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eCAM Advance Access published online on April 1, 2009
eCAM, doi:10.1093/ecam/nep025
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© 2009 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

San-Huang-Xie-Xin-Tang Protects Against Activated Microglia- and 6-OHDA-induced Toxicity in Neuronal SH-SY5Y Cells

Yu-Tzu Shih1, Ing-Jun Chen2, Yang-Chang Wu1 and Yi-Ching Lo2

1Graduate Institute of Natural Products and, and 2Department of Pharmacology, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC

San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix and Rhei rhizoma, is a traditional Chinese herbal medicine used to treat gastritis, gastric bleeding and peptic ulcers. This study investigated the neuroprotective effects of SHXT on microglia-mediated neurotoxicity using co-cultured lipopolysaccharide (LPS)-activated microglia-like BV-2 cells with neuroblastoma SH-SY5Y cells. Effects of SHXT on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity were also examined in SH-SY5Y cells. Results indicated SHXT inhibited LPS-induced inflammation of BV-2 cells by downregulation of iNOS, NO, COX-2, PGE2, gp91phox, iROS, TNF-{alpha}, IL-1β, inhibition of I{kappa}B{alpha} degradation and upregulation of HO-1. In addition, SHXT increased cell viability and down regulated nNOS, COX-2 and gp91phox of SH-SY5Y cells co-cultured with LPS activated BV-2 cells. SHXT treatment increased cell viability and mitochondria membrane potential (MMP), decreased expression of nNOS, COX-2, gp91phox and iROS, and inhibited I{kappa}B{alpha} degradation in 6-OHDA-treated SH-SY5Y cells. SHXT also attenuated LPS activated BV-2 cells- and 6-OHDA-induced cell death in differentiated SH-SY5Y cells with db-cAMP. Furthermore, SHXT-inhibited nuclear translocation of p65 subunit of NF-{kappa}B in LPS treated BV-2 cells and 6-OHDA treated SH-SY5Y cells. In conclusion, SHXT showed protection from activated microglia- and 6-OHDA-induced neurotoxicity by attenuating inflammation and oxidative stress.

Keywords: lipopolysaccharide – microglial – neuroprotection – oxidative stress – San-Huang-Xie-Xin-Tang – 6-hydroxydopamine

For reprints and all correspondence: Dr Yi-Ching Lo, Department of Pharmacology, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan, ROC. Tel/Fax: +886-7-3234686, E-mail: yichlo{at}kmu.edu.tw

Received July 21, 2008; accepted March 3, 2009


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