Sesaminol glucosides protect β-amyloid induced apoptotic cell death by regulating redox system in SK-N-SH cells.
ABSTRACT We have investigated the neuroprotective effect of sesaminol glucosides (SG) in SK-N-SH cells. SG prevented apoptotic cell death induced by Aβ₂₅₋₃₅. In parallel, SK-N-SH cells exposed to Aβ₂₅₋₃₅ underwent oxidative stress as shown by the elevated level of intracellular ROS, lipid peroxidation, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, which were effectively suppressed by SG treatment. Furthermore, SG reversed the activities of catalase and glutathione peroxidase, and restored intracellular GSH levels in Aβ₂₅₋₃₅ challenged SK-N-SH cells. In addition, SG inhibited not only Aβ₂₅₋₃₅-induced apoptotic features including cleavage of poly(ADP-ribose) polymerase, activation of caspase-3, and activation of caspase-9, but also elevated Bax/Bcl-2 ratio in SK-N-SH cells treated with Aβ₂₅₋₃₅. It was also observed that Aβ₂₅₋₃₅ stimulated the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular protein regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAP kinase. SG inhibited phosphorylation of the JNK, ERK and p38 MAP kinase. These results suggest that SG has a protective effect against Aβ₂₅₋₃₅-induced neuronal apoptosis, possibly through scavenging oxidative stress and regulating MAPKs signaling pathways.
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ABSTRACT: We previously demonstrated the preventive effect of sesamin, a lignan from sesame oil, on the development of several experimental models of hypertension. In the present study, we explored the mechanisms underlying the antihypertensive effect of sesamin using the deoxycorticosterone acetate (DOCA)-salt rat hypertensive model. After a 5-week treatment period, aortic superoxide (O2-) production was measured in the lucigenin chemiluminescence assay. Chemiluminescence signals significantly decreased in sesamin-containing diet-fed DOCA-salt hypertensive rats compared with those in the normal diet-fed DOCA-salt rats, although the signals in sham-operated control animals were not affected by the sesamin feeding. In addition, there was a positive correlation between systolic blood pressure and aortic O2- production. These findings suggest that sesamin feeding inhibits enhanced vascular O2- production in DOCA-salt hypertensive rats and that the antioxidative action of sesamin may contribute to its antihypertensive activity.Biological & Pharmaceutical Bulletin 10/2002; 25(9):1247-9. · 1.85 Impact Factor
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ABSTRACT: To investigate the possible role of oxidative RNA damage in the pathogenesis of Alzheimer's disease (AD), the concentrations of the oxidative stress marker 8-hydroxyguanosine (8-OHG) were measured in the cerebrospinal fluid (CSF) and the serum of patients with AD and control subjects. The concentration of 8-OHG in CSF in AD patients was approximately fivefold that in controls (P < 0.001). The concentration of 8-OHG in CSF decreased significantly with the duration of illness (r(s) = -0.48, P < 0.05) and the progression of cognitive dysfunctions (r(s) = 0.67, P < 0.01). However, the concentration of 8-OHG in CSF showed no correlation with that in serum in both the controls and AD patients. In addition, the concentration of 8-OHG in serum was not significantly altered in AD patients compared to that in controls, suggesting that the 8-OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue. These in vivo findings suggest a possible role of 8-OHG and increased oxidative RNA damage in the early stage of the development of AD.Journal of Neuroscience Research 11/2002; 70(3):447-50. · 2.97 Impact Factor
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ABSTRACT: Although the sesame lignans, sesaminol and sesamolinol, have been shown to possess antioxidative activity, less is known about the metabolism and antioxidative properties of sesamolin, a major constituent of sesame oil. To determine the ability of sesamolin to act as an antioxidant in vivo, we fed rats a diet containing 1% sesamolin for 2 wk and studied its metabolism and its effects on oxidative stress. About 75% of the ingested sesamolin was excreted unmetabolized in feces, but it was not detected in urine. Sesamolin and its metabolites, sesamol and sesamolinol, were excreted primarily as sulfates and glucuronides. The amount of sesamolin and its metabolites was lower in the plasma than in the liver or kidneys. When we compared rats fed a diet containing 1% sesamolin for 14 d with those fed a control diet, we found that liver weight was significantly greater in the former group. Lipid peroxidation activity, measured as 2-thiobarbituric acid reactive substances, was significantly lower in the kidneys and liver of the sesamolin-fed rats than in the controls. In addition, the amount of 8-hydroxy-2'-deoxyguanosine excreted in the urine was significantly lower in the sesamolin-fed rats. These results suggest that sesamolin and its metabolites may contribute to the antioxidative properties of sesame seeds and oil and support our hypothesis that sesame lignans reduce susceptibility to oxidative stress.Journal of Nutrition 07/1998; 128(6):1018-22. · 4.20 Impact Factor