Atractylenolide I protects against lipopolysaccharide - induced disseminated intravascular coagulation by anti-inflammatory and anticoagulation effect

Objective: To investigate whether atractylenolide 1. (ATL-I) has protective effect on Iipopolysaccharidc (LPS)-induced disseminated intravascular coagulation (DIC) in vim and in vitro, and explore whether NF-kappa B signaling pathway is involved in ATL-I treatment. Methods: New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6 h at a rate of 600 mu g/kg (10 mL/h). Similarly, in the treatment groups. 1.0, 2.0, or 5.0 mg/kg ATLI. were given. Both survival rate and organ function were tested, including the level of alaninc aminotransferase (ALT), blood urine nitrogen (BUN). and TNF-,were examined by ELISA. Also haemostatic and fibrinolytic parameters in serum were measured. RAW 264.7 macrophage cells were administered with control, LPS, LPS + ATL- I and ATL- I alone, and TNF- alpha phosphorylation (P)-I kappa B alpha . phosphorylation (P)-NF- kappa B (P65) and NF-kappa B (P65) were determined by Western blot. Results: The administration of LPS resulted in 73.3% mortality rate, and the increase of serum TNF-alpha, BUN and ALT levels. When ATL-I treatment significantly increased the survival rate of LPS-induced DIC model, also improved the function of blood coagulation. And protein analysis indicated that ATL-lremarkahly protected liver and renal as decreasing TNF- a expression. In vitro, ATL-I obviously decreased LPS-induced TNF-alpha production and the expression of P-NF-kappa B (P65), with the decrease of P-I kappa Ba. Conclusions: ATL- has protective effect on LPS-induced DIC. which can elevate the survival rate, reduce organ damage, improve the function of blood coagulation and suppress TNF-alpha expression by inhibiting the activation of NF-kappa B signaling pathway.