NOSH-aspirin (NBS-1120), a novel nitric oxide and hydrogen sulfide releasing hybrid, attenuates neuroinflammation induced by microglial and astrocytic activation: A new candidate for treatment of neurodegenerative disorders

Hydrogen sulfide (H2S) and nitric oxide (NO) have been described as gasotransmitters. Anti-inflammatory activity in the central and peripheral nervous systems may be one of their functions. Previously we demonstrated that several SH- donors including H2S-releasing aspirin (S-ASA) exhibited anti-inflammatory and neuroprotective activity in vitro against toxins released by activated microglia and astrocytes. Here we report that NOSH-ASA, an NO- and H2S-releasing hybrid of aspirin, has a significantly greater anti-inflammatory and neuroprotective effect than S-ASA or NO-ASA. When activated by LPS/IFN, human microglia and THP-1 cells release materials that are toxic to differentiated SH-SY5Y cells. These phenomena also occur with IFN-stimulated human astroglia and U373 cells. When the cells were treated with the S-ASA or NO-ASA, there was a significant enhancement of neuroprotection. However, NOSH-ASA had significantly more potent protection properties than NO-ASA or S-ASA. The effect was concentration-dependent, as well as incubation time-dependent. Such treatment not only reduced the release of the TNF and IL-6, but also attenuated activation of P38 MAPK and NFB proteins. All the compounds tested were not harmful when applied directly to SH-SY5Y cells. These data suggest that NOSH-ASA has significant anti-inflammatory properties and may be a new candidate for treating neurodegenerative disorders that have a prominent neuroinflammatory component such as Alzheimer disease and Parkinson disease. GLIA 2013;61:1724-1734