title: Aqueous and Ethanol Extracts of Australian Cane Toad Skins Suppress Pro-Inflammatory Cytokine Secretion in U937 Cells via NF-κB Signaling Pathway.
abstract: Toad skin extracts, such as aqueous extracts (AE) of Chinese toad skins, have demonstrated therapeutic benefits for a range of diseases including pain, inflammation, swelling, heart failure, and various types of cancers. In this study, we investigated the anti-inflammatory potential of an AE (0.1-10 μg/mL) and a 60% ethanol extract (EE; 0.1-10 μg/mL) from Australian cane toad (Bufo marinus) skins and the known bioactive compound, bufotenine (BT; 0.1-10 nM). The assay employed a model of the human monocyte cell line U937 stimulated with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) for the release of tumor necrosis factor (TNF)-α and interleukin (IL)-6. We demonstrated that AE, EE, and BT significantly inhibited the release and expression of TNF-α and IL-6 in a dose-dependent manner when the cells were pre-treated at non-cytotoxic concentrations. Further investigation revealed that the inhibition of TNF-α and IL-6 release and expression was associated with the suppression of nuclear factor (NF)-kappa (κ)B activation. These results indicate that AE, EE, and BT are strong inflammation inhibitors, thus have the potential for further development as anti-inflammatory therapeutic agents from a natural source regarded as a feral pest in Australia. J. Cell. Biochem. 117: 2769-2780, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: School of Medical Science and Menzies Health Institute Queensland, Gold Coast Campus, Griffith University, Queensland, 4222, Australia.
authors.forename: Abu Hasanat Md
authors.initials: AH
authors.lastname: Zulfiker
authors.affiliation: School of Medical Science and Menzies Health Institute Queensland, Gold Coast Campus, Griffith University, Queensland, 4222, Australia.|Department of Biology, Deanship of Preparatory Year, University of Dammam, Dammam, Kingdom of Saudi Arabia.
authors.forename: Saeed M
authors.initials: SM
authors.lastname: Hashimi
authors.affiliation: School of Medical Science and Menzies Health Institute Queensland, Gold Coast Campus, Griffith University, Queensland, 4222, Australia.
authors.forename: Ji
authors.initials: J
authors.lastname: Qi
authors.affiliation: Institute for Glycomics and School of Medical Science, Gold Coast Campus, Griffith University, Queensland, 4222, Australia.
authors.forename: I Darren
authors.initials: ID
authors.lastname: Grice
authors.affiliation: School of Medical Science and Menzies Health Institute Queensland, Gold Coast Campus, Griffith University, Queensland, 4222, Australia. m.wei@griffith.edu.au.
authors.forename: Ming Q
authors.initials: MQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001001:Anura; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology*; D015153:Blotting, Western; D002018:Bufanolides / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D000431:Ethanol / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D002018:Bufanolides; D002316:Cardiotonic Agents; D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D013755:Tetradecanoylphorbol Acetate
keywords: 60% ETHANOL EXTRACT; AQUEOUS EXTRACT; AUSTRALIAN CANE TOAD SKIN; BUFOTENINE; U937 CELLS