S-Allyl-l-cysteine (SAC) has been shown to reduce ischemic injury due to its antioxidant activity. However, the antioxidant property of SAC has been controversial. The present study investigated the neuroprotective mechanism of SAC in cerebral ischemic insults. SAC decreased the size of infarction after transient or global ischemic insults. While it did not alter the N-methyl-d-aspartate excitotoxicity, SAC significantly scavenged the endogenously or exogenously produced ONOO- and reduced ONOO- cytotoxicity. In contrast, SAC has much lower scavenging activity against H2O2, or NO. Further, SAC inhibited the activity of extracellular signal-regulated kinase (ERK) increased in cultured neurons exposed to oxygen-glucose deprivation or in rat brain tissue after transient middle cerebral artery occlusion. The neuroprotective effect of SAC was mimicked by the ERK inhibitor U0125. The present results indicate that SAC exert its neuroprotective effect by scavenging ONOO- and inhibiting the ERK signaling pathway activated during initial hypoxic/ischemic insults.
Bibliographical noteFunding Information:
This study was supported by a research project on Functional Food Development from the Office for Government Policy Coordination, a grant from the Agriculture R&D Promotion Center, under the Ministry of Agriculture and Forestry, a grant (M103KV010005 03K2201 00510) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, and in part a grant from the Korea Health 21 R&D Project (02-PJ1-PG6-AG01-0003) of the Ministry of Health & Welfare, the Republic of Korea.
- Peroxynitrite (ONOO)
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