Antioxidative and Anti-Inflammatory Neuroprotective Effects of Astaxanthin and Canthaxanthin in Nerve Growth Factor Differentiated PC12 Cells

ABSTRACT: Nerve growth factor differentiated PC12 cells were used to examine the antioxidative and anti‐inflammatory effects of astaxanthin (AX) and canthaxanthin (CX). PC12 cells were pretreated with AX or CX at 10 or 20 μM, and followed by exposure of hydrogen peroxide (H₂O₂) or 1‐methyl‐4‐phenylpyridinium ion (MPP⁺) to induce cell injury. H₂O₂ or MPP⁺ treatment significantly decreased cell viability, increased lactate dehydrogenase (LDH) release, enhanced DNA fragmentation, and lowered mitochondrial membrane potential (MMP) (P < 0.05). The pretreatments from AX or CX concentration‐dependently alleviated H₂O₂ or MPP⁺‐induced cell death, LDH release, DNA fragmentation, and MMP reduction (P < 0.05). Either H₂O₂ or MPP⁺ treatment significantly increased malonyldialdehyde (MDA) and reactive oxygen species (ROS) formations, decreased glutathione content, and lowered glutathione peroxidase (GPX) and catalase activities (P < 0.05). The pretreatments from AX or CX significantly retained GPX and catalase activities, and decreased MDA and ROS formations (P < 0.05). H₂O₂ or MPP⁺ treatment significantly decreased Na⁺‐K⁺‐ATPase activity, elevated caspase‐3 activity and levels of interleukin (IL)‐1, IL‐6, and tumor necrosis factor (TNF)‐α (P < 0.05); and the pretreatments from these agents significantly restored Na⁺‐K⁺‐ATPase activity, suppressed caspase‐3 activity and release of IL‐1, IL‐6, and TNF‐α (P < 0.05). Based on the observed antioxidative and anti‐inflammatory protection from AX and CX, these 2 compounds were potent agents against neurodegenerative disorder.     

Analysis of glycative products in sauces and sauce-treated foods

Content of Maillard reaction products (MRPs) such as pentosidine, carboxymethyllysine and furosine in soybean sauce, sour-sweet sauce, tomato sauce, barbecue sauce, and sauce-treated chicken, pork, beef, salmon and cod was analysed. In test sauces, MRP content was in the range of 10–692 μg/100 mL sample. MRP content in raw, boiled, fried and baked foods was in the range of 10–76 μg/100 g sample. Boiling, frying and baking caused significantly higher MRP levels in test foods (P < 0.05). MRP levels in soybean sauce, sour-sweet sauce and barbecue sauce-treated foods were in the range of 1094–2424, 1494–3146 and 1400–2926 μg/100 g sample. The interactions of sauce, heating and frying oil markedly enhanced the formation of MRPs in sauce-treated foods. Because MRPs are glycative products; thus, patients with glycation associated diseases may consider limiting the dietary use of these sauces.     

Effect of five cysteine-containing compounds on three lipogenic enzymes in Balb/cA mice consuming a high saturated fat diet

The in vivo effects of N-acetyl cysteine (NAC), S-allyl cysteine, S-ethy cysteine (SEC), S-methyl cysteine (SMC), and S-propyl cysteine (SPC) against hyperlipidemia development and oxidation stress in Balb/cA mice consuming a high saturated fat diet were examined. The influence of these agents on plasma levels of glucose, insulin, uric acid, TG, cholesterol, and the activity of three lipogenic enzymes—glucose-6-phosphate dehydrogenase, malic enzyme, and FA synthase—was determined. All mice consumed the coconut oil-basd, high saturated fat diet, water, and cysteine or one of the five cysteine-containing compounds for 4 wk. The diet with 18% saturated fat significantly elevated the activity of three lipogenic enzymes and significantly increased TG and cholesterol biosynthesis in plasma and liver (P<0.05). When compared with the water and cysteine groups, the treatments from five cysteine-containing agents significantly reduced high saturated fat diet-increased malic enzyme and FA synthase activities, and significantly lowered TG levels in plasma and liver (P<0.05); however, only NAC, SAC, and SMC treatments significantly reduced cholesterol levels in plasma and liver (P<0.05). The five cysteine-containing agents significantly restored high saturated fat diet-decreased glutathione peroxidase (GPX) activity in liver (P<0.05); however, only SMC and SPC significantly restored GPX activity in heart and kidney (P<0.05). These agents also significantly improved high saturated fat diet-related hyperglycemia, hyperuricemia, and oxidation stress (P<0.05). These data support the hypothesis that these compounds are potential multiply-protective agents for hyperlipidemia prevention or therapy.     

Protective action on human LDL against oxidation and glycation by four organosulfur compounds derived from garlic

Human LDL were used to study the protective action of four organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic against oxidation and glycation. The four organosulfur compounds significantly inhibited superoxide production by xanthine-xanthine oxidase (P<0.05) and showed marked copper-chelating capability. DAS and DADS exhibited greater antioxidant activities against copper- and amphotericin B-induced LDL oxidation (P<0.05) than SEC and NAC. However, SEC and NAC were more effective in sparing LDL α-tocopherol (P<0.05). When oxidation was minimized, SEC was the most powerful agent against LDL glycation (P<0.05); however, DADS was superior to other agents in suppressing both oxidation and glycation when LDL oxidation occurred simultaneously with glycation. These results suggest that the four organosulfur compounds derived from garlic are potent agents for protecting LDL against oxidation and glycation, and that they may benefit patients with diabetes mellitus or cardiovascular diseases by preventing complications.     

Protective and alleviative effects from 4 cysteine-containing compounds on ethanol-induced acute liver injury through suppression of oxidation and inflammation

ABSTRACT:  In vivo protective and alleviative effects of s-allyl cysteine (SAC), s-ethyl cysteine (SEC), s-methyl cysteine (SMC), and s-propyl cysteine (SPC) against alcohol-induced hepatotoxicity in Balb/cA mice were studied. In the preventive study, SAC, SEC, SMC, or SPC, each agent at 1 g/L, was added into the drinking water for 3 wk, and the mice were then treated with ethanol to induce acute liver injury. In the alleviative study, mice were first treated by ethanol followed by the 4 agent treatments for 3 wk. The preintake of these agents significantly attenuated subsequent alcohol-induced lipid oxidation, glutathione (GSH) depletion, and activity reduction of catalase and glutathione peroxidase ( P < 0.05); also attenuated were the alcohol-induced elevation of c-reactive protein (CRP), interleukin-6 (IL-6), IL-10 and tumor necrosis factor (TNF)-alpha ( P < 0.05). The preintake of these agents also significantly retarded alcohol-induced cytochrome P450 2E1 (CYP2E1) activity increase ( P < 0.05). In the alleviative study, posttreatments from the 4 agents restored liver GSH content ( P < 0.05); however, only SEC and SPC posttreatments significantly reduced lipid oxidation and alleviated the alcohol-induced elevation of CRP, IL-6, IL-10, and TNF-alpha ( P < 0.05). SEC and SPC posttreatments also significantly diminished alcohol induced CYP2E1 activity ( P < 0.05). These results support that SEC and SPC could provide both preventive and alleviative effects against alcohol-induced hepatotoxicity through suppression of oxidation and inflammation.     

Anti-Campylobacter, anti-aerobic, and anti-oxidative effects of roselle calyx extract and protocatechuic acid in ground beef

The inhibitory effect of roselle calyx extract and protocatechuic acid against susceptible and antibiotic-resistant Campylobacter jejuni, C. coli and C. fetus in agar plate and ground beef was examined. The minimal inhibitory concentrations of roselle calyx extract and protocatechuic acid against susceptible and antibiotic-resistant Campylobacter species were in the range of 96-152 and 20-44 mug/ml, respectively. Temperature treatments from 25 to 100 degrees C did not affect the anti-Campylobacter activity of protocatechuic acid. In ground beef stored at 15 degrees C for 6 days, roselle calyx extract and protocatechuic acid inhibited the survival and growth of aerobes, and susceptible and antibiotic-resistant Campylobacter species, in which protocatechuic acid exhibited dose-dependent effect. Both roselle calyx extract and protocatechuic acid decreased lipid oxidation levels in ground beef, in which protocatechuic acid also exhibited dose-dependent effect. The addition of roselle calyx extract or protocatechuic acid did not affect cooking loss, pH value, sensory attributes and content of fat, protein and moisture of beef samples during storage at 4 degrees C for 15 days. These data support that roselle calyx extract and protocatechuic acid may be used for muscle foods to prevent contamination from Campylobacter and aerobes, as well as delay lipid oxidation.     

Antioxidative characteristics of aqueous and ethanol extracts of glossy privet fruit

Non-enzymatic antioxidant activities of aqueous extract, 50% ethanol extract and 75% ethanol extract of glossy privet fruit were examined. Aqueous and ethanol extracts contained various concentrations of phenolic acids, flavonoids, oleanolic acid and ursolic acid. Each extract scavenged superoxide anion, hydroxyl radical and nitric oxide (P < 0.05) in a concentration-dependent manner and the effect of 75% ethanol extract was significantly greater than other extracts (P < 0.05). Each extract showed a concentration-dependent effect on chelating effect, xanthine oxidase inhibition activity and reducing power (P < 0.05). Compared with controls, each extract significantly decreased malondialdehyde formation in low density lipoprotein (LDL) and 8-epi-PGF_2α formation in plasma (P < 0.05). Aqueous extract exerted a greater effect than ethanol extract on increasing catalase and glutathione peroxidase activities in plasma (P < 0.05). These data suggest that using glossy privet fruit extracts may enhance lipid stability in food systems, and provide antioxidative protection for LDL and plasma.     

Antiglycative and anti-VEGF effects of s-ethyl cysteine and s-propyl cysteine in kidney of diabetic mice

Antiglycative and antivascular endothelial growth factor (VEGF) effects of s-ethyl cysteine (SEC), and s-propyl cysteine (SPC) in kidney of diabetic mice were examined. SEC and SPC at 1 and 2 g/L were added to the drinking water for 12 wk. Results showed that diabetic mice with SEC or SPC intake had significantly higher final body weight, lower kidney weight, lower levels of plasma glucose, urinary albumin (UA), and urinary creatinine (UC) (p < 0.05), in which dose-dependent effects were observed in reducing plasma glucose, UA, and UC (p < 0.05). The intake of these compounds significantly and dose-dependently decreased the levels of plasma glycated hemoglobin (HbA1c), renal carboxymethyllysine and urinary glycated albumin (p < 0.05). SEC or SPC intake significantly and dose-dependently diminished renal aldose reductase (AR) activity and enhanced glyoxalase I (GLI) activity (p < 0.05); also significantly decreased renal sorbitol and fructose concentrations (p < 0.05). The intake of SEC or SPC significantly lowered renal VEGF level (p < 0.05), and caused dose-dependent downregulation in AR mRNA expression, and upregulation in GLI mRNA expression (p < 0.05). Our present study suggests the supplement of SEC or SPC might be helpful for the prevention or treatment of diabetic kidney diseases via alleviating renal glycative injury.     

Antiinflammatory and antifibrogenic effects of s-ethyl cysteine and s-methyl cysteine in the kidney of diabetic mice

Protective effects of s-ethyl cysteine (SEC) and s-methyl cysteine (SMC) in kidney of diabetic mice were examined. SEC and SMC at 0.5, 1, 1.5, 2 g/L were added to the drinking water for 6 wk. Results showed that the intake of SEC or SMC alleviated body weight loss and urine output, as well as markedly decreased plasma blood urea nitrogen (BUN) and creatinine clearance (CCr) in diabetic mice (P < 0.05). The intake of SEC caused significantly dose-dependent increase in insulin and decrease in blood glucose, urinary albumin and type IV collagen (P < 0.05). SEC and SMC intake significantly and dose-dependently decreased malondialdehyde level and increased glutathione content in kidney (P < 0.05). The intake of these agents also increased renal GPx activity (P < 0.05), but there was no dose-dependent effect. SEC treatments dose-dependently decreased IL-6 and TNF-alpha levels, increased IL-4 and IL-10 levels, as well as upregulated IL-10 mRNA expression (P < 0.05). SMC treatments significantly suppressed renal IL-6 and TNF-alpha levels (P < 0.05), but did not affect IL-4 and IL-10 levels (P < 0.05). SEC or SMC intake significantly suppressed renal TGF-beta1 level and renal PKC activity (P < 0.05); however, only SEC treatments showed dose-dependent effect. SEC and SMC treatments significantly down-regulated mRNA expression of renal TGF-beta1 (P < 0.05), only SEC treatments had dose-dependent effects. Based on the observed antioxidative, antiinflammatory, and antifibrogenic effects, the supplement of SEC or SMC might be helpful for the prevention or treatment of diabetic kidney diseases.