mL) significantly inhibited NO production and suppressed NF-κB-dependent transcriptional activity. In mice, MPE treatment was associated with the attenuation of weight loss, reduction of DAI scores, and the mitigation of colon shortening. These clinical improvements were also coincided with a reduction in pro-inflammatory cytokines, specifically TNF-α (~80 to ~52 pg/mL) and IL-6 (~30 to ~3 pg/mL), and restoration of the SCFAs, propionic acid (~35% to ~80%) and butyric acid (~30% to ~50%). Microbiota analysis revealed that MPE treatment correlated with alterations in the gut landscape, specifically the enrichment of obligate anaerobes such as Lachnoclostridium and Acetatifactor. Furthermore, these microbial changes paralleled a recovery trend in short-chain fatty acids (butyrate and propionate) otherwise depleted by DSS. Our findings suggest that MPE exerts anti-inflammatory activity, likely through the modulation of NF-κB/AP-1-dependent transcriptional activity and preservation of gut microbial homeostasis. These preclinical findings suggest that "Mubong" warrants further investigation as a potential functional food candidate for the management of ulcerative colitis and related inflammatory disorders.