| On the other hand, the predominant form of vitamin E in our diets is gamma tocopherol (ð-TOH) and recent studies show that several of the non-antioxidant physiological functions of vitamin E may be specific to ð-TOH. Yet, this vitamer occurs in blood and tissues at much lower concentrations than a-TOH. This is because a substantial portion of ingested ð-TOH is excreted in urine as its 3'-carboxychromanol metabolite whereas only a small fraction of a-TOH is excreted by a similar mechanism. Administration of sesame oil or purified sesamin results in elevated tocopherol concentrations in rats and humans with the effect greater toward ð-TOH. Sesamin is a potent inhibitor of tocopherol-hydroxylase, one of the key enzymes in tocopherol catabolism, in hepatocyte cultures, rat and human liver microsomes.
Although a-TOH failed to afford protection against coronary heart disease in human clinical trials, gin one of the studies, interestingly, vitamin E appeared to offer protection, but only when taken up from the diet and not when taken as supplements. Further, a clinical evaluation of individuals suffering from coronary heart disease showed decreased serum levels of ð-TOH, but not a-TOH indicating a critical role for ð-TOH in the prevention of cardiovascular diseases. Because a-TOH supplementation suppresses ð-TOH18, co-administration of sesamin may retard this effect and make this vital vitamin more bioavailable.
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Sesamin has a unique lipid lowering property by 1) increasing the rate of fatty acid oxidation, 2) decreasing the rate of fatty acid synthesis, and 3) reducing cholesterol absorption.
Fatty acid oxidation: Seasmin appears to be most potent inducer of hepatic fatty acid oxidation among the various natural products. Dietary sesamin increased the mitochondrial and peroxisomal fatty acid oxidation rate dose-dependently. A diet containing 0.5% sesamin doubled the mitochondrial oxidation rate while the peroxisomal oxidation rate was increased 10-fold, in rats19. Sesamin strongly induced the activities and the gene expression of the various hepatic enzymes involved in fatty acid oxidation through peroxisome proliferator activated receptors (PPARs). This effect was seen at dietary levels as low as 0.1%. A recent DNA microarray study indicated that sesamin strongly induced the gene expression of enzymes involved in fatty acid oxidation20. Ingestion of sesamin dissolved in olive oil up-regulated the expression of 38 genes, 16 of which encode proteins possessing lipid lowering function, and 16 of which encode proteins possessing a xenobiotic/endogenous substance metabolizing function. In particular, sesamin significantly increased the expression of ß-oxidation-associated enzymes in the peroxisomes, and auxiliary enzymes required for degradation, in the mitochondria. Interestingly, sesamin also induced the gene for the alcohol-metabolizing enzyme, aldehyde dehydrogenase. These results indicate that sesamin regulates the metabolism of lipids, xenobiotics, and alcohol at the mRNA level.
Fatty acid synthesis: Sesamin also has a favorable effect on hepatic fatty acid synthesis in rats. A diet containing 0.1% sesamin caused a 20-40% decrease in the activity and mRNA level of the enzymes involved in fatty acid synthesis, except for the malic enzyme. The effect was dose-dependent. Sterol regulatory element-binding proteins (SREBPs) regulate the gene expression of the enzymes involved in fatty acid and cholesterol biosynthesis. SREBP-1 regulate the gene expression of fatty acid synthesis enzymes while SREBP-2 is involved in cholesterol biosynthesis. Diets containing 0.1 to 0.2% sesamin caused a 30% decrease in the SREBP-1 mRNA levels. This effect, again, was dose-dependent.
Reduced fatty acid synthesis, coupled with increased fatty acid oxidation, can potentially reduce hepatic triacylglycerol (TG) synthesis and consequently decrease the assembly and secretion of TG-rich lipoproteins. This effect, indeed, has been seen in rat liver. Dietary sesamin caused a 40% decrease in the rate of hepatic TG secretion. This may account for the lipid-lowering effect of sesamin.
Inhibition of cholesterol absorption and synthesis: Sesamin reduced the serum and liver cholesterol levels in experimental animals. The hypercholesterolemic activity of sesamin can at least in part be explained by the inhibition of the intestinal absorption of cholesterol as reflected by significant reduction in cholesterol in the thoracic lymph. In addition, sesamin reduced the activity of HMG-CoA reductase in liver microsomes, suggesting direct inhibition of the enzyme by sesamin. The study results also suggested increased catabolism of cholesterol. Sesamin is thought to interfere with cholesterol absorption by reducing the miscellar solubility of cholesterol which correlates with intestinal cholesterol absorption. The dual effects of blocking cholesterol synthesis as well as intestinal absorption makes sesamin a unique cholesterol lowering agent.
Inhibition of ?-5 desaturase: A number of studies demonstrate that sesamin supplementation results in significant inhibition of desaturation of n-6 polyunsaturated fatty acids (PUFA), but not n-3 PUFA. Therefore, consumption of sesamin could increase the production of the less inflammatory 1-series prostaglandins and reduce the production of proinflammatory 2-series prostanoids. Though no studies have explored this possibility, ingestion of sesamin may enhance the conversion of alpha linolenic acid to eicosapentaenoic acid (EPA), which conversion is rather sluggish in humans. A recent study23 investigated the effect of tube feeding of emulsions of safflower oil or linseed oil with sesamin (SO+ and LO+) or without sesamin (SO and LO) on liver fatty acid composition and on endotoxin-induced production of tumor necrosis factor-a (TNF-a), prostaglandin E2, 6-keto-prostaglandin F1a by whole blood from rats. A significant accumulation of dihomo gamma linolenic acid (DGLA) with concomitant reduction in the content of arachidonic acid (AA) was found only in the liver phospholipids of animals fed SO+ or LO+ due to inhibition of ?5-desaturation of n-6 fatty acids. These changes were associated with significant reductions in plasma concentrations of PG E2 in animals fed SO+ compared with those fed SO. Plasma concentrations of TNF-a were significantly lower in the animals fed LO+. There was also accumulation of EPA in animals fed LO diets. Therefore, consumption of sesamin-supplemented LO diets, resulting in significantly increased accumulation of EPA with a concomitant reduction in endotoxin-induced dienoic prostanoids and TNF-a, may have therapeutic potential to ameliorate clinical symptoms and complications that are secondary to excessive production of such proinflammatory mediators. These data also suggest that sesamin could inhibit cyclooxygenases which is responsible for the production of prostanoids.
Seasmin attenuates hypertension
There is accumulating evidence that an oxidative stress in vascular tissues is closely related to development of hypertensive diseases24,25. Vascular superoxide (O2-) production is increased in several animal models of hypertension and contributes to the development and perpetuation high blood pressure and endothelial dysfunction. Antihypertensive effect of sesamin has been demonstrated in several types of experimental hypertension models. In a deoxycorticosterone acetate (DOCA)-salt hypertensive animals, the increased production of O2- was normalized almost completely by feeding sesamin-containing diet26. Conventional drug therapy (reserpine, hydralazine, hydro-chlorothiazide) reduced hypertension, but did not suppress the increased O2- production, while significant suppression was achieved with sesamin27. Thus, the antioxidative property of sesamin at least partly may be responsible for the observed effect. It has been shown that, in the liver, sesamin is transformed into a catechol which has strong radical scavenging abilities.
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The high stability of sesame oil against oxidative deterioration is attributed to lignans present in its non-glyceride fraction (~0.5%). Sesamin, along with sesamoline and sesaminol constitute the major portion of the lignan fraction. Episesamin, a geometric isomer of sesamin and sesamol are found in processed oils, but not in crude sesame oil.
Alpha tocopherol is believed to be most important lipid soluble antioxidant in the body, protecting cell components from oxidative damage. Other biological functions have since been discovered, including cell signalling, gene expression, immune response and apoptosis. Yet high intakes of a-tocopherol (a-TOH) supplements has been shown to be detrimental with increase in all cause mortality in a meta analysis of previously published clinical trials6. Further, though initially thought as highly useful in preventing heart disease, a recent report indicate supplementation of patients suffering from diabetes mellitus or vascular disease with 400 IU of natural source a-tocopherol for 7 years resulted in an increased risk of heart failure.