Preeclampsia (PE) is a major cause of fetal growth restriction and perinatal mortality, which involves oxidative stress and vasodilator signaling disorder. S-allyk-cysteine (SAC) is one of the most abundant compounds in garlic extracts, and possesses several biological activities. This research was designed to investigate the protective effects of SAC against H2O2-induced oxidative insults, as well as the effects on NO/cGMP signaling pathway in placenta. We used TEV-1 cells and placental explants to detect the effects of SAC. TEV-1 cells and human placental explants were separately exposed to SAC, H2O2, or a combination of H2O2 and SAC. Intracellular ROS was detected by flow cytometry; the NO level was detected by an NO metabolites (NOx) assay; the cGMP level was simultaneously measured by the method of radioimmunoassay; the expression of eNOS in 1EV-1 cells was measured by immunochemistry and Western blot. Our findings showed that H2O2 treatment increased ROS productions in 1EV-1 cells and significantly decreased cGMP and NO level either in 1EV-1 cells or explants compared to the control groups (p < 0.05). The expression of eNOS in TEV-1 cells also significantly decreased in H2O2 treated group compared to the control group (p < 0.05). Co-treatment of H2O2 and SAC significantly decreased ROS productions, and increased NO, cGMP and eNOS level compared to the H2O2 treated alone groups (p < 0.05), which were all reverted back to near control levels. Further more, SAC treatment increased NO and cGMP level of 1EV-1 cells and explants in a dose-dependent manner even at non-oxidative stress status (p < 0.05). However, when the 1EV-1 cells were cultured in the presence of NOS inhibitor (L-NAME) and NO donor (SNP), additional SAC treatment still significantly increased the NO level in comparison with SAC nontreated group (p < 0.05). In conclusion, these results demonstrate that ROS (H2O2-mediated) can induce insults to NO/cGMP pathway, while SAC could antagonize this insult. And SAC also possesses the ability to increase NO and cGMP level at non-oxidative stress status in 1EV-1 cells and placenta explants. SAC is therefore hypothesized to be a potential drug for PE treatment. (C) Elsevier Ltd. All rights reserved.