Pomegranate Peel Extract and Punicalagin Are Associated with Attenuated Intestinal Barrier Dysfunction, Oxidative Stress, and Multi-Organ Injury in a Rat CLP Model

Background/Objectives: Cecal ligation and puncture (CLP)-induced sepsis is accompanied by intestinal tight-junction disruption, circulating markers of barrier dysfunction, oxidative stress, bacterial dissemination, and multi-organ injury. This study evaluated the protective effects of chemically characterized pomegranate peel extract (PPE) and punicalagin (PUN) in a rat CLP model. Methods: Forty-eight female Wistar rats were randomized into six groups (n = 8): Sham, CLP, CLP + PPE 150 mg/kg, CLP + PPE 300 mg/kg, CLP + PUN 50 mg/kg, and non-septic PPE 300 mg/kg. Treatments were administered orally 1 h after surgery. Animals were monitored for 48 h and sampled at a predefined humane endpoint or at 48 h. Results: CLP reduced ileal ZO-1 and occludin abundance and increased serum diamine oxidase, D-lactate, and plasma endotoxin (all omnibus p < 0.001). Relative to untreated CLP, PPE 300 mg/kg increased ZO-1 and occludin by 219% and 236%, respectively, and reduced circulating markers consistent with intestinal barrier dysfunction, oxidative stress, lactate, and multi-organ injury. PPE 300 mg/kg and PUN 50 mg/kg were also associated with higher hepatic SIRT1/PGC-1α expression, lower recoverable aerobic bacterial burden, less histological injury, and higher observed 48 h survival (7/8 and 8/8 vs. 2/8 in CLP). Conclusions: PPE and PUN produced coordinated protective changes in this experimental CLP model. These biomarker-based and survival findings support further preclinical investigation of standardized pomegranate-derived preparations as potential adjunctive interventions; they do not establish direct intestinal permeability, mitochondrial restoration, clinical therapeutic efficacy, or a punicalagin-mediated mechanism.