title: Trigonella seed extract ameliorates inflammation via regulation of the inflammasome adaptor protein, ASC.
abstract: Trigonella foenum-graecum (fenugreek) is an important medicinal plant, well known for its anti-inflammatory properties. However, the underlying cellular and molecular mechanisms of its action remain largely unknown. The apoptosis associated speck like protein containing a caspase recruitment domain (CARD) (ASC) is central to inflammatory and cell death pathways in innate and adaptive immunity. Here, we show that fenugreek seed extract provides cytoprotection to bacterial lipopolysaccharide (LPS) inflammed and nanosilica-treated fibroblasts via a reactive oxygen species independent pathway. All atom molecular dynamics simulations of ASC-ligand complex reveal that individual phytochemicals in fenugreek can bind to ASC via specific non-covalent interactions. These data show that a synergistic effect of fenugreek phytochemicals with the ASC protein alters its molecular properties resulting in altered cellular function. Such information is crucial to the development of targeted therapeutic interventions for inflammatory diseases.
authors.affiliation: Department of Biology, Indian Institute of Technology Jodhpur, Old Residency Road, Ratanada, Jodhpur, Rajasthan, India 342011.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Chennai, Tamilnadu, India 603203.
authors.forename: Samyuktha
authors.initials: S
authors.lastname: Suresh
authors.affiliation: Department of Chemistry, Indian Institute of Technology Jodhpur, Old Residency Road, Ratanada, Jodhpur, Rajasthan, India 342011.
authors.forename: Ananya
authors.initials: A
authors.lastname: Debnath
authors.affiliation: Department of Biology, Indian Institute of Technology Jodhpur, Old Residency Road, Ratanada, Jodhpur, Rajasthan, India 342011, sushmitajha@iitj.ac.in.
authors.forename: Sushmita
authors.initials: S
authors.lastname: Jha
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D016466:CHO Cells; D003412:Cricetulus; D004926:Escherichia coli; D005347:Fibroblasts / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008070:Lipopolysaccharides; D056004:Molecular Dynamics Simulation; D064209:Phytochemicals / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D029910:Trigonella / Q000737:chemistry*
chemical_list: D053468:CARD Signaling Adaptor Proteins; D008070:Lipopolysaccharides; D064209:Phytochemicals; D010936:Plant Extracts; D017382:Reactive Oxygen Species