[Frontiers In Bioscience, Elite, 9, 246-257, March 1, 2017]

Trigonella seed extract ameliorates inflammation via regulation of the inflammasome adaptor protein, ASC

Nidhi Sharma1, Samyuktha Suresh2, Ananya Debnath3, Sushmita Jha1

1Department of Biology, Indian Institute of Technology Jodhpur, Old Residency Road, Ratanada, Jodhpur, Rajasthan, India 342011, 2Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur, Chennai, Tamilnadu, India 603203, 3Department of Chemistry, Indian Institute of Technology Jodhpur, Old Residency Road, Ratanada, Jodhpur, Rajasthan, India 342011

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
4. Results
5. Discussion
6. Acknowledgements
7. References

1. 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.

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Abbreviations: ASC: Apoptosis-associated speck-like protein containing Caspase recruitment domain, CARD: Caspase recruitment domain, LPS: bacterial lipopolysaccharide, RMSF: Root mean square fluctuations, RMSD: Root mean square deviations

Key Words: ASC, NLR, Fenugreek, Phytochemicals, Inflammation, Antioxidants

Send correspondence to: Sushmita Jha, Department of Biology, Indian Institute of Technology Jodhpur, Old Residency Road, Ratanada, Jodhpur, Rajasthan, India 342011, Tel: 91-291- 244-9083, Fax: 91-291-251-6823, e-Mail: sushmitajha@iitj.ac.in