The n-3 Polyunsaturated Fatty Acids Supplementation Improved the Cognitive Function in the Chinese Elderly with Mild Cognitive Impairment: A Double-Blind Randomized Controlled Trial.

OBJECTIVE: Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI. METHODS: Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules. The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests (BCAT). RESULTS: The mean age of participants was 71 years old, and 59% of the participants were men. n-3 PUFA supplementation was associated with improved total BCAT scores, perceptual speed, space imagery efficiency, and working memory (p < 0.01), but not with mental arithmetic efficiency or recognition memory (p > 0.05). Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed (p = 0.001), space imagery efficiency (p = 0.013), working memory (p = 0.018), and total BCAT scores (p = 0.000) in males. However, in females, the significant beneficial effects can only be observed in perceptual speed (p = 0.027), space imagery efficiency (p = 0.006), and total BCAT scores (p = 0.015)-not working memory (p = 0.113). CONCLUSION: n-3 PUFAs can improve cognitive function in people with MCI. Further studies with different fish oil dosages, longer intervention periods, and larger sample sizes should be investigated before definite recommendations can be made.

Influence of pomegranate seed oil and bitter melon aqueous extract on polyunsaturated fatty acids and their lipoxygenase metabolites concentration in serum of rats.

Competition with polyunsaturated fatty acids (PUFA) and an impact on eicosanoid biosynthesis may be one of mechanisms of conjugated linolenic acids (CLnA) action. The aim of this study was to investigate the influence of diet supplementation with pomegranate seed oil, containing punicic acid (PA)-one of CLnA isomers, and an aqueous extract of dried bitter melon fruits, administered separately or together, on PUFA and their lipoxygenase metabolites' concentration in serum of rats. Percentage share of fatty acids was diversified in relation to applied supplementation. PA was only detected in serum of pomegranate seed oil supplemented group, where it was about 1%. Cis-9, trans-11 conjugated linoleic acid (rumenic acid, RA) level tended to increase in group supplemented simultaneously with both dietary supplements whereas its highest share in total fatty acids pool was detected in group receiving solely bitter melon dried fruits aqueous extract. This indicates that consumption of bitter melon tea significantly increased RA content in fatty acids pool in serum. However, pomegranate seed oil elevated procarcinogenic 12-hydroxyeicosatetraenoic acid concentration. Taking into account that pomegranate seed oil and bitter melon dried fruits are dietary supplements accessible worldwide and willingly consumed, the biological significance of this phenomenon should be further investigated. We presume, that there may be a need for some precautions concerning the simultaneous use of these products.

[The correction of disorders in arachidonic acid metabolism in coronary spasm of an immune origin]. / Korektsiia porushen' metabolizmu arakhidonovoï kysloty pry koronarospazmi imunnoho henezu.

The effect of phosphocreatine and hydroxamate-linoleate (an inhibitor of lipoxigenase) on development of the pathologic process in coronary vessels with immune (cytotoxic) injury of the heart was studied in the experiments on narcotized dogs. Development of the immune response after administration of cardiac serum resulted in development of large transmural damage of the left ventricle myocardium, increased resistance of coronary vessels and changed coronary vascular reactions, which correlates with changes in arachidonic acid metabolism. Experimental data described in this report demonstrate the efficiency of membrane coronary vessels stabilization and inhibition of a lipoxygenase pathway in arachidonic acid metabolism in protection of immune damage of the heart and coronary vessels.

Antiplatelet constituents of garlic and onion.

We have identified three main antiplatelet constituents, namely adenosine, allicin and paraffinic polysulfides in both garlic and onion. Adenosine and allicin both inhibited platelet aggregation without affecting cyclooxygenase and lipoxygenase metabolites of arachidonic acid. The trisulfides inhibited platelet aggregation as well as thromboxane synthesis along with induction of new lipoxygenase metabolites. The data indicate that the observed in vivo antiplatelet effects of ingesting onion and garlic are attributable more to the adenosine than to the allicin and paraffinic polysulfide constituents.

Extracts from two frequently consumed spices--cumin (Cuminum cyminum) and turmeric (Curcuma longa)--inhibit platelet aggregation and alter eicosanoid biosynthesis in human blood platelets.

In the traditional Indian system of medicine, Ayurveda, several spices and herbs are claimed to possess medicinal properties, such as being antithrombotic, antiatherosclerotic, hypolipidemic, anti-inflammatory etc. Earlier we have reported that extracts from several spices behave as antiaggregatory agents and inhibit eicosanoid synthesis. Similar studies with extracts prepared from cumin (Cuminum cyminum) and turmeric (Curcuma longa) were undertaken. Ethereal extract of both cumin and turmeric inhibited arachidonate-induced platelet aggregation. Extracts from these spices inhibited thromboxane B2 production from exogenous (14C) arachidonic acid (AA) in washed platelets; a simultaneous increase in the formation of lipoxygenase-derived products was observed. Less TxB2 was produced in blood samples treated with turmeric extract when they were allowed to clot. Turmeric extract inhibited incorporation of (14C)AA into platelet phospholipids and deacylation of AA-labelled phospholipids on stimulation with calcium ionophore A23187. Cumin extract was devoid of such effects. Extracts from the two spices reduced the formation of (14C)TxB2 from AA-labelled platelets when they were challenged with A23187. The anti-inflammatory property of turmeric may, in part, be explained by its effect on eicosanoid biosynthesis.

Isolation and effects of some garlic components on platelet aggregation and metabolism of arachidonic acid in human blood platelets.

Effects of aqueous extract of garlic, of materials extracted in two organic solvents, viz., ether and chloroform in succession, and of some fractions obtained after TLC of the aqueous extract were examined on platelet aggregation induced by several aggregating agents. Their effects were also investigated on the formation of thromboxane and lipoxygenase products from endogenous arachidonic acid in intact platelets. The aqueous extract inhibited aggregation induced by all aggregating agents and so did the materials extracted in two organic solvents. Only two fractions obtained from TLC of the aqueous garlic extract were examined for effects on epinephrine- and arachidonic acid (AA)-induced aggregation; they were found to be antiaggregatory. The material extracted in ether (MEE) inhibited the incorporation of labelled AA into platelets in platelet-rich plasma. Garlic extracts (MEE and material extracted in chloroform, MEC) at higher dosage inhibited the degradation of platelet phospholipids and reduced the formation of thromboxane (TxB2) and lipoxygenase-derived products from labelled platelets. The two organic extracts at low dosage, while not affecting the degradation of platelet phospholipids, inhibited the cyclooxygenase and lipoxygenase enzymes. A concomitant increase in the amount of released AA was observed in the treated platelets. Similar effects in relation to dosage were observed with the aqueous extract of garlic.

Altered platelet lipoxygenase activity in patients with low selenium.

1. Arachidonic acid metabolism through the lipoxygenase pathway in platelets was investigated in 11 patients with low selenium (Se) nutritional status and compared with 14 patients with a normal Se status. 2. Plasma and whole blood Se levels, as well as plasma, whole blood and platelet glutathione peroxidase (GSHPx) activity, were measured in both groups and found to be significantly lower in the group with low Se status. 3. Studies on [14C]arachidonic acid stimulated platelets demonstrated that reduced conversion of the active metabolite 12-hydroperoxyeicosatetraenoic acid to 12-hydroxyeicosatetraenoic acid occurred in patients with low Se nutrition. 4. Changes in [14C]arachidonic acid metabolism are attributed to reduced activity of the seleno-enzyme GSHPx. The effects of other factors cannot be entirely excluded.

Evidence for the mechanism by which garlic inhibits platelet aggregation.

Aqueous extract of garlic inhibited aggregation induced by ADP, collagen, arachidonate (AA), epinephrine and calcium ionophore A23187 in a dose-dependent manner. In an attempt to clarify the mechanism of inhibition of aggregation, metabolism of arachidonic acid in platelets was examined in the presence of garlic extract. It was found that: garlic reduced the formation of thromboxane from exogenous AA; garlic inhibited the phospholipase activity; garlic inhibited the formation of thromboxane and lipoxygenase products formed in platelets prelabelled with AA; and garlic inhibited the incorporation of arachidonate into platelet phospholipids. These effects may explain, in part, inhibition of platelet aggregation. Further, since garlic was also effective in inhibiting aggregation induced by calcium ionophore A23187 it may be suggested that the antiaggregation effect may be related to intraplatelet mobilization of calcium. Inhibition of epinephrine-induced aggregation by garlic extract may suggest that it may be inhibiting uptake of calcium into platelets thereby lowering cytosolic calcium concentrations. Thus garlic appears to be in possession of components which might exert their effects at various stages involved in the process of platelet aggregation.

Interaction of non-steroidal anti-inflammatory drugs on platelet cyclo-oxygenase and lipoxygenase activity.

Non-steroidal anti-inflammatory drugs inhibit platelet cyclo-oxygenase activity. This study shows that salicylate, diflunisal, sulphinpyrazone and indomethacin prevent the in vivo inhibitory effect of aspirin on cyclo-oxygenase activity as measured by the formation of malondialdehyde and thromboxane B2, two products of platelet arachidonic acid metabolism. Salicylate also prevents the inhibitory effect of indomethacin. All these drugs therefore appear to interact with the same site on platelet cyclo-oxygenase. Since salicylate is inactive by itself on this platelet enzyme and diflunisal and sulphinpyrazone were used at ineffective doses, it is suggested that they interact with aspirin (or indomethacin) at a supplementary binding site, rather than directly on the substrate active site. Interaction with this putative supplementary site is necessary but not sufficient for the efficacy of these drugs as cyclo-oxygenase inhibitors. Acetylation by aspirin of the active site appears to be secondary to binding of the salicylate moiety to the supplementary site. Sodium salicylate is also inactive on platelet lipoxygenase. It prevents the inhibition of cyclo-oxygenase induced by aspirin, but does not counteract the inhibitory effect of 5, 8, 11, 14-eicosatetraynoic acid on both enzymes. It also fails to interfere with the inhibitory activity of nordihydroguaiaretic acid on lipoxygenase. These data confirm that, unlike eicosatetraynoic acid, nonsteroidal anti-inflammatory drugs interact with a site on cyclo-oxygenase distinct from the catalytic site, although related to it. Such a supplementary binding site is lacking on lipoxygenase.

Hydroperoxy fatty acid formation in selenium deficient rat platelets: coupling of glutathione peroxidase to the lipoxygenase pathway.

After incubation with [1-14C]-arachidonic acid, washed platelets from selenium deficient rats produced a sevenfold greater amount of 12-hydroperoxytetraenoic acid than platelets from control animals. When stimulated with either arachidonic acid or t-butyl-hydroperoxide, antimycin-A1 treated platelets from the deficient rats also converted markedly lower amounts of [1-14C]-glucose to [14C]-CO2 than platelets from control rats. These results indicate a significant role for platelet selenium-dependent glutathione peroxidase in the enzymatic reduction of platelet-produced hydroperoxides.

Salicylate fails to prevent the inhibitory effect of 5,8,11,14-eicosatetraynoic acid on human platelet cyclo-oxygenase and lipoxygenase activities.

Sodium salicylate is inactive both on cyclo-oxygenase and lipoxygenase prepared from human platelets. It prevents the inhibition of cyclo-oxygenase induced by aspirin, but does not counteract the inhibitory effect of 5,8,11,14-eicosatetraynoic acid on both enzymes. It also fails to interfere with the inhibitory activity of nordihydroguaiaretic acid on lipoxygenase. These data indicate that, unlike eicosatetraynoic acid, non-steroidal anti-inflammatory drugs interact with a site on cyclo-oxygenase distinct from the catalytic site, although related to it. Such a supplementary binding site is lacking on lipoxygenase.

Vitamin E and the inhibition of platelet lipoxygenase.

Lipoxygenase was assayed by the formation of hydroxy-eicosatetraenoic acid (HETE) from arachidonic acid in human and rabbit washed platelets. Platelets from vitamin E-supplemented rabbits had much less lipoxygenase activity than platelets from either vitamin E-deficient or normal rabbits. Human and rabbit platelets preincubated with vitamin E had lowered lipoxygenase activity. These data show that vitamin E inhibits platelet lipoxygenase. Vitamin E and vitamin E acetate, in vitro, were equally effective inhibitors of lipoxygenase. Tween 20, in vitro, was a highly effective inihbitor of lipoxygenase. These data show that vitamin E functions, in vitro, as a surfactant in the inhibition of platelet lipoxygenase.