Abstract
Inflammation is a common pathogenesis in many diseases. Salvia miltiorrhiza Bunge (Danshen), a traditional Chinese medicine, has been considered to have good anti-inflammatory effects. In the present study, we investigated the anti-inflammatory effect of diethyl blechnic (DB), a novel compound isolated from Danshen, and its possible mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. The results showed that DB can inhibit the LPS-induced pro-inflammatory cytokines release of prostaglandin E2 (PGE2) and mRNA expression of TNF-α, IL-6, and IL-1β. In addition, the results of the flow cytometry assay and the fluorometric intracellular ROS kit assay indicated that DB reduced the generation of ROS in LPS-stimualted RAW264.7 cells. DB reversed the LPS-induced loss of the mitochondrial membrane potential (MMP). Furthermore, DB suppressed the LPS-stimulated increased expression of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88) and phosphorylation of TAK1, PI3K, and AKT. DB promoted NF-E2-related factor 2 (Nrf2) into the nucleus, increased the expression of heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase [quinone] 1 (NQO1) and reduced the expression of Keap1. In summary, DB may inhibit LPS-induced inflammation, which mainly occurs through TLR4/MyD88 and oxidative stress signaling pathways in RAW264.7 cells.
Highlights
Inflammation is the body’s physiological defense response to different stimuli [1,2]
Diethylblechnic blechnic(Figure (Figure1A), 1A),aanovel novelnatural naturalproduct productisolated isolatedfrom fromSalvia
In showed no significant cytotoxicity in RAW264.7 cells compared with normal control (Figure 1B)
Summary
Inflammation is the body’s physiological defense response to different stimuli [1,2]. Moderate inflammation can enhance the body’s autoimmune response, but excessive inflammation activates immune cells, which can damage both healthy and damaged tissues. Stimulated cells proliferate, differentiate, and secrete inflammatory factors, chemokines, and other factors to promote the occurrence and development of tissue inflammation [3]. Macrophages have an important role in an inflammatory response and are the central cells that initiate the production of inflammatory mediators [4]. LPS is an important inflammation trigger, which induces cytokines to participate in inflammation [5]. The LPS-induced RAW264.7 model has been widely used in the study of inflammation [6]
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