Journal
PHYTOTHERAPY RESEARCH
Volume 31, Issue 1, Pages 152-163Publisher
WILEY
DOI: 10.1002/ptr.5746
Keywords
Withania somnifera; Withanolides; docking; cytokines; NF-kappa B; MAPK
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Funding
- Department of Biotechnology, New Delhi, India [BT/PR11845/GBD/27/168/2009]
- National Research Foundation of Korea (NRF) - Korea Government (MSIP) [2007-0054932]
- National R& D Program for Cancer Control Ministry of Health & Welfare, Republic of Korea [0720560]
- National Research Foundation of Korea [2007-0054932] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Innate inflammations are dominant causes of poor health and high mortality. The pathogen-associated molecular pattern and lipopolysaccharide (LPS) are sensed by immune cells through activation of toll-like receptor 4 leading to mitogen-activated protein kinases (MAPKs) and NF-kappa B activations. Controlled MAPK and Nf-kappa B inhibitors have been proposed as potential antiinflammatory drugs. Withania somnifera is an important medicinal herb with known antiinflammatory activity. In this study, the selected Withania somnifera extracts and withanolides were analysed on LPS-induced macrophages comparatively. Molecular docking analysis revealed withaferin A, withanone and withanolide A as effective withanolides against inflammatory target molecules. In experiments, withaferin A and withanone treatment had prominent suppressions on LPS-induced expression of pro-inflammatory cytokines in bone marrow-derived macrophages. Withaferin A regulated all the major four pathways (MAPKs and NF-kappa B) involved in innate inflammations. Similarly among the Withania extracts analysed, the in vitro propagated leaf and field grown root extracts containing high withaferin A content suppressed the inflammatory molecules through NF-kappa B and MAPK pathways. Withaferin A was found to be best in suppressing the activated inflammatory pathways among all the analysed withanolides. Therefore, withaferin A and extracts with high withaferin A content can be used as promising drug candidates against innate inflammations. Copyright (C) 2016 John Wiley & Sons, Ltd.
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