Annona muricata Leaf Extract Rebalances Systemic Redox Status and Modulates Neuroimmune, Microbial, and Functional...

Oxidative stress, immune dysregulation, and disturbed metabolic adaptation contribute to early sepsis pathophysiology. This exploratory study evaluated a commercial Annona muricata leaf extract in 40 male rats assigned to five groups (n = 8/group): healthy Control, laparotomy-only Sham, untreated cecal ligation and puncture (CLP), CLP plus a single 100 mg/kg extract dose, and CLP plus a single 200 mg/kg extract dose. Redox indices, circulating neuroendocrine and inflammatory biomarkers, bacterial translocation and peritoneal immune variables, 24 h functional measures, and multiorgan histopathology were assessed. All 40 animals reached the predefined 24 h endpoint. Relative to healthy Control and Sham animals, untreated CLP rats showed higher MDA, TOS, OSI, chemerin, asprosin, IL-1β, mesenteric lymph-node bacterial burden, peritoneal cfDNA, MPO activity, and anaerobic load, together with lower CAT, GPx, TAS, BDNF, circulating AMPK immunoreactivity, and phagocytic activity (all omnibus p < 0.001). The primary treatment comparison was with untreated CLP. Both extract doses shifted most continuous outcomes toward non-septic values, with the larger shift generally observed at 200 mg/kg; for example, MDA decreased from 6.92 ± 0.54 nmol/mL in untreated CLP rats to 4.15 ± 0.32 and 2.65 ± 0.21 nmol/mL at 100 and 200 mg/kg, respectively, while OSI decreased from 3.07 ± 0.28 to 1.21 ± 0.12 and 0.65 ± 0.06. Histological findings were heterogeneous and did not demonstrate uniform multiorgan protection. These data indicate short-term, dose-ordered associations between single-dose leaf-extract administration and biochemical, microbial, immune, and functional outcomes in this male-rat CLP model; they do not establish a molecular mechanism, direct antimicrobial activity, long-term survival benefit, safety, or clinical efficacy.