Anti-inflammatory Activity of Baicalein in LPS-Stimulated RAW264.7 Macrophages via Estrogen Receptor and NF-κB-Dependent Pathways
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Baicalein has been used for many years as a popular antiviral and antibacterial in China. Recent investigations revealed that baicalein also has anti-inflammatory activities. Our results indicated that baicalein increases ERE-luciferase activity in an estrogen receptor (ER)-dependent manner when either ERα or ERβ were coexpressed in Hela cells. This study examined whether baicalein exerts an anti-inflammatory effect in RAW264.7 cells through an estrogen receptor-dependent pathway and through regulation of NF-ĸB activation. In lipopolysaccharide (LPS)-induced RAW264.7 cells, baicalein exerts anti-inflammatory effects by inhibiting iNOS, COX-2, and TNF-α mRNA expression; NO production; as well as inflammatory cytokine (IL-1β, PGE2, and TNF-α) production through an ER-dependent pathway. These effects are accompanied with the inhibition of the transcription factor NF-ĸB activation and IκBα phosphorylation. We therefore conclude that baicalein inhibits LPS-induced inflammatory cytokine production via regulation of the NF-ĸB pathway and estrogen-like activity, suggesting that it may be useful for preventing inflammation-related diseases.
KEY WORDSbaicalein estrogen-like activity phytoestrogen NF-kB RAW264.7 cells inflammation
We are grateful for the financial support from the National Key Basic Research Program of China (2012CB518400), the National Natural Science Foundation of China (81001659, 81273891), National Science Fund for Distinguished Young Scholars (81125024), the Program for Changjiang Scholars and Innovative Research Team in University (IRT1276), and Technology major projects (2012ZX09103201-046).
Conflict of interest
The authors declared that there is no conflict of interest.
- 2.Fan, G.W., X.M. Gao, H. Wang, Y. Zhu, J. Zhang, L.M. Hu, Y.F. Su, L.Y. Kang, and B.L. Zhang. 2009. The anti-inflammatory activities of Tanshinone IIA, an active component of TCM, are mediated by estrogen receptor activation and inhibition of iNOS. The Journal of Steroid Biochemistry and Molecular Biology 113: 275–280.PubMedCrossRefGoogle Scholar
- 16.Woo, K.J., J.H. Lim, S.I. Suh, Y.K. Kwon, S.W. Shin, S.C. Kim, Y.H. Choi, J.W. Park, and T.K. Kwon. 2006. Differential inhibitory effects of baicalein and baicalin on LPS-induced cyclooxygenase-2 expression through inhibition of C/EBPbeta DNA-binding activity. Immunobiology 211: 359–368.PubMedCrossRefGoogle Scholar
- 17.Singh, A.K., R. Singh, F. Naz, S.S. Chauhan, A. Dinda, A.A. Shukla, K. Gill, V. Kapoor, and S. Dey. 2012. Structure based design and synthesis of peptide inhibitor of human LOX-12: in vitro and in vivo analysis of a novel therapeutic agent for breast cancer. PloS One 7: e32521.PubMedCrossRefGoogle Scholar
- 25.Jobin, C., C.A. Bradham, M.P. Russo, B. Juma, A.S. Narula, D.A. Brenner, and R.B. Sartor. 1999. Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. The Journal of Immunology 163: 3474–3483.PubMedGoogle Scholar
- 26.Chi, D.S., T.C. Lin, K. Hall, T. Ha, C. Li, Z.D. Wu, T. Soike, and G. Krishnaswamy. 2012. Enhanced effects of cigarette smoke extract on inflammatory cytokine expression in IL-1beta-activated human mast cells were inhibited by baicalein via regulation of the NF-kappaB pathway. Clinical and Molecular Allergy : CMA 10: 3.PubMedCrossRefGoogle Scholar
- 28.Kasinski, A.L., Y. Du, S.L. Thomas, J. Zhao, S.Y. Sun, F.R. Khuri, C.Y. Wang, M. Shoji, A. Sun, J.P. Snyder, D. Liotta, and H. Fu. 2008. Inhibition of IkappaB kinase-nuclear factor-kappaB signaling pathway by 3,5-bis(2-flurobenzylidene)piperidin-4-one (EF24), a novel monoketone analog of curcumin. Molecular Pharmacology 74: 654–661.PubMedCrossRefGoogle Scholar
- 29.Kim, B.H., E. Roh, H.Y. Lee, I.J. Lee, B. Ahn, S.H. Jung, H. Lee, S.B. Han, and Y. Kim. 2008. Benzoxathiole derivative blocks lipopolysaccharide-induced nuclear factor-kappaB activation and nuclear factor-kappaB-regulated gene transcription through inactivating inhibitory kappaB kinase beta. Molecular Pharmacology 73: 1309–1318.PubMedCrossRefGoogle Scholar