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Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis.
J Immunol. 1999 Dec 15; 163(12):6800-9.JI

Abstract

Silymarin is a polyphenolic flavonoid derived from milk thistle (Silybum marianum) that has anti-inflammatory, cytoprotective, and anticarcinogenic effects. How silymarin produces these effects is not understood, but it may involve suppression of NF-kappa B, a nuclear transcription factor, which regulates the expression of various genes involved in inflammation, cytoprotection, and carcinogenesis. In this report, we investigated the effect of silymarin on NF-kappa B activation induced by various inflammatory agents. Silymarin blocked TNF-induced activation of NF-kappa B in a dose- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of Iota kappa B alpha, an inhibitor of NF-kappa B. Silymarin blocked the translocation of p65 to the nucleus without affecting its ability to bind to the DNA. NF-kappa B-dependent reporter gene transcription was also suppressed by silymarin. Silymarin also blocked NF-kappa B activation induced by phorbol ester, LPS, okadaic acid, and ceramide, whereas H2O2-induced NF-kappa B activation was not significantly affected. The effects of silymarin on NF-kappa B activation were specific, as AP-1 activation was unaffected. Silymarin also inhibited the TNF-induced activation of mitogen-activated protein kinase kinase and c-Jun N-terminal kinase and abrogated TNF-induced cytotoxicity and caspase activation. Silymarin suppressed the TNF-induced production of reactive oxygen intermediates and lipid peroxidation. Overall, the inhibition of activation of NF-kappa B and the kinases may provide in part the molecular basis for the anticarcinogenic and anti-inflammatory effects of silymarin, and its effects on caspases may explain its role in cytoprotection.

Authors+Show Affiliations

Department of Molecular Oncology, Cytokine Research Laboratory, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10586080

Citation

Manna, S K., et al. "Silymarin Suppresses TNF-induced Activation of NF-kappa B, c-Jun N-terminal Kinase, and Apoptosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 12, 1999, pp. 6800-9.
Manna SK, Mukhopadhyay A, Van NT, et al. Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999;163(12):6800-9.
Manna, S. K., Mukhopadhyay, A., Van, N. T., & Aggarwal, B. B. (1999). Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. Journal of Immunology (Baltimore, Md. : 1950), 163(12), 6800-9.
Manna SK, et al. Silymarin Suppresses TNF-induced Activation of NF-kappa B, c-Jun N-terminal Kinase, and Apoptosis. J Immunol. 1999 Dec 15;163(12):6800-9. PubMed PMID: 10586080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. AU - Manna,S K, AU - Mukhopadhyay,A, AU - Van,N T, AU - Aggarwal,B B, PY - 1999/12/10/pubmed PY - 1999/12/10/medline PY - 1999/12/10/entrez SP - 6800 EP - 9 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 163 IS - 12 N2 - Silymarin is a polyphenolic flavonoid derived from milk thistle (Silybum marianum) that has anti-inflammatory, cytoprotective, and anticarcinogenic effects. How silymarin produces these effects is not understood, but it may involve suppression of NF-kappa B, a nuclear transcription factor, which regulates the expression of various genes involved in inflammation, cytoprotection, and carcinogenesis. In this report, we investigated the effect of silymarin on NF-kappa B activation induced by various inflammatory agents. Silymarin blocked TNF-induced activation of NF-kappa B in a dose- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of Iota kappa B alpha, an inhibitor of NF-kappa B. Silymarin blocked the translocation of p65 to the nucleus without affecting its ability to bind to the DNA. NF-kappa B-dependent reporter gene transcription was also suppressed by silymarin. Silymarin also blocked NF-kappa B activation induced by phorbol ester, LPS, okadaic acid, and ceramide, whereas H2O2-induced NF-kappa B activation was not significantly affected. The effects of silymarin on NF-kappa B activation were specific, as AP-1 activation was unaffected. Silymarin also inhibited the TNF-induced activation of mitogen-activated protein kinase kinase and c-Jun N-terminal kinase and abrogated TNF-induced cytotoxicity and caspase activation. Silymarin suppressed the TNF-induced production of reactive oxygen intermediates and lipid peroxidation. Overall, the inhibition of activation of NF-kappa B and the kinases may provide in part the molecular basis for the anticarcinogenic and anti-inflammatory effects of silymarin, and its effects on caspases may explain its role in cytoprotection. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10586080/Silymarin_suppresses_TNF_induced_activation_of_NF_kappa_B_c_Jun_N_terminal_kinase_and_apoptosis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10586080 DB - PRIME DP - Unbound Medicine ER -