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標題: Berberine induces heme oxygenase-1 up-regulation through phosphatidylinositol 3-kinase/AKT and NF-E2-related factor-2 signaling pathway in astrocytes
作者: Chen, J.H.
Huang, S.M.
Tan, T.W.
Lin, H.Y.
Chen, P.Y.
Yeh, W.L.
Chou, S.C.
Tsai, C.F.
Wei, I.H.
Lu, D.Y.
關鍵字: Berberine;Chinese herb;Heme oxygenase-1;Nrf2;Astrocytes;smooth-muscle-cells;suppresses neuroinflammatory responses;activated;protein-kinases;transcription factor;endothelial-cells;oxidative;stress;bv-2 microglia;nitric-oxide;lung injury;factor-i
Project: International Immunopharmacology
期刊/報告no:: International Immunopharmacology, Volume 12, Issue 1, Page(s) 94-100.
Our previous report has shown that berberine effectively inhibits LPS- and IFN-gamma-induced neuroinflammation in microglia cells. Recently, we also reported that HO-1 (Heme oxygenase-1) may be a therapeutic target to regulate neuroinflammation in microglia cells. The present study examined the ability of berberine, the major constituents of Chinese herb Rhizoma coptidis, to induce expression of HO-1, and analyzed its signaling mechanism in rat brain astrocytes. HO-1 is known as an antioxidant enzyme which helps to protect against cellular damage and maintains tissue homeostasis. Here, we found that berberine increased HO-1 mRNA and protein expression concentration- and time-dependently. In addition, berberine-induced HO-1 expression was attenuated by PI 3-kinase (phosphatidylinositol 3-kinase) inhibitors LY294002 and wortmannin, and an AKT inhibitor. Treatment of astrocytes with berberine also induced p85 (PI 3-kinase) and AKT phospholation, and increased AKT kinase activity. Berberine also increased NF-E2-related factor-2 (Nrf2) accumulation in the nucleus and increased Nrf2-DNA binding activity as determined by the EMSA (electrophoretic mobility shift assay). Moreover, berberine-induced increase of Nrf2-DNA binding activity was reduced by PI 3-kinase and AKT inhibitors. Berberine-increased HO-1-luciferase activity was also inhibited by co-transfection with dominant-negative (DN) mutants of p85 and AKT. Moreover, berberine-mediated increase of HO-1 transcriptional activity and protein expression were reduced by transfection with siRNA againt Nrf2. These findings suggest that berberine-increased HO-I expression is mediated by Nrf2 activation through the PI 3-kinase/AKT pathway in astrocytes. Thus, berberine may be useful as a therapeutic agent for the treatment of neuroinflammation-associated disorders. (C) 2011 Elsevier B.V. All rights reserved.
ISSN: 1567-5769
DOI: 10.1016/j.intimp.2011.10.019
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