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 (H 2 S) 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 H 2 S‐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 H 2 S‐releasing hybrid of aspirin, has a significantly greater anti‐inflammatory and neuroprotective effect than S‐ASA or NO‐ASA. When activated by LPS/IFNγ, human microglia and THP‐1 cells release materials that are toxic to differentiated SH‐SY5Y cells. These phenomena also occur with IFNγ‐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 TNFα and IL‐6, but also attenuated activation of P38 MAPK and NFκB 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