Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 53, Issue 7, Pages 1421-1430Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2012.08.006
Keywords
Reactive oxygen species; Heme oxygenase-1; Glutathione; Lymphocytes; Cytokines; Free radicals
Funding
- Department of Atomic Energy, Government of India
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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-incluced 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 I kappa B alpha degradation and nuclear translocation of NF-kappa B 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-kappa B in lymphocytes. (C) 2012 Elsevier Inc. All rights reserved.
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