Peroxynitrite scavenging mode of alaternin isolated from Cassia tora

Peroxynitrite (ONOO-), formed from the reaction of superoxide (.O2-) and nitric oxide (NO), is a potent oxidant that contributes to the oxidation of various cellular constituents, including lipids, amino acids, sulfhydryls and nucleotides. It can cause cellular injury, such as DNA fragmentation and apoptotic cell death. ONOO- toxicity is also reported to be involved in inflammatory and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and atherosclerosis. Moreover, the necessity for a strong ONOO- scavenger is important because of the lack of endogenous enzymes that protect against the damage caused by ONOO-. The aim of this study was to evaluate the ability of natural products to scavenge ONOO-. We tested various plant extracts for their ONOO- scavenging activity. Among them, extract from Cassia tora, which is well known as an oriental herb in traditional medicine, showed potent ONOO- scavenging activity. Further analysis identified the phenolic active components, alaternin and nor-rubrofusarin glucose, as potent ONOO- scavengers. Spectrophotometric analysis demonstrated that alaternin and nor-rubrofusarin glucose led to a decrease in the ONOO- -mediated nitration of tyrosine through electron donation. In bovine serum albumin, alaternin, but not nor-rubrofusarin glucose, showed significant inhibition of ONOO- -mediated nitration in a dose-dependent manner. We believe alaternin can be developed as an effective ONOO- scavenger for the prevention of ONOO- -associated diseases.