Anti-Septic Potential of 7-α-Obacunyl Acetate Isolated from the Toona sinensis on Cecal Ligation/Puncture Mice via Suppression of JAK-STAT/NF-κB Signal Pathway

Abstract

Duo Li, Yibing Weng, Guan Wang, Genshen Zhen Department of Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of ChinaCorrespondence: Genshen ZhenDepartment of Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, No. 82, Xinhua South Road, Tongzhou District, Beijing, People’s Republic of ChinaTel [phone]-2121Email [email protected]: Sepsis is a life-threatening clinical syndrome and characterized by an inflammatory and innate immune response to infections. The current study was aimed to evaluate the anti-sepsis effect of 7-α-Obacunyl acetate (7-OBA), the abundant constituent isolated from Toona sinensis (Meliaceae), in cecal ligation and puncture (CLP)-induced mice and to investigate the related molecular mechanisms.Methods: The CLP operation was performed to establish the sepsis mice model, and the survival rate and temperature were measured after 7-OBA treatment (7.5, 15, and 30 mg/kg; i.p.). Inflammatory cytokines levels of TNF-α, IL-1β, IL-6, and IL-10 were detected by ELISA kits, and the kidney, liver, and heart function were measured using an automatic biochemistry analyzer. Effects of 7-OBA on NF-κB and JAK2-STAT3 signaling pathways were determined by Western blot analysis in a lipopolysaccharide (LPS) stimulated RAW264.7 cells model.Results: 7-OBA treatment significantly increased the survival rate (p< 0.05 and p< 0.01) and normalized temperature (p< 0.05 and p< 0.01) of sepsis mice. The levels of pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 in serum were obviously decreased, whereas the anti-inflammatory cytokines of IL-10 were increased. CLP-induced increases of the main markers of kidney, liver, and heart function in mice (p< 0.01) were also obviously reversed by 7-OBA. The anti-sepsis effect of 7-OBA might be associated with regulation of nuclear factor kappa-B (NF-κB) and Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signal pathways.Conclusion: Our investigation indicated that 7-OBA can be developed as an effective agent for treating/curing sepsis in the future.Keywords: 7-α-obacunyl acetate, Toona sinensis, sepsis, cecal ligation/puncture, JAK-STAT/NF-κB

Keywords

• 7-α-obacunyl acetate toona sinensis sepsis cecal ligation/puncture jak-stat/nf-κb