Juglone Protects Against CLP-Induced Sepsis by Regulating Apoptosis, Pyroptosis, and Oxidative Stress Mechanisms

Background: Sepsis is a life-threatening systemic condition characterized by organ dysfunction resulting from a dysregulated host response to infection. This study aimed to investigate the protective role of juglone (5-hydroxy-1,4-naphthoquinone), a naturally occurring compound, on lung tissue in a cecal ligation and puncture (CLP)-induced sepsis model. Methods: Male Wistar-albino rats were used to establish the model, and juglone was administered intraperitoneally at doses of 1, 2, and 3 mg/kg. Lung and serum samples were collected for biochemical, molecular, and histological analyses through ELISA, RT-PCR, Western blot, and histopathological examinations. Results: In the sepsis group, the levels of proinflammatory cytokines (IL-1β, IL-6, IL-18) and pyroptosis-related markers (NLRP3, caspase-1, GSDMD) were significantly elevated, while juglone pretreatment markedly reduced these parameters in a dose-dependent manner. Moreover, juglone upregulated the Nrf2/HO-1 antioxidant pathway while downregulating Keap1 expression. RT-PCR analysis revealed that juglone suppressed the expression of pro-apoptotic genes (caspase-3, caspase-9, Bax) and enhanced anti-apoptotic Bcl-2 expression. Histopathological evaluation demonstrated that juglone alleviated inflammatory cell infiltration, septal thickening, and hemorrhage in lung tissue. Conclusions: These findings suggest that juglone is associated with protection against sepsis-induced lung injury and with changes in oxidative stress, inflammation, apoptosis, and pyroptosis pathways. Therefore, juglone may have protective potential against sepsis-induced pulmonary damage.