title: Baicalein exhibits anti-inflammatory effects via inhibition of NF-κB transactivation.
abstract: NF-κB is a crucial mediator of inflammatory and immune responses and a number of phytochemicals that can suppress this immune-regulatory transcription factor are known to have promising anti-inflammatory potential. However, we report that inducer of pro-inflammatory transcription factor NF-κB functions as an anti-inflammatory agent. Our findings reveal that a plant derived flavonoid baicalein could suppress mitogen induced T cell activation, proliferation and cytokine secretion. Treatment of CD4+ T cells with baicalein prior to transfer in to lymphopenic allogenic host significantly suppressed graft versus host disease. Interestingly, addition of baicalein to murine splenic lymphocytes induced DNA binding of NF-κB but did not suppress Concanavalin A induced NF-κB. Since baicalein did not inhibit NF-κB binding to DNA, we hypothesized that baicalein may be suppressing NF-κB trans-activation. Thioredoxin system is implicated in the regulation of NF-κB trans-activation potential and therefore inhibition of thioredoxin system may be responsible for suppression of NF-κB dependent genes. Baicalein not only inhibited TrxR activity in cell free system but also suppressed mitogen induced thioredoxin activity in the nuclear compartment of lymphocytes. Similar to baicalein, pharmacological inhibitors of thioredoxin system also could suppress mitogen induced T cell proliferation without inhibiting DNA binding of NF-κB. Further, activation of cellular thioredoxin system by the use of pharmacological activator or over-expression of thioredoxin could abrogate the anti-inflammatory action of baicalein. We propose a novel strategy using baicalein to limit NF-κB dependent inflammatory responses via inhibition of thioredoxin system.
authors.affiliation: Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Raghavendra S
authors.initials: RS
authors.lastname: Patwardhan
authors.affiliation: Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Maikho
authors.initials: M
authors.lastname: Thoh
authors.affiliation: Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Checker
authors.affiliation: Radiation Biology & Health Sciences Division, Modular Laboratories, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. Electronic address: sskumar@barc.gov.in.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Sandur
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D006086:Graft vs Host Disease / Q000473:pathology / Q000517:prevention & control; D008231:Lymphopenia / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D013879:Thioredoxins / Q000037:antagonists & inhibitors; D015533:Transcriptional Activation
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D044950:Flavanones; D008934:Mitogens; D016328:NF-kappa B; D003208:Concanavalin A; C006680:baicalein; D013879:Thioredoxins; D004247:DNA
keywords: 1-Chloro-2,4-dinitrobenzene (PubChem CID: 6); Baicalein; Baicalein (PubChem CID: 5281605); PX12 (PubChem CID: 219104); Selenite; Sodium selenite (PubChem CID: 24934); T cells; Thioredoxin reductase