Diethyl Blechnic Exhibits Anti-Inflammatory and Antioxidative Activity via the TLR4/MyD88 Signaling Pathway in LPS-Stimulated RAW264.7 Cells

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 24; p. 4502
• Main Authors: He, Jia, Han, Shan, Li, Xin-Xing, Wang, Qin-Qin, Cui, Yushun, Chen, Yangling, Gao, Hongwei, Huang, Liting, Yang, Shilin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.12.2019; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Antioxidants; Antioxidants - chemistry; Antioxidants - pharmacology; Benzofurans - chemistry; Benzofurans - pharmacology; Chemokines; Cytokines; Cytokines - metabolism; Cytoplasm; Drug screening; Free radicals; Gene expression; Genes; Growth factors; Inflammation; Inflammation Mediators - metabolism; Kinases; Lipopolysaccharides; Lipopolysaccharides - immunology; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Mice; Molecular Structure; MyD88 protein; Myeloid Differentiation Factor 88 - metabolism; NF-kappa B - metabolism; Nuclear transport; Oxidative stress; Oxidative Stress - drug effects; Physiology; Proteins; RAW 264.7 Cells; Reactive Oxygen Species - metabolism; Signal transduction; Signal Transduction - drug effects; TAK1 protein; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Translocation; NF-κB; TLR4/MyD88; inflammation; diethyl blechnic; oxidative stress
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24244502

Inflammation is a common pathogenesis in many diseases. 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.