Schisandrin improves lipopolysaccharide‐induced acute lung injury by inhibiting the inflammatory response in vivo and in vitro

Abstract

Acute lung injury (ALI) is characterized by an excessive inflammatory response, closely related to sepsis occurrence and development. It has been reported that Schisandrin (Sch) exhibits anti-inflammatory activity. However, whether the beneficial effects of Sch exists during ALI remains to be studied. In this study, the impact of Sch was evaluated by studying lung tissue damage, measuring the concentrations of pro-inflammatory factors, and the expression of apoptotic proteins in the LPS-induced ALI mice model. Protein expression of inflammation-related signaling pathway within the lung tissue and A549 cells were also measured. In addition, the effect of Sch on A549 cell apoptosis and inflammatory markers was also detected. Animal experiments demonstrated that pre-feeding Sch alleviated the production of inflammation mediators, abnormal pathological injuries, and blocked the progression of apoptotic events in the lung tissue. The in vitro experiments showed that Sch pretreatment reduced LPS upregulated interleukin-1β (IL-1β), IL-18, and IL-6 levels, and improved LPS-induced abnormal apoptosis. Sch and the pathway inhibitor AG490 also inhibited the expression levels of p-JAK2 and p-STAT3 in A549 cells. Moreover, pretreatment with Sch significantly inhibited the activation of NLRP3 inflammasomes, reduced inducible nitric oxide synthase, and cyclooxygenase 2 proteins expression during ALI in vitro and in vivo. Overall, Sch effectively alleviated ALI and provided a new mechanism to support the protective effect of Sch for sepsis-induced ALI. Practical implicationsALI is characterized by inflammatory injury of the lungs, which is an important cause of high morbidity and mortality in severe patients. Sch is considered as a botanical active ingredient with various pharmacological activities, such as neuroprotective and vascular protective effects. However, the effect of Sch on ALI and its mechanism remains largely unknown. Research data indicate that Sch exerts an anti-inflammatory effect by reducing the production of inflammatory factors and abnormal apoptosis of cells, further alleviating lung damage. The protective effect of Sch was associated with inhibition of the activation of NLRP3 and the JAK2/STAT3 inflammatory pathways. The study, therefore, confirmed that Sch has a potential as an effective drug to prevent ALI diseases.

Fortunellin ameliorates LPS‐induced acute lung injury, inflammation, and collagen deposition by restraining the TLR4/NF‐κB/NLRP3 pathway

“…The excessive inflammatory response is a primary feature of ALI 25 . In LPS‐stimulated ALI, TLR4 identifies LPS and subsequently facilitates the NF‐κB activation 21 .…”

“…The excessive inflammatory response is a primary feature of ALI. 25 In LPS‐stimulated ALI, TLR4 identifies LPS and subsequently facilitates the NF‐κB activation. 21 NF‐κB activation triggers the secretions of inflammatory cytokines, such as TNF‐α, IL‐6, and IL‐1β.…”

Schisandrin protects against ulcerative colitis by inhibiting the SGK1/NLRP3 signaling pathway and reshaping gut microbiota in mice

“…Moreover, SCH is known to significantly inhibit the activation of the NLRP3 inflammasome during acute lung injury, reducing apoptosis and also declined the levels of IL-1β, IL-18, and IL-6 [ 14 ]. However, it is unclear whether SCH possesses an inhibitory effect on NLRP3 inflammasome in the case of UC [ 9 ].…”