Omega-3 fatty acids from fish oils and cardiovascular disease

Fish and fish oils contain the omega-3 fatty acids known as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Epidemiological studies have shown an inverse relation between the dietary consumption of fish containing EPA/DHA and mortality from coronary heart disease. These relationships have been substantiated from blood measures of omega-3 fatty acids including DHA as a physiological biomarker for omega-3 fatty acid status. Controlled intervention trials with fish oil supplements enriched in EPA/DHA have shown their potential to reduce mortality in post-myocardial infarction patients with a substantial reduction in the risk of sudden cardiac death. The cardioprotective effects of EPA/DHA are widespread, appear to act independently of blood cholesterol reduction, and are mediated by diverse mechanisms. Their overall effects include anti-arrhythmic, blood triglyceride-lowering, anti-thrombotic, anti-inflammatory, endothelial relaxation, plus others. Current dietary intakes of EPA/DHA in North America and elsewhere are well below those recommended by the American Heart Association for the management of patients with coronary heart disease. (Mol Cell Biochem 263: 217–225, 2004)     

真菌发酵生产鱼油特征脂肪酸

DHA和EPA是鱼油的特征脂肪酸,具有调整血脂、改善大脑功能和维持正常视力等重要作用.一直以来,其来源主要是海产鱼油.近年研究发现许多微生物的脂质中也含有DHA和EPA,特别是一些低等真菌含量甚为丰富,利用其发酵生产DHA和EPA替代鱼油资源具有广阔的前景.阐述了能产生EPA,DHA的真菌及其合成途径和发酵影响因素.     

植物激素对破囊壶菌生长与产DHA的影响

研究了植物激素对破囊壶菌(Thraustochytrium roseum) MF2产DHA的影响作用。实验结果表明：植物激素对T.roseum MF2的生长和产DHA有很大影响;赤霉素(GA)能促进DHA的合成,6苄基腺嘌呤(BA)能显著促进T.roseum　MF2的生长,二者的配合使用能明显增加DHA的产量;培养基中适宜的添加量为2mg/L GA和3mg/L BA,可使DHA产量达到982mg/L。     

Effect of culture conditions on growth and production of docosahexaenoic acid (DHA) usingThraustochytrium aureum ATCC 34304

Environmental and medium factors were investigated as basic data for optimizing DHA production when usingThraustochytrium aureum. To study the effect of environmental conditions, the rotation speed and culture temperature were, changed. Plus the trend of the growth characteristics, lipid content in the biomass, and DHA content in lipids were evaluated according to various initial glucose concentrations. The biomass, lipid, and DHA analyses showed that the physiological characteristics ofT. aureum were closely related with the environmental and medium conditions, as in the case of other marine microorganisms. For example, a low rotation speed of 50 rpm lowered the cell growth rate as well as the DHA content in the lipids. A low temperature had a negative effect on the cell growth, yet a positive effect on the lipid content in the biomass. Different initial glucose concentrations had no effect on the lipid content in the biomass or DHA content in the lipids, yet did affect the cell growth. Accordingly, these results show that environmental and medium factors must be synthetically considered in order to optimize DHA production when usingT. aureum.     

Effects of Chemical Modification of Arginine Residues Outside the Active Site Cleft of Ricin A-Chain on Its RNA N-Glycosidase Activity for Ribosomes

Ricin A-chain, a protein that inactivates ribosomes by a specific RNA N-glycosidase activity, has been shown to be inactivated by chemical modification of a few arginine residues. When two or fewer arginine residues in the A-chain were modified with [¹⁴C]phenylglyoxal, arginines at positions of 193, 196, 213, and 234/235 were found to be modified, from amino acid compositions and radioactivities of the modified peptides that were obtained by cyanogen bromide cleavage followed by tryptic and chymotryptic digestion. All these arginines have side chains outside the active site cleft; the side chain of Arg213 is adjacent to the edge of the cleft, while other modified arginines are located on the opposite side of the cleft. Kinetic analysis showed that the modification of two arginine residues caused a 8-fold loss in k_cat with a 3-fold increase in K_m, suggesting that this modification mainly decrease the rate of depurination with an additional effect on the affinity for ribosomes. Neither the environment of tryptophan 211 at the bottom of the cleft nor an interaction of adenine with the cleft was changed by this modification, as judged by fluorescence spectroscopy, suggesting that a conformational change of the catalytic site does not occur upon the modification. These results, taken together with other works, suggest that some of the above arginine residues outside the active site cleft may additively contribute to the catalysis of depurination and/or the initial formation of the A-chain/ribosome complex.     

Dietary supplementation of N-3 fatty acids and hydroperoxide levels in rat retinas

Docosahexaenoic acid (DHA) plays an important role in visual and neural development in mammals. In the present study, effect of dietary supplementation with n-3 fatty acids, primarily docosahexaenoic acid (DHA) with high purity, on the fatty acid composition of photoreceptor cells of young rats (fed from 4 weeks) was investigated. DHA in rod outer segment (ROS) membranes was significantly increased in the group of high DHA feeding (9.69% total energy). Other n-3 fatty acids (α-linolenic acid (ALA) and eicosapentaenoic acid (EPA)) included in the diets with DHA (0.95%～5.63% total energy) also significantly increased the proportion of DHA compared with the linoleic acid diet groups. However, the proportions of arachidonic acid (ARA) and other long chain n-6 fatty acids (22:4n6 and 22:5n6) were suppressed in these n-3 fatty acids-fed groups. Phospholipid hydroperoxides in ROS membranes were determined using a highly sensitive analytical technique, chemiluminescence-high performance liquid chromatography (CL-HPLC). There was no increasing tendency in the hydroperoxide levels of ROS membranes containing high content of DHA, and phosphatidylethanolamine hydroperoxide (PEOOH) was much lower than phosphatidylcholine hydroperoxide (PCOOH) under normal light conditions, which implies that DHA supplementation does not much affect the peroxidizability of ROS membranes in vivo. But UV irradiation on separated ROS membranes accelerated the formation of phospholipid hydroperoxides in high DHA feeding rats, and PEOOH was produced more efficiently than PCOOH in vitro.     

Access to new highly potent antileukemia,antiviral and antimalarial agents via hybridization of natural products (homo)egonol,thymoquinone and artemisinin

Hybridization of natural products has high potential to further improve their activities and may produce synergistic effects between linked pharmacophores. Here we report synthesis of nine new hybrids of natural products egonol, homoegonol, thymoquinone and artemisinin and evaluation of their activities against P. falciparum 3D7 parasites, human cytomegalovirus, sensitive and multidrug-resistant human leukemia cells. Most of the new hybrids exceed their parent compounds in antimalarial, antiviral and antileukemia activities and in some cases show higher in vitro efficacy than clinically used reference drugs chloroquine, ganciclovir and doxorubicin. Combined, our findings stress the high potency of these hybrids and encourages further use of the hybridization concept in applied pharmacological research.     

One-pot synthesis of bioactive cyclopentenones from α-linolenic acid and docosahexaenoic acid

Oxidation products of the poly-unsaturated fatty acids (PUFAs) arachidonic acid, α-linolenic acid and docosahexaenoic acid are bioactive in plants and animals as shown for the cyclopentenones prostaglandin 15d-PGJ₂ and PGA₂, cis-(+)-12-oxophytodienoic acid (12-OPDA), and 14-A-4 neuroprostane. In this study an inexpensive and simple enzymatic multi-step one-pot synthesis is presented for 12-OPDA, which is derived from α-linolenic acid, and the analogous docosahexaenoic acid (DHA)-derived cyclopentenone [(4Z,7Z,10Z)-12-[[-(1S,5S)-4-oxo-5-(2Z)-pent-2-en-1yl]-cyclopent-2-en-1yl] dodeca-4,7,10-trienoic acid, OCPD]. The three enzymes utilized in this multi-step cascade were crude soybean lipoxygenase or a recombinant lipoxygenase, allene oxide synthase and allene oxide cyclase from Arabidopsis thaliana. The DHA-derived 12-OPDA analog OCPD is predicted to have medicinal potential and signaling properties in planta. With OCPD in hand, it is shown that this compound interacts with chloroplast cyclophilin 20-3 and can be metabolized by 12-oxophytodienoic acid reductase (OPR3) which is an enzyme relevant for substrate bioactivity modulation in planta.     

High-fat diet-induced lipidome perturbations in the cortex,hippocampus, hypothalamus,and olfactory bulb of mice

Given their important role in neuronal function, there has been an increasing focus on altered lipid levels in brain disorders. The effect of a high-fat (HF) diet on the lipid profiles of the cortex, hippocampus, hypothalamus, and olfactory bulb of the mouse brain was investigated using nanoflow ultrahigh pressure liquid chromatography-electrospray ionization-tandem mass spectrometry in the current study. For 8?weeks, two groups of 5-week-old mice were fed either an HF or normal diet (6 mice from each group analyzed as the F and N groups, respectively). The remaining mice in both groups then received a 4-week normal diet. Each group was then subdivided into two groups for another 4-week HF or normal diet. Quantitative analysis of 270 of the 359 lipids identified from brain tissue revealed that an HF diet significantly affected the brain lipidome in all brain regions that were analyzed. The HF diet significantly increased diacylglycerols, which play a role in insulin resistance in all regions that were analyzed. Although the HF diet increased most lipid species, the majority of phosphatidylserine species were decreased, while lysophosphatidylserine species, with the same acyl chain, were substantially increased. This result can be attributed to increased oxidative stress due to the HF diet. Further, weight-cycling (yo-yo effect) was found more critical for the perturbation of brain lipid profiles than weight gain without a preliminary experience of an HF diet. The present study reveals systematic alterations in brain lipid levels upon HF diet analyzed either by lipid class and molecular levels.     

Effect of dietary supplementation with a highly pure and concentrated docosahexaenoic acid (DHA) supplement on human sperm function

The aim of this study was to evaluate the possible beneficial effects of diet supplementation with a highly concentrated and purified docosahexaenoic acid (DHA) formula on human sperm function. We performed a prospective, randomized, double blind, placebo-controlled intervention study. One-hundred eighty human semen samples from sixty infertile patients recruited in a private assisted reproduction center were included. All samples were examined according to World Health Organization guidelines. We analyzed macroscopic and microscopic sperm parameters, oxidative stress, apoptosis, lipid peroxidation, mitochondrial membrane potential and DNA fragmentation before and after supplementation with different DHA daily doses (0.5, 1 and 2?g) or placebo for 1 and 3 months. No differences were found in traditional sperm parameters except for progressive sperm motility, with a significant increase after DHA ingestion after the first month with 1 or 2?g doses and after 3 months with 0.5?g of DHA. This effect was more evident in asthenozoospermic patients. No differences were found in any molecular semen parameter except oxidative stress, in which a slight benefit was observed after DHA treatment. In conclusion, this study support previous indications that highlight the importance of DHA supplementation as a means of improving sperm quality in asthenozoospermic men.