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Background: The primary pathophysiological process of sepsis is to stimulate a massive release of inflammatory mediators to trigger systemic inflammatory response syndrome (SIRS), the major cause of multi-organ dysfunction and death. Like other helminths, Echinococcus granulosus induces host immunomodulation. We sought to determine whether E. granulosus cyst fluid (EgCF) displays a therapeutic effect on sepsis-induced inflammation and tissue damage in a mouse model., Methods: The anti-inflammatory effects of EgCF were determined by in vitro culture with bone marrow-derived macrophages (BMDMs) and in vivo treatment of BALB/C mice with cecal ligation and puncture (CLP)-induced sepsis. The macrophage phenotypes were determined by flow cytometry, and the levels of cytokines in cell supernatants or in sera of mice were measured (ELISA). The therapeutic effect of EgCF on sepsis was evaluated by observing the survival rates of mice for 72 h after CLP, and the pathological injury to the liver, kidney, and lung was measured under a microscope. The expression of TLR-2/MyD88 in tissues was measured by western blot to determine whether TLR-2/MyD88 is involved in the sepsis-induced inflammatory signaling pathway., Results: In vitro culture with BMDMs showed that EgCF promoted macrophage polarization to M2 type and inhibited lipopolysaccharide (LPS)-induced M1 macrophages. EgCF treatment provided significant therapeutic effects on CLP-induced sepsis in mice, with increased survival rates and alleviation of tissue injury. The EgCF conferred therapeutic efficacy was associated with upregulated anti-inflammatory cytokines (IL-10 and TGF-β) and reduced pro-inflammatory cytokines (TNF-α and INF-γ). Treatment with EgCF induced Arg-1-expressed M2, and inhibited iNOS-expressed M1 macrophages. The expression of TLR-2 and MyD88 in EgCF-treated mice was reduced., Conclusions: The results demonstrated that EgCF confers a therapeutic effect on sepsis by inhibiting the production of pro-inflammatory cytokines and inducing regulatory cytokines. The anti-inflammatory effect of EgCF is carried out possibly through inducing macrophage polarization from pro-inflammatory M1 to regulatory M2 phenotype to reduce excessive inflammation of sepsis and subsequent multi-organ damage. The role of EgCF in regulating macrophage polarization may be achieved by inhibiting the TLR2/MyD88 signaling pathway., (© 2023. The Author(s).)

Background: Here, by using the lipopolysaccharide (LPS)-induced mice sepsis model, we treated septic wild-type (WT) mice or MEK1 DD mice with rigosertib to evaluate its prospective effects on sepsis., Methods: We also generated macrophages derived from bone marrow from WT or MEK1 DD mice. These macrophages were pretreated with rigosertib and then induced with LPS or poly I:C., Results: Rigosertib suppressed LPS or poly I:C-induced expression of inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6], and IL-23) in WT bone marrow-derived macrophages while failed to affect the upregulation of TNF-α and IL-6 in LPS-treated bone marrow-derived macrophages from MEK1 DD mice. Rigosertib promoted survival rate, ameliorated lung injury, and reduced inflammatory cytokine levels in serum of WT septic mice., Conclusion: In contrast, the effects of rigosertib on sepsis were abrogated in septic MEK1 DD mice, which had inducible constitutive activation of MEK1 signaling. Rigosertib alleviated LPS-induced sepsis inhibits MEK1/ERK signaling pathway., (© 2021 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.)

Sepsis is a deadly complication raised by bacterial pathogens-induced dysregulated innate inflammatory response. Thus, anti-inflammatory is a potential therapeutic treatment for septic patients. Numerous evidence exhibited that berberine possesses potent anti-inflammatory, anti-apoptotic and anti-oxidative activities. However, the effect of berberine on sepsis is not fully understood. The anti-inflammatory effect of berberine was evaluated using lipopolysaccharide (LPS)-induced macrophages differentiation model in vitro and using LPS/D-galactosamine-challenged septic mice model in vivo. The secreted protein levels were determined by ELISA assay. The multiple targets mRNA and protein levels were measured by quantitative RT-PCR and western blot assay, respectively. Our study demonstrated that administration of berberine significantly attenuated lung tissue injury, and potently increased the survival rate of septic mice by modulating excessive inflammatory response with negligible side-effects. We further found that berberine inhibited the expression of tumor necrosis factor (TNF)-α, interleukin-(IL)-1β and IL-6 via suppressing nuclear factor kappa B subunit 1 (NF-κB) signaling activation. Our study strongly supported the concept that berberine may serve as a single drug or a promising adjuvant that can be used in conjunction with other medications for the treatment of septic patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.)