Bupleurum polysaccharides attenuates lipopolysaccharide-induced inflammation via modulating Toll-like receptor 4 signaling

• Published in: PloS one Vol. 8; no. 10; p. e78051
• Main Authors: Wu, Jian, Zhang, Yun-Yi, Guo, Li, Li, Hong, Chen, Dao-Feng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.10.2013; Public Library of Science (PLoS)
• Subjects: Adult respiratory distress syndrome; Animals; Bacteria; Bupleurum; Bupleurum - chemistry; CD14 antigen; Cell culture; Chromatography; Cytochemistry; Cytokines; Cytokines - biosynthesis; Cytokines - immunology; E coli; Enzyme-linked immunosorbent assay; Escherichia coli; Fluorescence; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Health aspects; Hemorrhage; Immune response; Immune system; Immunoglobulins; Immunomodulation; Inflammation; Inflammation - chemically induced; Inflammation - immunology; Inflammation - metabolism; Inflammation - pathology; Inflammatory diseases; Innate immunity; Interferon; Interleukin 12; Interleukin 6; Interleukin-1 Receptor-Associated Kinases - immunology; Interleukin-1 Receptor-Associated Kinases - metabolism; JNK protein; Kinases; Lipopolysaccharide Receptors - immunology; Lipopolysaccharide Receptors - metabolism; Lipopolysaccharides; Lipopolysaccharides - toxicity; Lungs; Macrophages; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - pathology; Male; MAP Kinase Kinase 4 - immunology; MAP Kinase Kinase 4 - metabolism; Mice; Mice, Inbred BALB C; Mitogens; NF-kappa B - immunology; NF-kappa B - metabolism; NF-κB protein; Phagocytes; Phagocytosis - drug effects; Phagocytosis - immunology; Pharmacology; Pharmacy; Polysaccharides; Polysaccharides - chemistry; Polysaccharides - pharmacology; Proteins; Rats; Rats, Wistar; Rodents; Saccharides; Signal transduction; Signal Transduction - drug effects; Signal Transduction - immunology; Signaling; TLR4 protein; TNF Receptor-Associated Factor 6 - immunology; TNF Receptor-Associated Factor 6 - metabolism; Toll-Like Receptor 4 - immunology; Toll-Like Receptor 4 - metabolism; Toll-like receptors; TRAF6 protein; Tumor necrosis factor-TNF; Tumor necrosis factor-α; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078051

Bupleurum polysaccharides (BPs), isolated from Bupleurum smithii var. parvifolium, possesses immunomodulatory activity, particularly on inflammation. Bacterial endotoxin lipopolysaccharide (LPS) triggers innate immune responses through Toll-like receptor 4 (TLR4) on host cell membrane. The present study was performed to evaluate whether the therapeutic efficacy of BPs on suppression of LPS's pathogenecity could be associated with the modulating of TLR4 signaling pathway. LPS stimulated expression and activation of factors in the TLR4 signaling system, including TLR4, CD14, IRAK4, TRAF6, NF-κB, and JNK, determined using immunocytochemical and/or Western blot assays. BPs significantly inhibited these effects of LPS. LPS increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-12p40, and IFN-β) and NO production, evaluated using ELISA and Griess reaction assays, respectively. BPs antagonized these effects of LPS. Interestingly, BPs alone augmented secretion of some pro-inflammatory cytokines of non-LPS stimulated macrophages and enhanced phagocytic activity towards fluorescent E.coli bioparticles. In a rat model of acute lung injury (ALI) with pulmonary hemorrhage and inflammation, BPs ameliorated lung injuries and suppressed TLR4 expression. The therapeutic properties of BPs in alleviating inflammatory diseases could be attributed to its inhibitory effect on LPS-mediated TLR4 signaling.