Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION: FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

[Effect of qi benefiting stasis removing method on systemic inflammatory response and coagulation function in MODS patients].

OBJECTIVE: To observe the effect of qi benefiting stasis removing method (QBSRM) on systemic inflammatory response and coagulation function in multiple organ dysfunction syndrome (MODS) patients. METHODS: Totally 40 MODS patients who were admitted to Affiliated Hospital of Nanjing University of Traditional Chinese Medicine between May 2010 to December 2011 were randomly assigned to two groups, the experimental group (21 cases) and the control group (19 cases). Patients in the control group were treated with routine Western therapy, while those in the experimental group additionally took decoction for benefiting qi removing stasis. Inflammatory factors (including interleukin-1, interleukin-6, tumor necrosis factor-alpha) and coagulation parameters [including prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and D-dimer (DD)] were observed before treatment, and 3, 7, and 14 days after treatment in the two groups. RESULTS: At day 7 after treatment,levels of interleukin-1, interleukin-6, and PT were significantly lower in the experimental group than in the control group (P < 0.05). At day 14 after treatment, tumor necrosis factor-x and DD were significantly lower in the experimental group than in the control group (P < 0. 05). There was no statistical difference in APTT or FIB at day 3, 7 and 14 after treatment (P > 0.05). CONCLUSION: QBSRM could relieve systemic inflammatory response and improve coagulation functions.