San‐Huang‐Xie‐Xin‐Tang Protects against Activated Microglia‐ and 6‐OHDA‐Induced Toxicity in Neuronal SH‐SY5Y Cells

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, PGE 2 , gp91 phox , iROS, TNF- α , IL-1 β , inhibition of I κ B α degradation and upregulation of HO-1. In addition, SHXT increased cell viability and down regulated nNOS, COX-2 and gp91 phox 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, gp91 phox and iROS, and inhibited I κ B α 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- κ 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.