The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Withaferin A Strongly Elicits IκB Kinase β Hyperphosphorylation Concomitant with Potent Inhibition of Its Kinase Activity
Open accessAbstract
The transcription factor NFkappaB plays a critical role in normal and pathophysiological immune responses. Therefore, NFkappaB and the signaling pathways that regulate its activation have become a major focus of drug development programs. Withania somnifera (WS) is a medicinal plant that is widely used in Palestine for the treatment of various inflammatory disorders. In this study we show that the leave extract of WS, as well as its major constituent withaferin A (WA), potently inhibits NFkappaB activation by preventing the tumor necrosis factor-induced activation of IkappaB kinase beta via a thioalkylation-sensitive redox mechanism, whereas other WS-derived steroidal lactones, such as withanolide A and 12-deoxywithastramonolide, are far less effective. To our knowledge, this is the first communication of IkappaB kinase beta inhibition by a plant-derived inhibitor, coinciding with MEK1/ERK-dependent Ser-181 hyperphosphorylation. This prevents IkappaB phosphorylation and degradation, which subsequently blocks NFkappaB translocation, NFkappaB/DNA binding, and gene transcription. Taken together, our results indicate that pure WA or WA-enriched WS extracts can be considered as a novel class of NFkappaB inhibitors, which hold promise as novel anti-inflammatory agents for treatment of various inflammatory disorders and/or cancer.
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Cites
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Cited by
Paul, S., Chakraborty, S., Anand, U., Dey, S., Nandy, S., Ghorai, M., Saha, S. C., Patil, M. T., Kandimalla, R., Proćków, J., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112175 · Cited by 306
Alam, N., Hossain, M., Mottalib, M. A., Sulaiman, S. A., Gan, S. H., & Khalil, M. I. (2012) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-12-175 · Cited by 159
García-Rivera, D., Delgado, R., Bougarne, N., Haegeman, G., & Vanden Berghe, W. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.02.011 · Cited by 142
Self-citationNatural Withanolides in the Treatment of Chronic Diseases
White, P. T., Subramanian, C., Motiwala, H. F., & Cohen, M. S. (2016) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-41334-1_14 · Cited by 139
Bonilla, D. A., Moreno, Y., Gho, C., Petro, J. L., Odriozola-Martínez, A., & Kreider, R. B. (2021) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk6010020 · Cited by 106
Metadata
- Authors
- Kaileh, M., Vanden Berghe, W., Heyerick, A., Horion, J., Piette, J., Libert, C., De Keukeleire, D., Essawi, T., & Haegeman, G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 282
- Issue
- 7
- Pages
- 4253-4264
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1993646281
- Cited by
- 301
- References
- 78
- FWCI
- 32.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Withaferin A Strongly Elicits IκB Kinase β Hyperphosphorylation Concomitant with Potent Inhibition of Its Kinase Activity. https://app.cochat.ai/papers/10.1074/jbc.m606728200
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- Kaileh, M., Vanden Berghe, W., Heyerick, A., Horion, J., Piette, J., Libert, C., De Keukeleire, D., Essawi, T., & Haegeman, G. (2007). Withaferin A Strongly Elicits IκB Kinase β Hyperphosphorylation Concomitant with Potent Inhibition of Its Kinase Activity. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m606728200
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