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Antioxidant and antitumor effects of hydroxymatairesinol (HM-3000, HMR), a lignan isolated from the knots of spruce
Abstract
The antioxidant properties of hydroxymatairesinol (HM-3000) were studied in vitro in lipid peroxidation, superoxide and peroxyl radical scavenging, and LDL-oxidation models in comparison with the known synthetic antioxidants Trolox (a water-soluble vitamin E derivative), butylated hydroxyanisol (BHA) and butylated hydroxytoluene (BHT). On a molar basis HM-3000 was a more effective antioxidant than Trolox in all assays and more effective than BHT or BHA in lipid peroxidation and superoxide scavenging test. The in vivo antioxidative effect (evaluated as the weight gain of C57BL/6J mice fed an alpha-tocopherol-deficient diet) of HM-3000 (500 mg/kg per day) was comparable to that of DL-alpha-tocopherol (766 mg/kg per day). The antitumor activity of HM-3000 was studied in dimethylbenz[a]anthracene (DMBA)-induced rat mammary cancer. HM-3000 had a statistically significant inhibitory effect on tumor growth. Prevention of tumor formation was also evaluated in the Apc(Min) mice model, which develops intestinal polyps spontaneously. HM-3000 was given in diet at 30 mg/kg per day and decreased the formation of polyps and prevented beta-catenin accumulation into the nucleus, the pathophysiological hallmark of polyp formation in this mouse model. In short-term toxicity studies (up to 28 days) HM-3000 was essentially non-toxic when given p.o. to rats and dogs (daily doses up to 2000 and 665 mg/kg, respectively); HM-3000 was shown to be well absorbed (> 50% of the dose) and rapidly eliminated. In human studies HM-3000 has been given in single doses up to 1350 mg to healthy male volunteers without treatment-related adverse events. Rapid absorption from the gastrointestinal tract and partial metabolism to enterolactone in humans was demonstrated. In summary, HM-3000 is a safe, novel enterolactone precursor lignan with antioxidant and antitumor properties.
... Increased intake of dietary lignans is also associated with increased serum levels of sex hormonebinding globulin (SHBG) [10,[22][23][24] in postmenopausal women. In addition, lignans, particularly 7-HMR and ENL, demonstrate antioxidant properties [8,25] as well as antiproliferative activity in cancer cell lines [25]. An elevated level of 7-HMR has been described in the rat dimethylbenz[a]-anthraceneinduced breast cancer model to reduce tumor volume [25]. ...
... Increased intake of dietary lignans is also associated with increased serum levels of sex hormonebinding globulin (SHBG) [10,[22][23][24] in postmenopausal women. In addition, lignans, particularly 7-HMR and ENL, demonstrate antioxidant properties [8,25] as well as antiproliferative activity in cancer cell lines [25]. An elevated level of 7-HMR has been described in the rat dimethylbenz[a]-anthraceneinduced breast cancer model to reduce tumor volume [25]. ...
... In addition, lignans, particularly 7-HMR and ENL, demonstrate antioxidant properties [8,25] as well as antiproliferative activity in cancer cell lines [25]. An elevated level of 7-HMR has been described in the rat dimethylbenz[a]-anthraceneinduced breast cancer model to reduce tumor volume [25]. ...
Objective
7-Hydroxymaitairesinol (7-HMR) is a naturally occurring plant lignan found in whole grains and the Norway spruce (Piciea abies). The purpose of this study was to evaluate the bioavailability of a proprietary 7-HMR product (HMRlignan, Linnea SA, Locarno, Switzerland) through measurement of lignan metabolites and metabolic precursors.
Methods
A single-blind, parallel, pharmacokinetic and dose-comparison study was conducted on 22 post-menopausal females not receiving hormone replacement therapy. Subjects were enrolled in either a 36 mg/d (low-dose) or 72 mg/d dose (high-dose) regimen for 8 weeks. Primary measured outcomes included plasma levels of 7-HMR and enterolactone (ENL), and single-dose pharmacokinetic analysis was performed on a subset of subjects in the low-dose group. Safety data and adverse event reports were collected as well as data on hot flash frequency and severity.
Results
Pharmacokinetic studies demonstrated 7-HMR Cmax = 757.08 ng/ml at 1 hour and ENL Cmax = 4.8 ng/ml at 24 hours. From baseline to week 8, plasma 7-HMR levels increased by 191% in the low-dose group (p < 0.01) and by 1238% in the high-dose group (p < 0.05). Plasma ENL levels consistently increased as much as 157% from baseline in the low-dose group and 137% in the high-dose group. Additionally, the mean number of weekly hot flashes decreased by 50%, from 28.0/week to 14.3/week (p < 0.05) in the high-dose group. No significant safety issues were identified in this study.
Conclusion
The results demonstrate that HMRlignan is quickly absorbed into the plasma and is metabolized to ENL in healthy postmenopausal women. Clinically, the data demonstrate a statistically significant improvement in hot flash frequency. Doses up to 72 mg/d HMRlignan for 8 weeks were safe and well tolerated in this population.
... HMR is thus obtained in very high and convenient quantities, and large amounts are easily available in a suitable and standardized form, therefore circumventing some of the limitations which have so far hindered the accomplishment of studies with purified lignans. The chemical structure of HMR is closely related to the structure of matairesinol, and, as in the case of matairesinol, it represents therefore a highly efficient precursor of the mammalian lignan enterolactone in both animals and humans [9,10]. ...
... The pharmacological profile of HMR includes chemopreventive effects [7,[11][12][13], antioxidant properties [7,9], and mild proestrogenic activity [7,14,15]. In particular, HMR seems to be provided with strong antioxidative capacity independent from its estrogenic profile [7,8,15]. ...
... In particular, HMR seems to be provided with strong antioxidative capacity independent from its estrogenic profile [7,8,15]. Preliminary investigations also showed the ability of HMR to inhibit the oxidative burst of human monocytes/neutrophils [9]. The present study was therefore devised to investigate the effects of HMR on THP-1 cells, an established model of human monocytes [16], and on human polymorphonuclear leukocytes (PMNs). ...
The pharmacological profile of the lignan 7-hydroxymatairesinol (HMR/lignan, HMR) includes chemopreventive effects, antioxidant properties, and mild proestrogenic activity. The present study was devised to investigate the effects of HMR on THP-1 cells, an established model of human monocytes, and on human polymorphonuclear leukocytes (PMNs). In THP-1 cells, HMR concentration-dependently reduced LPS-stimulated tumor necrosis factor (TNF)-alpha secretion in the supernatant. HMR at low, sub-muM concentrations also reduced TNF-alpha mRNA, which was however enhanced by supra-muM concentrations of HMR. In human PMNs, HMR concentration-dependently reduced ROS production induced by either N-formyl-Met-Leu-Phe, phorbol myristate acetate or angiotensin II, as well as interleukin-8 production induced by either N-formyl-Met-Leu-Phe or angiotensin II. Results indicate that HMR is an effective inhibitor of both monocytic THP-1 cells and of human PMNs and warrant further studies to assess their relevance for the prevention and treatment of several conditions characterized by chronic systemic inflammation.
... 7S-HMR has been shown to metabolize to (−)-enterolactone by intestinal bacteria in rats and humans and to have chemopreventive effects on the development of DMBA induced mammary carcinoma in rats [7,8]. It has also been shown to have a chemopreventive effect in the ApcMin mice model of human familial adenomatous polyposis [9]. ...
... It has also been shown to have a chemopreventive effect in the ApcMin mice model of human familial adenomatous polyposis [9]. Furthermore, it has been shown to be a strong antioxidant and able to reduce the oxidation of LDL-particles in vitro [8]. It has been marketed as a nutritional supplement since 2006 [10]. ...
The preparation of 7R-HMR (allo-hydroxymatairesinol) is reported by: (a) NaBH4 kinetic reduction of 7R/7S diastereomeric mixture; and (b) epimerization of the C7 hydroxyl group by Mitsunobu reaction and subsequent ester hydrolysis. The availability of highly pure target compound (7R-HMR) made it possible to confirm the structure of the target compound and to complete the full spectroscopic characterization.
... Both TP and FF contain high levels of proteins, soluble and insoluble fibers which have many health benefits and can prevent diabetes and cardiovascular diseases (Agarwal & Rao, 2000;Prasad, 1997;Yuan, Rickard, & Thompson, 1999a, 1999b. Considering the health-related properties reported for TP and FF (Hall III, Tulbek, & Xu, 2006;Henson, Masakure, & Cranfield, 2008;Kangas et al., 2002). These ingredients were used to replace fat (Hautrive, Piccolo, Rodrigues, Campagnol, & Kubota, 2019), starch (Kianiani, Varidi, & Varidi, 2019), and allergen proteins like soy and wheat (Rabetafika, Van Remoortel, Danthine, Paquot, & Blecker, 2011) in the meat batters. ...
The present investigation deals with the textural properties, colloidal interactions, and morphology of emulsified meat systems in the presence of flaxseed flour (FF) and tomato powder (TP). The results displayed that the emulsifying capacity and texture of raw and cooked meat batters were significantly affected following the addition of TP and FF. The cooked emulsified sausages containing 3% of FF and 3% (w/w) of TP showed the highest values for hardness and cohesiveness, as compared to the control and 6% (w/w) of FF samples. The outcomes of mechanical shearing forces and SEM showed the formation of a gel-type matrix around the unabsorbed protein in TP-FF batters. These patterns were then confirmed by the higher values of GN° (van Gurp Palmen) associated with an increase in the elasticity and the molecular entanglement. In contrast, large fat globules, low entanglement, and protein cross-linking were observed in meat batters with 6% FF.
... Moreover, these phenolic compounds can contribute to both the the growth and development of plants [4]. It was reported that lignans had a wide range of biological activity, including immunosuppressive, anti-inflammatory, cardiovascular, antioxidant, antitumor, and antiviral effects [2,5]. ...
In this study, the antioxidant and antiradical properties of some phyto lignans (nordihydroguaiaretic acid, secoisolariciresinol, secoisolariciresinol diglycoside, and α-(-)-conidendrin) and mammalian lignans (enterodiol and enterolactone) were examined by different antioxidant assays. For this purpose, radical scavenging activities of phyto and mammalian lignans were realized by 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS•+) scavenging assay and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging assay. Additionally, the reducing ability of phyto and mammalian lignans were evaluated by cupric ions (Cu²⁺) reducing (CUPRAC) ability, and ferric ions (Fe³⁺) and [Fe³⁺-(TPTZ)2]³⁺ complex reducing (FRAP) abilities. Also, half maximal inhibitory concentration (IC50) values were determined and reported for DPPH• and ABTS•+ scavenging influences of all of the lignan molecules. The absorbances of the lignans were found in the range of 0.150–2.320 for Fe³⁺ reducing, in the range of 0.040–2.090 for Cu²⁺ reducing, and in the range of 0.360–1.810 for the FRAP assay. On the other hand, the IC50 values of phyto and mammalian lignans were determined in the ranges of 6.601–932.167 µg/mL for DPPH• scavenging and 13.007–27.829 µg/mL for ABTS•+ scavenging. In all of the used bioanalytical methods, phyto lignans, as secondary metabolites in plants, demonstrated considerably higher antioxidant activity compared to that of mammalian lignans. In addition, it was observed that enterodiol and enterolactone exhibited relatively weaker antioxidant activities when compared to phyto lignans or standard antioxidants, including butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), Trolox, and α-tocopherol.
... They have been used as components in the cosmetics, chemical and drug industries, and as constituent for Norway spruce resin salve used to heal wounds. The biological activity of lignans has been widely studied [4,6,7]. Lignans have been modified in the presence of nanometal (palladium) under acidic conditions [8][9][10]. ...
Lignans are bioactive compounds that are especially abundant in the Norway spruce (Picea abies L. Karst.) knotwood. By combining a variety of chromatographic, spectroscopic and imaging techniques, we were able to quantify, qualify and localise the easily extractable lignans in the xylem tissue. The knotwood samples contained 15 different lignans according to the gas chromatography-mass spectrometry analysis. They comprised 16% of the knotwood dry weight and 82% of the acetone extract. The main lignans were found to be hydroxymatairesinols HMR1 and HMR2. Cryosectioned and resin-embedded ultrathin sections of the knotwood were analysed with scanning transmission X-ray microscopy (STXM). Cryosectioning was found to retain only lignan residues inside the cell lumina. In the resin-embedded samples, lignan was interpreted to be unevenly distributed inside the cell lumina, and partially confined in deposits which were either readily present in the lumina or formed when OsO4 used in staining reacted with the lignans. Furthermore, the multi-technique characterisation enabled us to obtain information on the chemical composition of the structural components of knotwood. A simple spectral analysis of the STXM data gave consistent results with the gas chromatographic methods about the relative amounts of cell wall components (lignin and polysaccharides). The STXM analysis also indicated that a torus of a bordered pit contained aromatic compounds, possibly lignin.
... Magnesiumexerts its effect by relaxing the nervous system and muscles and overcoming the night terrors (Jyotsna, 2012). • Anti-cancerous properties:After consuming flaxseeds, secoisolariciresinol (SDG) present gets converted into active mammalian lignansenterodiolaandentero-lactone, which have the potential to reduce the growth of cancerous tumors, especially hormone-sensitive ones such as those of the cancers of breast (Brzezinski & Debi, 1998;Bruno, 2009), endometrium and prostate (Tour´e & Xueming, 2010).Lignans have an antioxidant activity and contributed to the anti-cancerous activity of flaxseed Kitts, Yuan, Wijewickrame, & Thompson, 1999;Yuan, Richard, & Thompson, 1999;Kangas, Saarinen, & Mutanen, 2002). Lignan, enterodiol and enterolactone are believed to be responsible for inhibiting the growth of human prostate cancerous cells (Lin, Awitzer, & Demark-Wahnefried, 2001). ...
Flaxseed (Linumusitatissimum L.) is one of the world’s oldest cultivated crops with evidence dating back thousands of years. Flaxseed is a premium food delivering high performance and is one of the richest sources of ω-3 fatty acids (α-linolenic acid) known
to man. Whole flaxseed, flaxseed oil, lignan precursors, and its mucilage have many potential uses in the prevention or treatment of various diseases. Flaxseeds have been classified as functional food because it provides numerous health benefits in addition to serving as a source of nutrients.No doubt flaxseeds are beneficial in several ways but their consumption in excess amounts may result in some side effects such as allergies, oxidation/rancidity, increase in bleeding and bleeding time, elevation of blood sugar levels, deficiency of ω-6 fatty acids and psychological problems. They have also been considered as a good mood food.
... Magnesiumexerts its effect by relaxing the nervous system and muscles and overcoming the night terrors (Jyotsna, 2012). • Anti-cancerous properties:After consuming flaxseeds, secoisolariciresinol (SDG) present gets converted into active mammalian lignansenterodiolaandentero-lactone, which have the potential to reduce the growth of cancerous tumors, especially hormone-sensitive ones such as those of the cancers of breast (Brzezinski & Debi, 1998;Bruno, 2009), endometrium and prostate (Tour´e & Xueming, 2010).Lignans have an antioxidant activity and contributed to the anti-cancerous activity of flaxseed Kitts, Yuan, Wijewickrame, & Thompson, 1999;Yuan, Richard, & Thompson, 1999;Kangas, Saarinen, & Mutanen, 2002). Lignan, enterodiol and enterolactone are believed to be responsible for inhibiting the growth of human prostate cancerous cells (Lin, Awitzer, & Demark-Wahnefried, 2001). ...
... Prasad, 2005 [56] suggested that lignan may act to prevent oxygen radical production, thus effectively reducing atherosclerosis. Lignans have antioxidant activity and thus may contribute to the anticancer activity of flaxseed [57,58]. Although in one clinical trial, flax-derived SDG/ lignan complex did not affect blood lipids [44] whereas studies in rabbits found a lipid-lowering effect of a flax SDG/lignan complex. ...
... Prasad, 2005 [56] suggested that lignan may act to prevent oxygen radical production, thus effectively reducing atherosclerosis. Lignans have antioxidant activity and thus may contribute to the anticancer activity of flaxseed [57,58]. Although in one clinical trial, flax-derived SDG/ lignan complex did not affect blood lipids [44] whereas studies in rabbits found a lipid-lowering effect of a flax SDG/lignan complex. ...
... SDG ranges from 11.7 to 24.1 mg/g in defatted flour and 6.1 to 13.3 mg/g in whole flaxseed flour (Johnsson et al., 2000). Lignans have antioxidant activity and thus may contribute to the anticancer activity of flaxseed (Yuan et al., 1999;Kangas et al., 2002;Prassad 1997). However, number of factors may contribute to the various anticancer activity of flaxseed (Thompson et al., 2005). ...
Flaxseed is cultivated in many parts of world for fiber, oil as well as for medicinal purposes and also as nutritional product. It is a native of Egypt but also cultivated in India, Holland, Russia and Britannia mainly for the purpose of its oil and fiber and is best adapted to fertile, fine textured, clay soils. Flax was valued in Ancient and Early Modern times as both a food and medicine. In this review, nutrients, anti-nutrients, functional properties and health benefits of bioactive molecules viz., essential fatty acids, lignans and dietary fiber of flaxseed are discussed. Flaxseed contains good amount of á-Linolenic Acid (ALA), omega-3 fatty acid, protein, dietary fiber, lignan specifically Secoisolariciresinol diglucoside (SDG). ALA is beneficial for infant brain development, reducing blood lipids and cardiovascular diseases. Researchers reported that flaxseed incorporated food products can have good consumer acceptability along with its nutritional benefits.
... Substance Bioactivity 2008), inhibition of platelet aggregation ( Rogers et al., 2000), inhibition of enzyme activity ( Funke and Melzig, 2005) 208. 20268-71-7 Hydroxymatairesinol Cytotoxic ( Kawahara et al., 2010), antioxidant, antitumor ( Kangas et al., 2002) 209. 32208-45-0 Methyl ursolate Cytotoxic ( Mallavadhani et al., 2012), antiprileferative ( Leal et al., 2012), antiviral ( Ren et al., 2012), antineoplastic, antiinflammatory ( Banno et al., 2005) 210. ...
Softwood bark is an important source for producing chemicals and materials as well as bioenergy. Extraction is regarded as a key technology for obtaining chemicals in general, and valorizing bark as a source of such chemicals in particular. In this paper, properties of 237 compounds identified in various studies dealing with extraction of softwood bark were described. Finally, some challenges and perspectives on the production of chemicals from bark are discussed.
This paper reviews the current status and summarizes the wide-ranging activities of variously functionalized bark-substances. They represent very important substances that play a major role in naturally occurring products. There has been an increasing interest in the use of bark extractives and class of bioactive substances, that also shows cytotoxic (properties of 25 identified substances), antioxidant (26 substances), fungicidal (20 substances), antibacterial (42 substances), anti-inflammatory (22 substances), antiviral (9 substances), antitumor (12 substances), antimalarial (6 substances), insecticidal (10 substances), antimutagenic (5 substances), pharmacokinetic (5 substances), pheromone activities (10 substances), inhibition of different activities (50 substances) and other properties. Compounds in extracts: (-)-Isolongifolol, methyl ether; (+)-hedychilactone; (2E)-5-(7a-Isopropenyl-4,5-dimethyloctahydro-1H-inden-4-yl)-3-methyl-2-pentenal; (9Z)-9-Tetradecenal; (E)-Nerolidol; (E)-β-Farnesene; (E)-β-Ionone; (E)-γ-Bisabolene; (R)-carvone; (Z)-α-bisabolene; (Z)-β-Farnesene; (Z)-γ-Bisabolene; 1,3,8-p-Menthatriene; 1,5-Cyclodecadiene; 1,7-di-epi-α-Cedrene; 1,8-Cineole; 13,16-Docosadienoic acid; 13-epi-manoyl oxide; 14-hydroxy-α-Muurolene; 15-Hydroxy-7-oxodehydroabietic acid, methyl ester; 15-Methoxydehydro-abietic acid, methyl ester; 1-epi-Cubenol; 1-Nonadecanol; 2,8,8-Trimethyl-4-methylene-2-vinylbicyclo[5.2.0]nonane; 3,4-Dimethoxytoluene; 3,5-dimethoxytoluene; 3-Carene; 3-n-Heptyl-7-methyl-9-(2,6,6-trimethylcyclohex-1- enyl)nona-2,4,6,8-tetraenal; 3-Vinylcycloocten; 4'-Ethyl-4-pentyl-1,1'-bi(cyclohexan)-3-ene; 7-Isopropyl-4a-methyloctahydro-2(1H)-naphthalenone; 7-Oxodehydroabietic acid, methyl ester; 9-Hexacosene; Abieta-7,13-diene; Abieta-8,11,13-triene; agathadiol; Alloaromadendrene oxide-(1); ar-Cucumene; Astringin; Benzaldehyde; Borneol; Bornyl acetate; Butyl 6,9,12-hexadecatrienoate; Cadalene; Cadina-1,4-diene; Campesterol; Camphene; Camphene hydrate; Camphor; Caparratriene; Caryophyllene oxide; Catechin; Cembrene ; cis-Abienol; cis-communic acid; cis-Muurola-4(14),5-diene; cis-Sabinene hydrate; cis-Verbenol; Citronellol; Cubenene; Cubenol; Cyclododecyne; Cyclosativene; Decanal; dehydroabietic acid; Dimethyl azelaate; Dimethyl docosanedioate; Dimethyl henicosanedioate; Dimethyl hexadecanedioate; Dimethyl icosanedioate; Dimethyl octadecanedioate; docosane; docosanol; ehletianol C; Eicosane; Ellagic acid; Epicatechin; epi-Cubebol; Ethyl oleate; Ferulic acid; Fumaropimaric acid; Gallic acid; Germacrene B; Germacrene D; Germacrene D-4-ol; Gleenol; guaiazulene; Heneicosane; Hentriacontane; Hexadecanoic acid; Hexanal; Hydroxymatairesinol; Isocaryophyllene; isolariciresinol; isolongifolol; Isopimaric acid; Isopropyl heptadecanoate; Isopropyl hexadecanoate; Isorhapontigenin; Isorhapontin, Isosteviol methyl ester; Kauren-18-ol, acetate, (4.beta.)-; lariciresinol; Lariciresinol-9-p-coumarate; Limonene; Longiborneol; Longicyclene; longifolene; Maleopimaric acid; Manool; Manoyl oxide; Margaric acid methyl ester; Mayurone; Mercusic acid; Methyl (6E,9E,12E,15E)-6,9,12,15-docosatetraenoate; Methyl (9E)-14-methyl-9-pentadecenoate; Methyl 10,13-dimethyltetradecanoate; Methyl 10-methyldodecanoate; Methyl 10-methyloctadecanoate; Methyl 11-methyloctadecanoate; Methyl 12-methyltetradecanoate; Methyl 13-methyltetradecanoate; Methyl 14-methylhexadecanoate; methyl 15-hydroxy-7-oxoabieta-8,11,13-triene-18-oate; Methyl 15-hydroxydehydro-abietate; Methyl 15-methylpalmitate; Methyl 18-methylnona-decanoate; Methyl 20-methyldocosanoate; Methyl 3,4-dimethoxybenzoate; Methyl 8-methyldecanoate; Methyl abieta-8,13(15)-dien-18-oate; Methyl abietate (Abalyn); Methyl beheniate; Methyl dehydroabietate; Methyl isopimarate; Methyl levopimarate; Methyl lignocerate; Methyl myristate; Methyl oleate; Methyl palmitate; methyl palmitoleate; Methyl pentadecanoate; Methyl pimara-8(14),15-dien-18-oate; Methyl pimarate; Methyl sandaracopimarate; Methyl stearate; Methyl ursolate; Methyl vaccenate; Methylcarvacrol; Methylthymol; Myrcene; Neoabietic acid; Neocembrene; Nonadecane; Nonanal; octadecane; Oleic acid; Oplopanone; Palustradiene; Palustric acid; p-Coumaric acid; p-Cymene; Pentacosylic acid; Pentadecane; Pentadecanoic acid; Piceatannol; Piceid; Pimaradiene; Pimaral; Pinocamphone; Pinolenic acid methyl ester; Podocarpic acid; Quercetin; Resveratrol; Retinol, acetate; Sabinene; Santene; Sativene; Sclareol; sesquipinsapol B; Sinapic acid; Stearyl acetate; Stigmastan-3,5-diene; Syringic acid; Tannic acid; Taxifolin; Terpinen-4-ol; Terpinolene; Thuja-2,4(10)-diene; Thunbergol; trans-α-Bergamotene; Tricyclene; Valencene; Vanillic acid; Verbenone; vladinol D; Z-β-Ocimine; α-Bisabolene; α-Bisabolol; α-Cadinene; α-cadinol; α-Calacorene; α-Campholene aldehyde; α-Cedrene; α-Copaene; α-Cubebene; α-Fenchene; α-Humulene; α-Longipinene; α-muurolene; α-neo-Clovene; α-Phellandrene; α-Pinene; α-Selinene; α-Terpinene; α-Terpineol; α-Thujene; α-Ylangene; β-Calacorene; β-Cedrene; β-Curcumene; β-Fenchol; β-Gurjunene; β-Longipinene; β-neoclovene; β-Phellandrene; β-Pinene; β-sitosterol acetate; γ-cadinene; γ-Curcumene; γ-muurolene; γ-Terpinene; δ-13-(trans)-Neoabienol; δ-cadinene; τ-cadinol; τ-muurolol.
Highlights
This review highlights the substances that are associated with the softwood bark and have beneficial properties.
Individual compounds show antioxidant, fungicidal, antibacterial, antimycotical, antiinflammatory, cytotoxic, antiviral, antitumor, antimalarial, insecticidal, antimutagenic, inhibition of different activities and other applicable properties.
In total 237 compounds were characterized by properties from the literature and by computating of ADME properties.
Application of pheromone compounds found in spruce tree bark in the protection of damaged forest stands.
Contents
1. Bark – an introduction
1.1. Bark in nature
1.2. Compositions of softwood bark
2. Extraction and extractive compounds
2.1. Extraction techniques and their achievements
2.2. Extractive compounds and their properties
3. Structure-activity studies on extracted compounds
3.1. Structure-activities modes
3.2. ADME-related properties prediction
4. Outlook for future
5. Conclusion
... & Francis Colin fcolin@inra.fr supplements (Kangas et al. 2002;Cosentino et al. 2007;Välimaa et al. 2007;Phelan et al. 2009;Loers et al. 2014;Spilioti et al. 2014;Yatkin et al. 2014;Laavola et al. 2015). The biological reasons of this chemical richness have not been definitely elucidated, and several suggestions exist for explaining it, but none has been firmly verified to date. ...
The physiological and ecological mechanisms
controlling the knot richness in extractives require further
investigations. We aim to design a model of the vertical
distribution of the knot extractive concentrations as a prerequisite
for further studies on the eco-physiological studies.
At a first attempt, we use this model to test the effect of
different competition situations. Fifteen Silver fir trees
were sampled according to their social status within three
thinning treatments. Discs containing knots were sampled
according to their position in reference to the lowest living
branch of each tree. Extractions were carried out with
hexane and acetone successively. Extractive concentrations
in both solvents as well as branch diameters were simultaneously
modelled through the seemingly unrelated
regression method. For all trees, knot extractive concentrations
increase from the tree tip to the living crown base.
According to the model, trees with the longest crowns,
dominant or/and growing in the thinned stands, exhibited
the largest knot extractive concentrations. The model
depicted a vertical trend that strongly suggested inducing
physiological factors such as protection zone, branch
heartwood formation combined with compression wood
formation. A strategy was proposed for the quantification
of the effect of the ecological factors on the extractive
concentrations of knots when these factors act either
directly or indirectly via physiological factors. The model
is thus an efficient tool to quantify the eco-physiological
control on knot extractives.
... Lignans were also found in large amounts (6-24% w/w) in Finnish spruce knots. The 7-hydroxy derivative of matairesinol, hydroxymatairesinol, is the major lignan found in heartwood and in particularly high concentrations in knotwood of Norway spruce Picea abies, amounting to 65-85% of all identified lignans [196], A food supplement has been developed in Finland on the basis of hydroxymatairesinol from Norway spruce under the trade name HMRlignan™ [197], A study on lignans and stilbenes from Norway spruce (Picea abies) and pine from central Norway has confirmed the same principal lignan constituents as determined in a Finnish study [198], Hydroxymatairesinol has been determined to constitute over 84% of all lignans in Picea abies knotwood, which contained 10-fold higher concentrations of lignans than the surrounding heartwood. Hydroxymatairesinol has been used as a chiral source in the synthesis of derivatives with bioactive effects. ...
An overview of chemical properties of wood constituents is presented in this chapter. The structural wood components, polysaccharides (cellulose and hemicelluloses) and lignins, are presented first, offering some comparisons of chemistry between normal and reaction woods (compression and tension). Knowledge about the chemistry of basic polymers of wood and other lignocellulosic resources is indispensable for understanding the processes involved in their transformation. The emergence of biorefinery concept is related to the need of complete utilization of lignocelulosic resources. The properties of industrial lignins issued from the major pulping processes are presented and related both to the process features and to their innovative applications. The most important classes of extraneous wood components (terpenoids and polyphenols) are presented. Their availability from forest biorefineries is described in relation to potential applications in the nutraceutical, cosmetic and pharmaceutical sectors.
... It is interesting that Norway spruce (Picea abies) contains up to 6-29% lignans by mass, with the most abundant lignan being hydroxymatairesinol (HMR), which accounts for 70-85% of the total lignan content. Kangas et al. (2002) presented a paper on the antioxidant and antitumor effects of HMR. This is very important information and provides the basis for food enrichment with lignans. ...
Hydroxymatairesinol (HMR) is the main lignan found in spruce knots. This lignan has been used for enrichment of musts and wines. Quality parameters of these products have been studied for several years and for storage times up to one year. Parameters included HMR concentration, antioxidant activities expressed as ferric reducing antioxidant power and 2,2-difenyl-1-picrylhydrazyl, total polyphenols, and sensory parameters, i.e. consumer acceptability. The main goal of this work was to study and provide relationships between the above mentioned quality parameters. We analysed cross-correlations of all these parameters and found statistically significant correlations between lignan concentration and consumer acceptability, which can be phrased as a warning against high lignan concentrations. The strongest correlations were found between antioxidant parameters and total polyphenol content that supports the antioxidative behaviour. © 2016, Czech Academy of Agricultural Sciences. All rights reserved.
... The most often explored bioactive substances from wood are terpenes and lignans (DOMINGUES et al., 2011;HOLMBOM et al., 2003). These substances are supposed to provide health effects, such as antioxidant potential, supporting weight loss, active agent against osteoporosis and positive cardiovascular effects (LI et al., 2010;SARAVANAN and PUGALENDI, 2006;KANGAS et al., 2002;KREIJKAMP-KASPERS et al., 2004;KIM et al., 2002). The techno-economic feasibility of newly developed production processes is often assessed by analysing the calculated production costs through a system-analysis-approach. ...
Plant-based food additives in functional foods can improve consumer’s nutrient uptake and promote optimal health effects. Considering the ongoing development of new technologies for extracting bioactive substances the potential pricing of these substances plays a major role in assessing the overall profitability of new technologies. The study therefore assessed potential prices for not yet commercially existing bioactive substances from wood by carrying out a business-to-businesssurvey. Applying the van Westendorp method the study identified a potential price in context of varying product properties like different health claims or increasing purities. The Indifference Price of 101.5 €/kg can be considered as a guide value to assess the overall profitability. The study identified potential price ranges for such products and provided information that can be used for according pricing strategies. © 2014, OGA-Osterreichische Gesellschaft fur Agrarokonomie. All rights reserved.
... Recent report of anti-viral activity and its potential as a remedy for hepatitis B-virus infection has also attracted researchers to evaluate the potential of the plant (Martins et al., 2011). Lignans have shown anti-mitotic, anti-tumor, anti-viral (MacRae and Towers, 1984) anti-HIV (Schroder et al., 1989) activities and protective effects against hormone-related cancers due to their antioxidant effects (Kangas et al., 2002;Lee and Xiao, 2003;Saarinen et al., 2000). Phyllanthin are the main characteristic lignans of the plant which have shown estrogenic properties, reduces toxicity, vascular tension, and protect hepatocytes (Chirdchupunseree and Pramyothin, 2010;Inchoo et al., 2011;Islam et al., 2008). ...
... Present decade-, natural products have renewed vested interest in investigating led to the advent of several important anticancer substances such as vinblastine, vincristine, paclitaxel, and the semi-synthetic drugs Etoposide, Etopophos and Teniposide. The latter three compounds are chemical derivatives of podophyllotoxin, which belongs to the lignan group of compounds; possess remarkable therapeutic potential including antitumor, anti-inflammatory, immunosuppressive, cardiovascular, antioxidant and antiviral actions [4][5][6][7][8][9][10][11]. ...
... Furthermore, flaxseed dietary fibers exhibit positive effects of reducing constipation (Ganorkar & Jain, 2013). SDG have been proved for antioxidant activity and free oxygen radical scavenging activity (Kitts, Yuan, Wijewickreme, & Thompson, 1999) and has shown to possess anticancer properties (Kangas, Saarinen, & Mutanen, 2002). Several studies have revealed that flaxseed components can provide health benefits in human beings. ...
... Present decade-, natural products have renewed vested interest in investigating led to the advent of several important anticancer substances such as vinblastine, vincristine, paclitaxel, and the semi-synthetic drugs Etoposide, Etopophos and Teniposide. The latter three compounds are chemical derivatives of podophyllotoxin, which belongs to the lignan group of compounds; possess remarkable therapeutic potential including antitumor, anti-inflammatory, immunosuppressive, cardiovascular, antioxidant and antiviral actions [4][5][6][7][8][9][10][11]. ...
... Prasad (2005) suggested that lignan may act to prevent oxygen radical production, thus effectively reducing atherosclerosis. Lignans have antioxidant activity and thus may contribute to the anticancer activity of flaxseed Kangas et al., 2002;Prassad 1997). However, number of factors may contribute to the various anticancer activity of flaxseed ( Thompson et al., 2005). ...
Flaxseed is mainly considered as oilseed crop. Moreover, the other nutritional parameters than its oil content, make it more favorable choice for food technologist to develop functional foods. Flaxseed contains good amount of α-Linolenic Acid (ALA), a omega-3 fatty acid, protein, dietary fiber, lignan, specifically Secoisolariciresinol diglucoside (SDG). Several studies reveal that these components work well for nutritional benefit in human being. ALA is beneficial for infant brain development, reducing blood lipids and cardiovascular diseases. Flaxseed proteins are relatively high in arginine, aspartic acid and glutamic acid whereas lysine, methionine and cystine are limiting amino acid. Flaxseed dietary fiber exhibits positive effect to reduce constipation, to keep better bowel movement and as hypocholestermic agent. SDG have antioxidant activity and free oxygen radical scavenging activity. Consequently, it may have anticancer property. At some extent, SDG helps in bone development. Cyanogenic glycosides and linatine are antinutrients in flaxseed. As compared to soyabean and canola, flaxseed antinutrient effect on human health is very less. Researchers reported that flaxseed incorporated food products can have good consumer acceptability along with its nutritional benefits.
... In laboratory models of uterine, breast, colon, and other carcinomas, HMR lignan has demonstrated efficacy in reducing the volume and growth of existing tumors and preventing the formation of new tumors. 22,[25][26][27][28][29] Bioavailability-that is, the ease with which HMR lignan is converted directly to enterolactone and absorbed into the bloodstream-is what sets HMR apart from other plant lignans. Its unique chemical composition allows natural gut bacteria to convert HMR directly to the beneficial enterolactone and enterodiol lignans. ...
... Several additional mechanisms for lignan action in carcinogenesis have been suggested such as inhibition of 5α-reductase activity [52] and transactivation through human androgen receptor [53]. Many dietary plant lignans as well as enterolignans possess potent antioxidative activity in vitro545556 that may have significance in elimination of DNA damages caused by oxygen and nitrogen radicals. It is known that sesame seed lignans elevate blood tocopherol concentrations [57] suggesting one putative mechanism of dietary lignans in prostate carcinogenesis. ...
Lignans and their in vivo metabolites, especially enterolactone (ENL), have attracted substantial interest as potential chemopreventive agents for prostate cancer. Preclinical and clinical interventions performed with lignan-rich flaxseed that use surrogate biomarkers as endpoints suggest that lignans may attenuate prostate carcinogenesis in individuals with increased risk or with diagnosed cancer. No unequivocal prostate cancer risk reduction has been found for lignans in epidemiological studies, suggesting that lignan concentrations found in populations consuming a regular non-supplemented diet are not chemopreventive in prostate cancer. Presumably, the main obstacles in assessing the efficacy of food lignans is limited knowledge of the serum and tissue lignan concentrations required for the putative prevention. Further clinical studies performed with the purified compounds are required to substantiate a health claim.
... 22 A lignan source derived from the Norwegian spruce tree, 7-hydroxymatairesinol (HMR lignan) had antitumor effects in rat mammary cancers, and positively influenced the concentration of 2-OHE and the ratio of 2-OHE : 16α-OHE1 in human clinical trials. 23,24 The purpose of this study was to determine the effects of supplementation the diets of women (not taking hormonal supplements or oral contraceptives) with an encapsulated combination of I3C and HMR lignan on urinary concentrations of 2-OHE and 16αOHE, on the ratio of 2-OHE to 16α-OHE, and on concentrations of serum enterolactone. ...
Both indole-3-carbinol and dietary lignans have beneficial effects on estrogen metabolism and breast cancer risk. There is no published literature on the effects of a combination product. This study was designed to investigate the impact of a combination product on estrogen metabolism. The major trial objective was to determine whether a breast health supplement containing indole-3-carbinol and hydroxymatairesinol lignan would alter estrogen metabolism to favour C-2 hydroxylation and reduce C-16 hydroxylation. Higher concentrations of C-2 metabolites and lower concentrations of C-16 metabolites may reduce breast cancer risk and risk for other hormonally-related cancers.
Forty-seven pre-menopausal and forty-nine post-menopausal women were recruited for this study, and were divided by random allocation into treatment and placebo group. The treatment supplement contained HMR lignan, indole-3-carbinol, calcium glucarate, milk thistle, Schisandra chinesis and stinging nettle, and each woman consumed either treatment or placebo for 28 days. At day 0 and day 28, blood samples were analysed for serum enterolactone concentrations, and first morning random urine samples were assessed for estrogen metabolites. Repeated measures ANOVA statistical testing was performed.
In pre-menopausal women, treatment supplementation resulted in a significant increase (P < 0.05) in urinary 2-OHE concentrations and in the 2:16α-OHE ratio. In post-menopausal women, treatment supplementation resulted in a significant increase in urinary 2-OHE concentrations. In pre- and post-menopausal women combined, treatment supplementation produced a significant increase in urinary 2-OHE concentration and a trend (P = 0.074) toward an increased 2:16α-OHE ratio. There were no significant increases in serum enterolactone concentrations in the treatment or placebo groups.
Supplementation with a mixture of indole-3-carbinol and HMR lignan in women significantly increased estrogen C-2 hydroxylation. This may constitute a mechanism for the reduction of breast cancer risk as well as risk for other estrogen-related cancers. Further studies with higher numbers of subjects are indicated.
Plant-derived phenolic compounds are recognized to provide several health benefits for humans, including anticancer, anti-inflammatory, and antioxidant proprieties. Their bioavailability in the human body has a significant impact on these outcomes. Their bioaccessibility and bioavailability are highly dependent on the structure and manner in which phenolics enter into the organism, through a complex food matrix, for instance, or as pure isolates. Furthermore, the bioaccessibility of phenolic compounds in the body is greatly impacted by interactions with a broad range of other macromolecules (such as proteins, lipids, dietary fibers, and polysaccharides) in food or during digestion. Encapsulation is a process that can improve bioaccessibility and bioavailability by guaranteeing coating of the active ingredients, controlled release, and targeted distribution to specific parts of the digestive system. However, this field has not yet received enough attention, due to the complex mechanisms through which phenolics act in the body. This review attempts to shed light on the results of research that has been performed on the potential and therapeutic benefits of encapsulated polyphenols in both health and disease.
The genus Plumeria of the Apocynaceae family has a rich history of traditional medicines supported by empirical evidences. This review consolidates diverse biological attributes, phytochemical compositions, physical properties (melting point, shape, optical rotation, etc.), and analytical data (UV, IR, Mass spectroscopic data, elemental analysis) of various species of Plumeria. The review covered the chemistry of wide range of natural compounds like iridoids, triterpenoids, alkaloids, flavonoids, steroids, cardiac glycosides, quinones, anthocyanins, cardenolides, fatty acid esters, lignans, coumarins, etc. found in various species of the genus Plumeria. Analytical techniques including chromatography, IR, UV, and mass spectroscopy have significantly contributed to elucidating the complex chemical profiles of extracts of various species of Plumeria which are systematically presented in a tabular format. The review also defines the historical background, geographical distribution, and traditional uses of various species of the genus Plumeria. The review also includes the mechanisms of action and biotransformation of compounds, providing a deeper understanding of their therapeutic potential. The comprehensive review reveals the significance of the natural products isolated from a number of species of genus Plumeria. It is also suggestive that there is an extensive scope for further investigation to explore new therapeutic components of the genus Plumeria.
7-hydroxymatairesinol (7(OH)MR) is the main lignan of spruce extracts, characterized by oncoprotective and anti-inflammatory properties. The results of chemoreactome modeling made it possible to formulate the molecular mechanisms of the pharmacological effects of 7(OH)MR for anti-inflammatory (inhibition of 5-lipoxygenase, matrix metalloproteinase MMP2, mitogen-activated kinase p38-alpha, leukotriene b4 receptor, prostacyclin receptor), oncoprotective (antioxidant effect due to inhibition heme oxygenase-2, inhibition of cyclin-dependent kinases 3 and 4, epidermal growth factor, mTOR protein). An assessment of the transcriptomic effects of 7(OH)MR in breast cancer cells showed significant dose-dependent effects on the transcription of 3468 of 12700 genes. The 7(OH)MR molecule, reducing the expression of proliferative genes (401 genes) and chronic inflammation (148 genes), while simultaneously increasing the transcription of oncoprotective immunity genes (100 genes), inhibits the proliferation of tumor cells. Experiments on solid Ehrlich carcinoma showed a significant oncoprotective effect of 7(OH)MR at doses of 60, 120 mg/day, even while taking estrogen ( p = 0.007). A clinical study showed that 7(OH)MR (60 mg/day, 1 month) helps normalize estrogen metabolism and improve the clinical symptoms of mastopathy.
Lignans are known to exhibit a broad spectrum of biological activities, indicating their potential as constituents of feed supplements. This study investigated two extracts derived from the feed supplements ‘ROI’ and ‘Protect’—which contain the wood lignans magnolol and honokiol (‘ROI’), or soluble tannins additional to the aforementioned lignans (‘Protect’)—and their impact on selected parameters of intestinal functionality. The antioxidant and anti-inflammatory properties of the extracts were determined by measuring their effects on reactive oxygen species (ROS) and pro-inflammatory cytokine production in vitro. The impact on intestinal barrier integrity was evaluated in Caco-2 cells and Drosophila melanogaster by examining leaky gut formation. Furthermore, a feeding trial using infected piglets was conducted to study the impact on the levels of superoxide dismutase, glutathione and lipid peroxidation. The Protect extract lowered ROS production in Caco-2 cells and reversed the stress-induced weakening of barrier integrity. The ROI extract inhibited the expression or secretion of interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). Moreover, the ROI extract decreased leaky gut formation and mortality rates in Drosophila melanogaster. Dietary supplementation with Protect improved the antioxidant status and barrier integrity of the intestines of infected piglets. In conclusion, wood lignan-enriched feed supplements are valuable tools that support intestinal health by exerting antioxidant, anti-inflammatory and barrier-strengthening effects.
The present work consists of the development of a methodology based on reverse-phase frontal chromatography to separate and purify different fractions of wood extract. Equilibrium isotherms of each compound were first determined for 9 ethanol: water concentrations. A model was developed to simulate the profiles obtained by frontal chromatography. The fitting of simulated and experimental profiles led to the validation of the model and to the fact that the studied compounds present linear isotherms even in high concentration ranges. Simulation can therefore be carried out to optimize separations performances. Three purification strategies were considered: (a) separation of the two major classes of families, (b) separation of both Hydroxymatairesinol isomers, and (c) separation of each isomer. The simulation showed a high dependency on ethanol concentration and the best condition for optimizing the load volume was at the lower ethanol concentration (3 v.v.%). For a 250 × 4.6 mm analytical column, the simulation showed that volumes of 6021.0 mL (a), 450.2 mL (b) and 127.9 mL (c) could be loaded. Scale-up criteria are then briefly discussed for large-scale production.
Lignans are naturally-occurring compounds produced and accumulated in several edible and medicinal plants, which can be subdivided biosynthetically into lignans and neolignans. Once consumed, they can be transformed by gut microbiota into bioactive mammalian lignans. Such is the case of the conversion of the most studied and known dietary lignan, secoisolariciresinol diglucoside (SDG), into enterolactone (ENL) and enterodiol (END). Updated results comprising the action of these lignans (even other (neo)lignans) suggest that they exhibited positive effects on different diseases/disorders due to their free radical scavenging activity or capacity and capability to coordinate divalent transition metal ions to form complexes, in spite of a plausible, partially-registered prooxidant action. Therefore, some (neo)lignans are described as favorable chemical entities to human health, which their safety is also suitable since no detrimental effects are reported for the intake of some dietary lignans, exhibiting a more preventive than curative effect on diseases. Hence, in order to cover such an information about dietary (neo)lignans and their potential on human health as antioxidants, this document gathers the available information from chemical and biological point-of-views, including several topics such as sources, chemistry, bioavailability, antioxidant activity and action mechanisms, beneficial effects, and in vitro and animal/clinical studies.
The present study investigates the chemical properties and sensory attributes of beef sausages which have been incorporated with three tomato powder levels (0, 1.5 and 3%) and three flaxseed powder levels (0, 3 and 6%). All samples were stored at 4 °C for 42 days. The addition of tomato and flaxseed powders decreased (P < .001) L* values, pH, residual nitrite and moisture contents and increased b* value (P < .001), protein, carbohydrate, ash, fiber and total calories contents. The nitrite content decreased during the storage time. Linolenic acid increased with the addition of flaxseed powder. Generally, adding tomato and flaxseed powders up to 3% had no effect (P > .05) on the sensory evaluation parameters on cooked and fried sausages. Based on the obtained results, it is possible to produce sausages incorporated with tomato and flaxseed powders and introduce to the market as a new processed meat product.
Objectives Investigation the cytogenetic activity and antioxidant role of methanolic extract of flaxseeds in male albino rats treated with cyproterone acetate. Methods The first part contains a phytochemical analysis of flaxseeds 20% methanolic extract include: Thin layer chromatography (TLC), determination of active compounds, and antioxidant activity of flaxseeds extract. The second part was experimental groups include 35 rats divided randomly into 7 groups: first and second groups treated with distilled water (D.W) and corn oil respectively as control groups, cyproterone acetate (CPA) (10 mg/kg/day) group, flaxseeds extract (250 and 500 mg/kg/day) respectively, and groups treated both CPA with flaxseeds extract with the same doses above respectively. After 50 days, the cytogenetic study including mitotic index (MI) and chromosomal aberrations (CA) of bone marrow cells in addition to the levels of DNA fragmentation in both white blood cells (WBC) and testes tissues was assessed. Results Presence of some phytochemical and antioxidant compounds in 20% methanolic extract of flaxseeds. CPA group had a significant increase (P≤0.05) in MI and CA compared to both D.W and corn oil control groups and has a high level of DNA fragmentation in both WBC and testes tissue. In contrast, flaxseeds extract alone or with CPA did not induce a significant difference in MI and CA but it considered as significant decreasing (P≤0.05) when compared with CPA group. Furthermore, both groups treated with flaxseeds 250 and 500 mg/kg/day alone did not record any fragmentation of DNA of WBC but caused fragmentation of DNA of testes tissue. While a decreased level of DNA fragmentation of WBC and testes tissue was noted in CPA with flaxseeds treated groups when compared with the CPA group. Conclusions The methanolic extract of flaxseeds had a cytogenetic activity to suppresses mitogenic and genotoxic effects of CPA via its antioxidant properties.
Les sous-produits qui proviennent de l’industrie du bois, particulièrement les nœuds, contiennent différents types de molécules qui peuvent être valorisées comme source de composants bioactifs pouvant répondre à des besoins thérapeutiques. C’est sur cette idée que le projet "Le Bois Santé" a été conçu. Grâce à la collaboration de plusieurs partenaires, le présent travail vise dans un premier temps à développer des procédés d’extraction "verts" (solide-liquide et supercritique) pour obtenir un extrait riche en lignanes à partir d’un mélange de nœuds d’épicéa commun et de sapin pectiné. Les effets des conditions opératoires sur le rendement d’extraction de chaque composé cible et sur l’activité anti-oxydante des extraits ont été déterminés. Afin d’étudier le procédé complet, le projet vise à étudier l’impact des procédés de concentration et de séchage de l’extrait à partir de l’évaporation sous vide et de la lyophilisation. De plus, la séparation et la purification des composés ont été développées et optimisées par simulation grâce à la technique de chromatographie frontale
Lignans are secondary metabolites synthesized by plants and exhibit a wide range of remarkable biological activities. In this chapter, the biosynthesis, metabolism, and the role of lignans in plant defense are extensively treated. All these details have been developed according to structures of main families and types in order to signify, when possible, the relationship between structures and biological activities . A special attention has been paid to podophyllotoxin and related substances due to their remarkable antitumoral properties.
Replacement of wheat flour with varying levels of flaxseed flour (0–30%) on nutritional, functional and antioxidant properties of cookies was investigated. Cookies produced from composite flour mixes were significantly (p<0.05) higher in protein, fat, ash and fiber contents than the control. Flaxseed was found to be rich in antioxidant potential as evident from the higher total phenolic content, free radical scavenging activity and reducing power of composite flour cookies in comparison to control. The results indicated that as the concentration of flaxseed flour in the blend increased, the cookies became darker in color with a significant (p<0.05) increase in their spread factor. Sensory panellists rated cookies containing 15% level of flaxseed flour as highly acceptable in relation to their overall acceptability scores. Beyond this level of replacement the texture and flavour of cookies was adversely affected. Principal component analysis revealed that physicochemical and sensory properties of cookies produced by 10% replacement with flaxseed flour were closest to the control cookies.
Antioxidant compounds play a vital role in human physiology. They prevent the oxidation of biomolecules by scavenging free radicals produced during physiochemical processes and/or as a result of several pathological states. A balance between the reactive oxygen species (free radicals) and antioxidants is essential for proper physiological conditions. Excessive free radicals cause oxidative stress which can lead to several human diseases. Therefore synthesis of the effective antioxidants is crucial in managing the oxidative stress. Biotransformation has evolved as an effective technique for the production of structurally diverse molecules with a wide range of biological activities. This methodology surpasses the conventional chemical synthesis due to the fact that enzymes, being specific in nature, catalyze reactions affording products with excellent regio- and stereoselectivities. Structural transformation of various classes of compounds such as alkaloids, steroids, flavonoids, terpenes have been carried out through this technique. Several bioactive molecules especially those having antioxidant potential were also synthesized by using different biotransformation techniques and enzymes. Hydroxylated, glycosylated, and acylated derivatives of phenols, flavonoids, cinnamates, and other molecules have proven abilities as potential antioxidants.
Plant lignans are natural products resulting from the phenylpropanoid metabolic pathway. Lignans are of considerable interest in the treatment of cancer and other diseases. After a survey on plants containing lignan, Jatropha Gossypifolia (J.G) with lignan Arylnaphthalene was selected, which showed structural similarity with synthesized lignan (1-phenylnaphthalene). Plant Jatropha Gossypifolia has potent anticancer activity, have already been proved by various researchers. In a follow-up study, the lignans synthesized in our laboratory were also tested for its invitro cytotoxic activity using MTT assay. The results were found to be significant. A simple, rapid and specific method for the analysis of structurally similar lignan in the plant Jatropha Gossypifolia with synthetic organic compound (1-phenylnaphthalene) by a sensitive High Performance Liquid Chromatography technique is developed. The lignan peak was separated from endogenous peaks on phenomenex ODS 5μ C18 column (250 x 4.6mm) with mobile phase comprising of phosphate buffer: acetonitrile (70:30), pH-2 at a flow rate of 1ml/min and Ultra Violet detector at 230nm. Lignan 1-phenylnaphthalene was eluted at 4.047 minute and lignan from plant J.G was eluted at 4.077 minute.
Seeds from fruits such as Citrullus (C.) lanatus (watermelon) and Limonia (L.) acidissima (wood apple) are not commonly utilized but could be suitable in numerous food formulations. It was shown that the protein content of defatted seed flours was 71.38 and 49.51 % and that these contained considerable amounts of minerals such as Na, Mn, Mg, K, Cu, Fe and Zn. The defatted L. acidissima seed flour was superior to C. lanatus in essential amino acids. The flours obtained from both seeds were also evaluated for functional properties and characterized by X-ray diffraction, differential scanning calorimeter and scanning electron microscope (SEM). Amorphous nature was observed in defatted C. lanatus and L. acidissima flours due to the low percentage of degree of crystallinity. Spherical morphologies were observed through SEM. The exothermic peak was recorded in defatted C. lanatus and L. acidissima flour.
Flax seed (Linum usitatissimum) is popularly known as Alsi, Jawas, Aksebija, etc. in Indian languages, is a blue flowering crop that produces small, flat seeds ranging in colour from golden yellow to reddish brown. Flaxseed contains good amount of α-Linolenic Acid (ALA), omega-3 fatty acid, protein, dietary fiber, lignan specifically Secoisolariciresinol diglucoside (SDG). ALA is beneficial for infant brain development, reducing blood lipids and cardiovascular diseases. Flaxseed proteins (10.5% to 31%) are relatively high in arginine, aspartic acid and glutamic acid whereas lysine, methionine and cystine are limiting amino acids. Flaxseed dietary fiber exhibits positive effect to reduce constipation, to keep better bowel movement and as hypocholestermic agent. Flax seed contains dietary fibres and omega-3 fatty acids in the form of ALA, which can help reduce the risk of cancer, particularly breast and colon, by blocking tumour formation. Flax seed is an emerging as one of the key source of phytochemicals in the functional food area. The use of flax seed in different food products will be beneficial to protecting against cancer, heart disease, diabetes and lowering cholesterol level.
Considering the potential of flaxseed as functional ingredient, roasted flaxseed flour (RFF) was incorporated by substituting refined wheat flour at 5%, 10%, 15%, 25% and 30% in cookies formulations. Thickness and diameter of cookies increased as flaxseed flour was increased. Addition of flaxseed restricted the spread of cookies. 15% flaxseed flour incorporated cookies were found to be well comparable with control in sensory evaluation. Hardness and fracturability of experimental cookies increased up to 15% flaxseed flour incorporation. Thereafter, both these attributes showed decline trend. Chemical composition showed that moisture, ash, fat and protein content increased in flaxseed flour cookies than control. Fiber content was nine times more in flaxseed flour cookies than the control. Alpha linolenic acid (ALA) content increased from 0.19% (control) to 4.76% in optimized cookies. An improvement in polyunsaturated to saturated fatty acid ratio was observed while ω-6 to ω-3 fatty acid found to be decreased to well below maximum recommended value.
In the present study, we evaluated the anti-inflammatory properties of several plant lignans most commonly distributed in foods. 7-Hydroxymatairesinol (HMR) and its major isomer 7-hydroxymatairesinol 2 (HMR2), lariciresinol, secoisolariciresinol, and pinoresinol, isolated from Norway spruce knots were examined.
We investigated the anti-inflammatory effects of lignans on tumor necrosis factor-α-treated human aortic endothelial cells by measuring the expression of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 by cell ELISA and the adhesion of U937 monocytes to activated endothelial cells using a cell adhesion assay. Among the lignans studied, HMR and HMR2 significantly reduced intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 levels as well as the adhesion of U937 to endothelial cells. To further characterize the molecular mechanisms involved in this regulation, the effect of HMR and HMR2 on nuclear factor-κB, SAPK/c-Jun NH2-terminal kinase and extracellular signal regulated kinase phosphorylation was assessed.
Our results demonstrated that the lignans HMR and HMR2, dominant in cereals such as in wheat, triticale, oat, barley, millet, corn bran, and in amaranth whole grain, exhibit strong anti-inflammatory properties in endothelial cells, at least in part, through attenuation of nuclear factor-κB and extracellular signal regulated kinase phosphorylation.
Lignans are compounds found in a variety of plant materials including flaxseed, pumpkin seed, sesame seed, soybean, broccoli, and some berries. The major lignan in flaxseed is called secoisolariciresinol diglucoside (SDG). Once ingested, SDG is converted in the colon into active mammalian lignans, enterodiol, and entero-lactone, which have shown promise in reducing growth of cancerous tumors, especially hormone-sensitive ones such as those of the breast, endometrium, and prostate. Known for their hydrogen-donating antioxidant activity as well as their ability to complex divalent transition metal cations, lignans are propitious to human health. The extraction methods vary from simple to complex depending on extraction, separation, fractionation, identification, and detection of the analytes. Flax lignan is also a source of useful biologically active components found in plant foods, such as phytochemicals, and it is considered a functional food. The safety issues in flaxseed are also briefly discussed.
In addition to their nutritive value, foods provide health benefits or have a role in disease prevention since they contain a wide range of phytochemicals which represent functional or bioactive components. These bioactive molecules present in foods are based on a variety of chemical structures, from carotenoids, through sterols and fatty acids, to different types of polyphenols. In this review, the polyphenols which are common constituents of vascular plants are explored. They are also common constituents of fruits and vegetables, teas and cocoas. The extractable polyphenols, obtainable by solvent extraction of the forest biomass, are of special interest as they are readily available form different types of forest and wood transformation residues. Flavonoids, cinnamic acid derivatives and proanthocyanidins, which share a part of their biosynthetic pathway with lignins, and therefore are associated with "woody" character of the plants, are reviewed along with some non-flavonoids important as food constituents such as stilbenes and hydrolysable tannins. The foods rich in these polyphenols are reviewed along with the forest sources of the same classes of molecules. The emphasis is put on residues of wood transformation such as bark and knotwood as these materials represent particularly rich resources for bioactive polyphenol classes. One of the most notorious bioactive properties of polyphenols is their antioxidant activity. The most important results on antioxidant capacity of forest trees extracts are presented and compared to those obtained for the extracts from healthy foods rich in polyphenols. These results are discussed also in relation to total phenol content of the studied extracts. Finally, the results on the application of selected types of polyphenols or extracts from forest biomass in prevention and/or treatment of diseases which are related to oxidative stress, cardiovascular disease, Alzheimer and cancer, are presented. It is clear from all discussed results, that the forest biomass in general and the residues of wood transformation in particular, represent the important natural resources of bioactive polyphenols. These residues have a real potential to be used as raw materials for the development of food supplements and/or functional foods which can enhance the animal and human health by disease prevention. They are also applicable for cosmetics and pharmaceutical products development, but their application in disease prevention remains more straightforward.
Lignans have been part of both diet and herbal medicines for centuries. It is only in the last half century that phytochemists have described the structures of the lignans. Pharmacologists have only become interested in the biological activity of lignans in the last few decades. Much of the early interest focused on podophyllotoxin type lignans and their derivatives. Recent literature has recorded very many new lignans or lignan derivatives with a diverse range of biological activities. In 1955, the isolation from flax seed and the structure of the lignan derivative secoisolariciresinol diglucoside (SDG) was reported. Possible biological activity of SDG, and the mammalian lignan metabolites, enterolactone and enterodiol, was initially reported about 20 years later. During the next 30 years, there has been extensive research on the biological effects of both flax seed and rye lignans since both are metabolized into the mammalian lignans. Research on the activity of lignans on breast, colon, prostate and thyroid cancer has generally shown beneficial effects although there are some studies with either no conclusive or negative effect. Lignans have been shown to have positive effects in lowering relative risk factors for heart disease. Use of flax seed or SDG has been shown to have positive effects in both lupus and polycystic kidney disease models. Studies of both type I and II diabetes models have reported positive results when using SDG. Flax seed has also been reported to be hepatoprotective. Reproductive effects have been observed with flax seed or SDG and have been found to be dose and time related. There are many possible mechanistic explanations for the observed bioactivities including involvement in hormonal metabolism or availability, angiogenesis, anti-oxidation and gene suppression.
Dietary intake of whole-grain foods is associated with a decreased risk of chronic diseases such as diabetes, obesity and heart disease. In addition to dietary fibre, various phytochemicals have been suggested to contribute to the health effects of whole grain products. This review focuses on phenolic compounds in rye (Secale cereale L.), which is one of the major bread grains in Europe. Data on phenolic concentrations in rye grain and foods, their bioavailability to tissues and effects in vivo, and their potential contributions to health are presented. Phenolic compounds in rye, such as phenolic acids, alkylresorcinols and lignans, are concentrated in the outer layers of the grain. Phenolic acids are the major phenolic compounds in whole grain rye (103–300 mg/100 g grain), ferulic acid being the most abundant. Rye lignans are present at concentrations of 2 mg/100 g grain and had been shown to be converted by the intestinal microflora to the mammalian lignans enterodiol and enterolactone in human intervention studies. Alkylresorcinols (36–320 mg/100 g grain), which have been found to be incorporated into human erythrocyte membranes, are of particular interest due to their potential use as biomarkers of the intake of rye and wheat.
Flaxseed, the richest source of mammalian lignan precursors, such as secoisolariciresinol diglycoside (SD), has been shown over the short term to decrease some early markers of colon cancer risk. This study determined whether over the long term flaxseed still exerts a colon cancer protective effect, whether its effect may, in part, be due to its high content of SD and whether any change in beta-glucuronidase activity plays a role in the protective effect. Six groups of male Sprague-Dawley rats were fed for 100 days either a basal high fat (20%) diet (BD), BD supplemented with 2.5 or 5% flaxseed or 2.5 or 5% defatted flaxseed (equivalent to the respective flaxseed diets) or bD with a daily gavage of 1.5 mg SD. All rats were injected with a single dose of azoxymethane (15 mg/kg body wt) 1 week prior to commencing the dietary treatments. Urinary lignan excretion, which is an indicator of mammalian lignan production, was significantly increased in the flaxseed and defatted flaxseed groups. The total activity of cecal beta-glucuronidase was significantly increased in a dose-dependent manner by the flaxseed and defatted flaxseed diet groups. Compared with the control the number of aberrant crypts per focus was significantly reduced in the distal colon of the treated rats. Four microadenomas and two polyps were observed in the control group, but not in the treated groups. The total activity of beta-glucuronidase was positively correlated with total urinary lignan excretion and negatively with the total number of aberrant crypts and the total number of aberrant crypt foci in the distal colon. There were no significant differences between the flaxseed and the corresponding defatted flaxseed groups, It is concluded that flaxseed has a colon cancer protective effect, that it is due, in part, to SD and that the protective effect of flaxseed is associated with increased beta-glucuronidase activity.
The present study describes new methods for the measurement of oxidation products and antioxidant potential of low density lipoproteins (LDL).
LDL is isolated by precipitation with buffered heparin. The assay for LDL oxidation products (LDL-BDC) is based on determination of baseline levels of conjugated dienes (BDC) in lipids extracted from LDL. The assay for antioxidant potential of LDL (LDL-TRAP) is based on the ability of LDL to trap peroxyl radicals.
LDL-BDC was found to increase linearly over a range from 100 to 1750 microL, LDL-TRAP from 250 to 1750 microL of serum taken for precipitation. For LDL-BDC, the CV was 4.4% and 4.5% for within- and between-assay precision, respectively. For the LDL-TRAP, the CV was 8.1% and 8.7% for within- and between-assay precisions, respectively. Freezing of the serum (2 weeks at -70 degrees C) did not affect LDL-BDC or LDL-TRAP levels. A negative correlation was found to exist between the LDL-BDC and LDL-TRAP values. LDL-BDC and LDL-TRAP values were at the same level in both sexes. The LDL-BDC was found to increase with age. Short-term intervention with antioxidants increased LDL-TRAP substantially, but did not affect the LDL-BDC level.
These methods are fast and simple to perform, and can, therefore, be applied to clinical purposes.
Inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene initiates colorectal neoplasia. One of the biochemical activities associated with the APC protein
is down-regulation of transcriptional activation mediated by β-catenin and T cell transcription factor 4 (Tcf-4). The protein
products of mutant APC genes present in colorectal tumors were found to be defective in this activity. Furthermore, colorectal tumors with intact
APC genes were found to contain activating mutations of β-catenin that altered functionally significant phosphorylation sites.
These results indicate that regulation of β-catenin is critical to APC's tumor suppressive effect and that this regulation
can be circumvented by mutations in either APC or β-catenin.
The adenomatous polyposis coli (APC) tumor suppressor protein binds to β-catenin, a protein recently shown to interact with
Tcf and Lef transcription factors. The gene encoding hTcf-4, a Tcf family member that is expressed in colonic epithelium,
was cloned and characterized. hTcf-4 transactivates transcription only when associated with β-catenin. Nuclei of APC−/− colon carcinoma cells were found to contain a stable β-catenin-hTcf-4 complex that was constitutively active, as measured
by transcription of a Tcf reporter gene. Reintroduction of APC removed β-catenin from hTcf-4 and abrogated the transcriptional transactivation. Constitutive
transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.
Epidemiological studies suggest that high consumption of red meat and saturated fat and low consumption of fiber are associated with an increased risk of colon cancer. Therefore, we studied whether diets high in red meat or high in different grain fibers as well as inulin, polydisperse beta(2-->1) fructan, could affect the formation of intestinal polyps in Apc(Min) mice. Min mice were fed the following high-fat (40% of energy) diets for 5-6 weeks; a high-beef diet and a casein-based diet without added fiber or casein-based diet with 10% (w/w) oat, rye or wheat bran, or 2.5% (w/w) inulin. One group had a normal low-fat AIN93-G diet. The mice fed the rye-bran diet had the lowest number of polyps in the distal small intestine [15.4 +/- 8.7 (mean +/- SD)], and in the entire intestine (26.4 +/- 12.1). The rye-bran group differed significantly (P = 0. 001-0.004) from the beef group (36.6 +/- 9.4 and 52.8 +/- 13.2). In addition, the beef group differed significantly from the AIN93-G group (P = 0.009) and also from the wheat-bran group (21.0 +/- 6.1 and 35.0 +/- 8.2; P = 0.02) in the distal small intestine. The inulin group (32.9 +/- 14.3 and 49.3 +/- 16.3), on the other hand, was close to the beef group and it differed significantly from the rye-bran group in the distal small intestine. The number of animals bearing tumors in the colon + caecum was only 33% in the rye-bran group when compared with 89% in the beef and 100% in the inulin groups. The mice fed the rye-bran and beef diets had the lowest levels of cytosolic beta-catenin (0.60 +/- 0.42 and 0.67 +/- 0.26) and they differed significantly (P = 0.040 and 0.062) from the mice fed the oat-bran diet (1.46 +/- 0.43). No differences between groups in expression of protein kinase C (PKC) alpha, betaII, delta and zeta were found. The four PKC isozymes were positively correlated with cytosolic beta-catenin levels (r = 0.62-0.68; P < 0.0001).
The potential for the extraction of the plant lignan hydroxymatairesinol (HMR) in large scale from Norway spruce (Picea abies) has given us the opportunity to study the metabolism and biological actions of HMR in animals. HMR, the most abundant single component of spruce lignans, was metabolized to enterolactone (ENL) as the major metabolite in rats after oral administration. The amounts of urinary ENL increased with the dose of HMR (from 3 to 50 mg/kg), and only minor amounts of unmetabolized HMR isomers and other lignans were found in urine. HMR (15 mg/kg body wt po) given for 51 days decreased the number of growing tumors and increased the proportion of regressing and stabilized tumors in the rat dimethylbenz[a]anthracene-induced mammary tumor model. HMR (50 mg/kg body wt) did not exert estrogenic or antiestrogenic activity in the uterine growth test in immature rats. HMR also showed no antiandrogenic responses in the growth of accessory sex glands in adult male rats. Neither ENL nor enterodiol showed estrogenic or antiestrogenic activity via a classical alpha- or beta-type estrogen receptor-mediated pathway in vitro at < 1.0 microM. HMR was an effective antioxidant in vitro.
Edible plants contain a number of natural compounds which mimic the biological effects of oestrogens by virtue of their ability to bind to and activate the nuclear oestrogen receptors. These hormone-like diphenolic phyto-oestrogens of dietary origin include isoflavonoids, coumestans and lignans. Our interest in these phyto-oestrogens derives from the results of epidemiological studies on diet and Western diseases including hormone-dependent cancers as well as coronary heart disease. Incidences of the diseases in question are lower in peoples of Asia compared to inhabitants of industrialized American and European countries. Using isotope dilution gas chromatography-mass spectrometry method we have identified and measured in foods the precursors of the biologically active compounds detected in plasma of subjects living in areas with low cancer incidence. Biochanin A, formononetin, daidzein, genistein, and coumestrol, and the lignans matairesinol and secoisolariciresinol have been found to possess oestrogenic, anti-oestrogenic, antioxidative, antiviral, antibacterial, insecticidal or fungistatic properties and they have been shown to be antiproliferative in relation to many types of tumours in cell culture. We report quantitative results for these plant oestrogens measured in soybeans and other legumes, oilseeds and nuts, grain and cereals, berries and fruits, cruciferous, allium and other vegetables, and beverages such as tea and coffee.
A computational strategy for the deconvolution of complex spectra involving scalar multiplet patterns is presented. This approach fits spectra that can be composed of single resonances as well as scalar coupling multiplets for which resonance frequencies, intensities, and lineshape parameters can be optimized. For multiplets, the coupling constant also is optimized. Any external information about the optimizable parameters can be taken into account as external constraints. A lineshape described by absorptive and dispersive Lorentzian and Gaussian contributions and the baseline with up to 40 Fourier and polynomial terms can likewise be optimized. The effectiveness of the procedure is assessed on the basis of computer simulated deconvolutions of a composite of 1J(13C−2H) multiplets arising from a mixture of all possible 13C−2H isotopomers of deuterated L-[3-13C]lactate generated from cell preparations incubated with D-[1-13C]glucose in D2O, which was analyzed previously with a manual deconvolution procedure (R. Willem, M. Biesemans, F. Kayser, W. J. Malaisse, Magn. Reson. Med. 31, 259–267 (1994)). The use of constraints is shown to lead to an improvement in the results. The fitting strategies and the importance of the baseline as an origin of bias are discussed.
To investigate the effects of flaxseed supplementation (13.5 g/d) on lignan and sex hormone metabolism, six healthy young men were studied. The subjects consumed whole wheat/flaxseed (WWF) bread for six weeks. Three-day dietary records, fasting blood samples and 24-h urine collections were obtained. Energy intake remained constant. Urinary levels of enterodiol and enterolactone were significantly higher following 1, 2, 4 and 6 weeks of WWF feeding, exceeding by 7–28 fold the amounts found at baseline. Urinary enterolactone excretion was 5–10 fold greater than enterodiol excretion. Flaxseed supplementation yielded, on average, 4.2 μmol urinary lignans/g flaxseed flour/d. No significant change in plasma total testosterone, free testosterone or sex-hormone-binding globulin was observed. Although dietary lignans may influence hormone-dependent cancer incidence by modulating the hormonal environment, an increase in short-term flaxseed consumption did not lead to significant differences in the hormonal milieu. Further study delineating the effect of lignans on steroid hormone metabolism and risk of hormone-dependent cancer is Warranted.
We studied the effects of different variables on luminol-enhanced chemiluminescence (CL) of whole blood, induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP), opsonized zymosan particles (OZP), or phosphate buffered saline (PBS). Use of correction factor based on blood neutrophil count and hemoglobin concentration decreased interindividual variation and improved normality of the frequency distributions of CL responses. In FMLP- and PBS-induced CL, day-to-day variation was not significant, but it was significant in OZP-induced CL. Although storage of blood samples for 8 hours decreased CL, the decrease was not evident in a study of initial activation, i.e. CL measured at one minute after application of FMLP. Our results suggest that FMLP-induced initial activation is well suited for epidemiological studies because it is easy to determine and is affected neither by day-to-day variation nor by storage of the blood samples for a few hours.
Lignans are a class of compounds with a dibenzylbutane skeleton which until recently had only been found in higher plants. The first lignans to be identified in humans and animals were trans 2,3-bis(3-hydroxybenzyl)-γ-butyrolactone (enterolactone and 2,3-bis(3-hydroxybenzyl) butane-1,4-diol (enterodiol). These structures differ from those of plant lignans by having aromatic rings substituted only in the meta position. Enterolactone and enterodiol are excreted in the urine and bile, predominantly as glucuronide conjugates, and intestinal microflora is required for their formation. It is not known, however, whether they are synthesized de novo by microrganisms or are formed from dietary precursors. We report here evidence that these mammalian lignans are formed by microbial action on precursor lignans which are present as dietary constituents of plant origin. Precursors are found in seeds of different species, being particularly abundant in linseed. From this source, 2,3-bis(3-methoxy-4-hydroxybenzyl) butane-1,4-diol (secoisolariciresinol) has been identified as a glycoside.
Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.
The aim of the present study was to investigate antioxidativity of the triphenylethylene antiestrogen toremifene. Toremifene and its structural analogues were studied for their ability to inhibit chain reactions of lipid peroxidation and to act as scavengers of free radicals in vitro, and the effects of toremifene were compared to those of the estrogens, tamoxifen and known antioxidants. Moreover, the in vivo antioxidativity of toremifene was tested in a long-term experiment with rats. The ability of toremifene to prevent lipid peroxidation was assayed in two different test systems. In the first assay (initiated with ascorbate/ADP-FeCl3, detection by the formation of TBA-reactive material) toremifene was found to act as an efficient membrane antioxidant with an IC50-value (18 microM) comparable to that of tamoxifen (26 microM) and alpha-tocopherol (43 microM). Toremifene derivatives 4-hydroxytoremifene (IC50 = 8 microM) and Fc 1159 (IC50 = 31 microM), as well as diethylstilbestrol (IC50 = 17 microM) were also active while estradiol showed only weak antioxidativity (IC50 = 300 microM) in this test system. In the other assay (peroxidation initiated with t-butylhydroperoxide, detection by luminol-enhanced chemiluminescence) toremifene prevented lipid peroxidation only at high concentrations (IC50 = 450 microM) but the metabolite 4-hydroxytoremifene (IC50 = 0.18 microM), estradiol (IC50 = 4.6 microM) and diethylstilbestrol (IC50 = 1.7 microM) showed potent antioxidant activity. The potency of 4-hydroxytoremifene even exceded that of alpha-tocopherol (IC50 = 2.0 microM) and butylated hydroxyanisole (IC50 = 1.1 microM). Toremifene was found to have some superoxide anion but no peroxyl radical scavenging activity. Interestingly, diethylstilbestrol turned out to be a potent scavenger of peroxyl radicals. Treatment of female Sprague-Dawley rats with toremifene (12 or 48 mg/kg) was found to decrease serum levels of lipid peroxides. This was seen at various time points (2 days, 5 weeks, 6 and 12 months) during long-term administration of toremifene to rats, and results obtained with two different methods (diene conjugation, TBA-reactive material) gave similar results. The present study thus showed that (i) like steroidal estrogens and tamoxifen toremifene is a potent membrane antioxidant in vitro, (ii) the antioxidant action of toremifene is not due to scavenging of free radicals and, importantly, (iii) toremifene acts antioxidatively also in living organisms in vivo.
Phyto-oestrogens are a group of naturally occurring chemicals derived from plants; they have a structure similar to oestrogen, and form part of our diet. They also have potentially anticarcinogenic biological activity. We did a case-control study to assess the association between phyto-oestrogen intake (as measured by urinary excretion) and the risk of breast cancer.
Women with newly diagnosed early breast cancer were interviewed by means of questionnaires, and a 72 h urine collection and blood sample were taken before any treatment started. Controls were randomly selected from the electoral roll after matching for age and area of residence. 144 pairs were included for analysis. The urine samples were assayed for the isoflavonic phyto-oestrogens daidzein, genistein, and equol, and the lignans enterodiol, enterolactone, and matairesinol.
After adjustment for age at menarche, parity, alcohol intake, and total fat intake, high excretion of both equol and enterolactone was associated with a substantial reduction in breast-cancer risk, with significant trends through the quartiles: equol odds ratios were 1.00, 0.45 (95% CI 0.20, 1.02), 0.52 (0.23, 1.17), and 0.27 (0.10, 0.69)--trend p = 0.009--and enterolactone odds ratios were 1.00, 0.91 (0.41, 1.98), 0.65 (0.29, 1.44), 0.36 (0.15, 0.86)--trend p = 0.013. For most other phytoestrogens there was a reduction in risk, but it did not reach significance. Difficulties with the genistein assay precluded analysis of that substance.
There is a substantial reduction in breast-cancer risk among women with a high intake (as measured by excretion) of phyto-oestrogens-particularly the isoflavonic phyto-oestrogen equol and the lignan enterolactone. These findings could be important in the prevention of breast cancer.
We investigated the effect of dietary supplementation with secoisolariciresinol diglycoside (SDG), a lignan precursor isolated from flaxseed, on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Four diets were compared: a basal diet (control group) and the basal diet supplemented with SDG at 73, 147 or 293 micromol/kg (equivalent to SDG provided in the 2.5, 5 or 10% flaxseed diet). Mice were fed the diet for 2 weeks before and after an intravenous injection of 0.6 x 10(5) tumor cells. At necropsy, the number and size of tumors that formed in the lungs were determined. The median number of tumors in the control group was 62, and those in the SDG-supplemented groups were 38, 36 and 29, respectively. The last was significantly different from the control (P < 0.01). Dietary supplementation with SDG at 73, 147 and 293 micromol/kg also decreased tumor size (tumor cross-sectional area and volume) in a dose-dependent manner compared with the control values. These results show that SDG reduced pulmonary metastasis of melanoma cells and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that dietary supplementation with SDG reduces experimental metastasis of melanoma cells in mice.
We studied the effects of a lignan, hydroxymatairesinol (HMR), and rye bran on intestinal tumor development in adenomatous polyposis colimultiple intestinal neoplasia (Apc)(Min) mice. HMR showed a strong chemopreventive effect in this animal model. The mean number of adenomas in the small intestine was significantly lower (26. 6+/-11.0, P<0.05) in mice fed the inulin and HMR when compared with the inulin and inulin/rye bran fed mice (39.6+/-8.9 and 36.0+/-7.4, respectively). HMR resulted in normalization of beta-catenin levels in adenoma tissue, indicating that HMR mediates its chemopreventive effect through the Apc-beta-catenin pathway. In the cytosolic fraction, beta-catenin level in adenoma tissue was significantly elevated (P=0.008-0.013) in all the diet groups as compared with that of the surrounding mucosa. In the nuclear fraction, beta-catenin in the inulin (3.15+/-2.9 relative units) and inulin/rye (5.17+/-6.94 relative units) groups was also significantly higher (P=0.003-0.009) in the adenoma tissue when compared with the surrounding mucosa (0.5+/-0.5 and 0.35+/-0.39 relative units). However, HMR was able to restore nuclear beta-catenin level of the adenoma tissue (0.41+/-0.25 relative units) to the level found in the surrounding mucosa (0.36+/-0.28 relative units).
Oxidative stress is implicated in neuronal loss associated with neurodegeneration such as in Parkinson's disease, Alzheimer's disease and age-related cognitive decline. Recent reports indicate that the consumption of flavonoid-rich fruits partly reverses the age-related neuronal and cognitive decline. In this study, cultured striatal neurons were exposed to oxidized lipids in the form of low-density lipoprotein (oxLDL) as a model for the induction of oxidative injury, and the abilities of phenolic antioxidants, flavonoids and hydroxycinnamic acid derivatives, to attenuate this neuronal damage were examined. OxLDL was demonstrated to enter neuronal cells and to be capable of eliciting neurotoxicity in a dose- and time-dependent manner, inducing DNA fragmentation and cell lysis. Flavonoids exert protective effects, which appear to be related to specific structural characteristics, particularly relevant being those defining their reduction potentials and partition coefficients. In summary, these data suggest a possible role for flavonoids in reducing neurodegeneration associated with chronic disorders in which oxidative stress is implicated.