Schisandrin B exhibits anti-inflammatory activity through modulation of the redox-sensitive transcription factors Nrf2 and NF-κB.

Abstract

Schisandrin B (SB), a dibenzocyclooctadiene derivative isolated from Schisandra chinensis and used commonly in traditional Chinese medicine for the treatment of hepatitis and myocardial disorders, has been recently shown to modulate cellular redox balance. Since we have shown that cellular redox plays an important role in the modulation of immune responses, the present studies were undertaken to study the effects of SB on activation and effector functions of lymphocytes. SB altered the redox status of lymphocytes by enhancing the basal reactive oxygen species levels and altering the GSH/GSSG ratio in lymphocytes. It also induced nuclear translocation of redox sensitive transcription factor Nrf2 and increased the transcription of its dependent genes. SB inhibited mitogen-induced proliferation and cytokine secretion by lymphocytes. SB also significantly inhibited mitogen-induced upregulation of T cell costimulatory molecules and activation markers. It was observed that SB inhibited mitogen-induced phosphorylation of c-Raf, MEK, ERK, JNK, and p38. It suppressed IκBα degradation and nuclear translocation of NF-κB in activated lymphocytes. Anti-inflammatory effects of SB were significantly abrogated by the inhibitors of Nrf2 and HO-1, suggesting the involvement of this pathway. Similar anti-inflammatory effects of SB on lymphocyte proliferation and cytokine secretion were also observed in vivo. To our knowledge, this is the first report showing that the anti-inflammatory effects of SB are mediated via modulation of Nrf2 and NF-κB in lymphocytes.

• Authors: Rahul Checker, Raghavendra S Patwardhan, Deepak Sharma, Jisha Menon, Maikho Thoh, Hari N Bhilwade, Tetsuya Konishi, Santosh K Sandur
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 53 Issue 7 Pg. 1421-30 (Oct 01 2012) ISSN: 1873-4596 [Electronic] United States
• PMID: 22917978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cyclooctanes
• Cytokines
• Lignans
• Membrane Proteins
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, mouse
• Polycyclic Compounds
• schizandrin B
• Concanavalin A
• Heme Oxygenase-1
• Hmox1 protein, mouse
• I-kappa B Kinase
• Mitogen-Activated Protein Kinase Kinases
• Proto-Oncogene Proteins p21(ras)

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Concanavalin A (pharmacology)
• Cyclooctanes (pharmacology)
• Cytokines (biosynthesis, immunology)
• Gene Expression Regulation
• Heme Oxygenase-1 (genetics, immunology)
• I-kappa B Kinase (genetics, immunology)
• Lignans (pharmacology)
• Lymphocyte Activation
• Lymphocytes (cytology, drug effects, immunology)
• Male
• Membrane Proteins (genetics, immunology)
• Mice
• Mitogen-Activated Protein Kinase Kinases (genetics, immunology)
• NF-E2-Related Factor 2 (genetics, immunology)
• NF-kappa B (genetics, immunology)
• Oxidation-Reduction
• Polycyclic Compounds (pharmacology)
• Proto-Oncogene Proteins p21(ras) (genetics, immunology)
• Signal Transduction
• Spleen (cytology, drug effects, immunology)