Comparative pharmacokinetics of purified flaxseed and associated mammalian lignans in male Wistar rats.

Consumption of flaxseed lignans is associated with various health benefits; however, little is known about the bioavailability of purified lignans in flaxseed. Data on their bioavailability and hence pharmacokinetics (PK) are necessary to better understand their role in putative health benefits. In the present study, we conducted a comparative PK analysis of the principal lignan of flaxseed, secoisolariciresinol diglucoside (SDG), and its primary metabolites, secoisolariciresinol (SECO), enterodiol (ED) and enterolactone (EL) in rats. Purified lignans were intravenously or orally administered to each male Wistar rat. SDG and its primary metabolites SECO, ED and EL were administered orally at doses of 40, 40, 10 and 10 mg/kg, respectively, and intravenously at doses of 20, 20, 5 and 1 mg/kg, respectively. Blood samples were collected at 0 (pre-dose), 5, 10, 15, 20, 30 and 45 min, and at 1, 2, 4, 6, 8, 12 and 24 h post-dosing, and serum samples were analysed. PK parameters and oral bioavailability of purified lignans were determined by non-compartmental methods. In general, administration of the flaxseed lignans SDG, SECO and ED demonstrated a high systemic clearance, a large volume of distribution and short half-lives, whereas administration of EL at the doses of 1 mg/kg (intravenously) and 10 mg/kg (orally administered) killed the rats within a few hours of dosing, precluding a PK analysis of this lignan. PK parameters of flaxseed lignans exhibited the following order: systemic clearance, SDG < SECO < ED; volume of distribution, SDG < SECO < ED; half-life, SDG < ED < SECO. The percentage of oral bioavailability was 0, 25 and < 1 % for SDG, SECO and ED, respectively.

Chemical profiling of lentil (Lens culinaris Medik.) Cultivars and isolation of compounds.

A high-performance liquid chromatography method was developed to obtain fingerprints of secondary metabolites of 12 lentil cultivars grown under the same environmental condition. Extracts (100% methanol and methanol-water (1:1)) were analyzed by RP-HPLC. Full photodiode array (191-360 nm) data were collected and used for cluster analysis. Methanol and methanol-water extracts showed slightly different clustering patterns. In the dendogram of methanol extracts, CDC Richlea appeared as an isolated group, whereas Indianhead was the isolated group in methanol-water extracts. The cultivar CDC Milestone was selected for further evaluation because of the presence of three peaks (8.9, 16.7, and 32.7 min) that were absent in other cultivars or present in very small amounts. Chromatographic separations of the methanol extract afforded several compounds including the novel 4-chloro-1H-indole-3-N-methylacetamide (13) as well as itaconic acid (3), arbutin (5), gentisic acid 5-O-[beta-d-apiofuranosyl-(1-->2)-beta-d-xylopyranoside] (9), and (6S,7Z,9R)-9-hydroxymegastigma-4,7-dien-3-one-9-O-beta-d-apiofuranosyl-(1-->2)-beta-d-glucopyranoside (14), which are described for the first time from lentils. Structures were determined by high-resolution NMR experiments.

Production of angiotensin I-converting enzyme inhibitory peptides from defatted canola meal.

To simplify the method of ACE-inhibitory peptide production, defatted canola meal was subjected to enzymatic proteolysis. Alcalase 2.4 L and protease M "Amano" were found to be the most efficient enzymes in releasing ACE-inhibitory peptides from canola proteins among 13 tested enzymes. The IC(50) values of canola protein hydrolysates ranged from 18.1 to 82.5 microg protein/mL. Differences in ACE-inhibitory activities of various protein hydrolysates reflected varied enzyme specificities. A positive correlation was determined between ACE-inhibitory activity and the degree of hydrolysis (r=0.5916, p<0.001). Ion-exchange chromatography of canola protein hydrolysate increased the protein content greater than 95% without loss of ACE-inhibitory activity. This fraction was resistant to the degradation of gastrointestinal enzyme and ACE during in vitro incubation and may be a useful ingredient in the formulation of hypotensive functional food products.

Isoflavone content and its potential contribution to the antihypertensive activity in soybean Angiotensin I converting enzyme inhibitory peptides.

A soybean angiotensin I converting enzyme (ACE) inhibitory peptide fraction was reported to have antihypertensive activity in a rat study. The purpose of the present study was to examine if the presence of isoflavones in the soybean ACE inhibitory peptide fraction may contribute to the blood-pressure-lowering property. The isoflavone concentration in soybean samples was analyzed on a C 18 reverse-phase column using a two-step gradient solvent system. Producing soybean hydrolysate led to a nearly 40% loss of isoflavones compared with the original soybean flour, but the isoflavone composition did not change and the dominant isoflavone chemicals remained as 6''-O-malonylgenistin and 6''-O-malonyldaidzin. Ion exchange chromatography affected significantly both the content and the composition of the isoflavones. The dominant isoflavones in the ion-exchanged fraction were aglycones and nonacylated isoflavones, accounting for 95.8% of the total amount of 987.7 microg/g. It was calculated that the isoflavone content in the soybean ACE inhibitory peptide fraction was 25 times less than the minimal effective isoflavone dose reported. In vitro study also showed that adding isoflavones into both soybean flour hydrolysate and soybean ACE inhibitory peptide samples to a concentration of as high as 31.5% (w/w) did not affect ACE inhibitory activity (IC 50 values). The findings along with previously published results indicated that the contribution of isoflavones in soybean ACE inhibitory peptide fraction to the blood-pressure-lowering property in a short-term feeding study might be negligible.

The effect of flax seed cultivars with differing content of alpha-linolenic acid and lignans on responses to mental stress.

BACKGROUND: Phytoestrogens offer a possible alternative to hormone replacement therapy. Flax seed contains large quantities of a phytoestrogen precursor, secoisolariciresinol diglucoside (SDG), as well as large quantities of alpha-linolenic acid; these factors may be protective against vascular disease. We have previously shown that the rise in blood pressure during mental stress is a strong predictor of atherosclerosis progression. METHODS: 35 postmenopausal women with vascular disease, 62 +/- 8 years of age, were treated in a random-sequence double-blind Latin square crossover study comparing three strains of flax seed: Flanders (low in lignan and high in alpha-linolenic acid), Linola 989 (high in lignan and low in alpha-linolenic acid) and AC Linora (intermediate in both lignan and alpha-linolenic acid). RESULTS: Compared to the pre-treatment baseline diet, all three strains of flax significantly reduced blood pressure during mental stress induced by a frustrating cognitive task (Stroop color-word interference task) (p = 0.004). Linola 989, the strain highest in lignan and lowest in alpha-linolenic acid, was associated with the least increase in peripheral resistance during stress, the greatest reduction in plasma cortisol during stress and the smallest increase in plasma fibrinogen during mental stress. CONCLUSION: Flax phytoestrogens ameliorate certain responses to stress and thus may afford protection against atherosclerosis; this hypothesis should be tested in clinical trials.