Annona muricata Leaf Extract Rebalances Systemic Redox Status and Modulates Neuroimmune, Microbial, and Functional Responses in CLP-Induced Septic Rats

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.