Morroniside protects OLN-93 cells against H2O2-induced injury through the PI3K/Akt pathway-mediated antioxidative stress and antiapoptotic activities.

Neurodegenerative disorders, including spinal cord injury (SCI), result in oxidative stress-induced cell damage. Morroniside (MR), a major active ingredient of the Chinese herb Shan Zhu Yu, has been shown to ameliorate oxidative stress and inflammatory response. Our previous study also confirmed that morroniside protects SK-N-SH cell line (human neuroblastoma cells) against oxidative impairment. However, it remains unclear whether MR also plays a protective role for oligodendrocytes that are damaged following SCI. The present study investigated the protective effects of MR against hydrogen peroxide (H2O2)-induced cell death in OLN-93 cells. MR protected OLN-93 cells from H2O2-induced injury, attenuated H2O2-induced increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and blocked the reduction of mitochondrial membrane potential (MMP) induced by H2O2. MR enhanced the activity of the antioxidant enzyme superoxide dismutase (SOD) and suppressed H2O2-induced downregulation of the antiapoptotic protein Bcl-2 and activation of the proapoptotic protein caspase-3. Finally, we found that LY294002, a specific inhibitor of the PI3K/Akt pathway, inhibited the protective effect of MR against H2O2-induced OLN-93 cell injury in the MTT and TUNEL assays. LY294002 also inhibited the expression of SOD and Bcl-2, and increased the expression of iNOS and c-caspase-3 induced by MR treatment. MR exerts protective effects against H2O2-induced OLN-93 cell injury through the PI3K/Akt signaling pathway-mediated antioxidative stress and antiapoptotic activities. MR may provide a potential strategy for SCI treatment or other related neurodegeneration.

Resveratrol Downregulates STAT3 Expression and Astrocyte Activation in Primary Astrocyte Cultures of Rat.

Astrocytes respond to all forms of central nervous system (CNS) insults by a process referred to as reactive astrogliosis. Inhibition of astrocyte growth and activation is an important strategy for promoting injured CNS repair. STAT3 (signal transducer and activator of transcription 3) is reported to be a critical regulator of astrogliosis, and resveratrol (RES, a dietary polyphenol) is considered to be a natural inhibitor of STAT3 expression and phosphorylation. In this study, we investigated the effects of RES on STAT3 expression and phosphorylation, and then on the proliferation and activation of astrocytes, a critical process in reactive astrogliosis, in rat primary cultured astrocytes and an in vitro scratch-wound model. RES downregulated the expression levels of STAT3, P-STAT3 and GFAP (glial fibrillary acidic protein) in cultured astrocytes. The positive index of Ki67 was apparently reduced in cultured astrocytes after RES treatment. Meanwhile, cultured astrocyte proliferation and activation were attenuated by RES. Moreover, in the established in vitro scratch-wound model the increased expression levels of STAT3, P-STAT3 and GFAP induced by scratching injury were also clearly inhibited by RES. In addition, the inhibitory effect of RES on cell proliferation was similar to that of AG490 (a selective inhibitor of STAT3 phosphorylation) and abrogated by Colivelin (a STAT3 activator) stimuli. Taken together, our data suggest that RES is able to inhibit reactive astrocyte proliferation and activation mainly via deactivating STAT3 pathway. So RES may have a therapeutic benefit for the treatment of the injured CNS.