Pinoresinol Research Articles

Abstract P143: Lignan Intake and Mortality Among Adults With Incident Type 2 Diabetes

Introduction: Lignans are polyphenolic compounds abundant in plant-based foods such as seeds, whole grains, and certain fruits and vegetables and may lead to better metabolic health. It remains elucidated regarding the role of lignan consumption in the etiology of premature deaths among diabetes patients. Hypothesis: We hypothesize that a higher intake of post-diagnosis lignans is associated with lower risk of mortality among individuals with incident type 2 diabetes (T2D). Design: Data from two prospective U.S. cohorts were analyzed, including the Nurses' Health Study (1984-2020) and Health Professionals Follow-up Study (1986-2022). Average daily consumption of total and individual lignans were calculated, and post-diagnosis lignan intakes were cumulatively averaged. Multivariable-adjusted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between post-diagnosis lignan intake and mortality. Results: Among 8,691 incident T2D cases contributing 119,065 person-years of follow-up, 4,502 deaths were documented, among which 1,379 cases were attributed to cardiovascular disease (CVD) and 777 to cancer. The pooled multivariable-adjusted HRs (95% CIs) of all-cause mortality comparing extreme quintiles of post-diagnosis lignan intake were 0.83 (0.74, 0.94) for total lignans, 0.87 (0.78, 0.96) for matairesinol (MAT), 0.77 (0.69, 0.86) for secoisolariciresinol (SECO), 0.92 (0.82, 1.03) for pinoresinol (PINO), and 0.92 (0.82, 1.03) for lariciresinol (LARIC). Higher post-diagnosis intakes of SECO were also significantly associated with lower CVD and cancer mortality. The HRs (95% CIs) of total mortality comparing extreme quintiles of changes in lignan intake from pre- to post-diagnosis were 0.84 (0.75, 0.93) for total lignans, 0.85 (0.76, 0.94) for MAT, and 0.79 (0.71, 0.89) for SECO. No significant associations were observed for PINO and LARIC. Stratified analyses showed that the associations of lignans were significantly stronger among non-white individuals. Conclusions: In conclusion, among individuals diagnosed with T2D, a higher intake of lignans, particularly SECO, was significantly associated with reduced overall, cardiovascular, and cancer mortality. Minority groups may particularly benefit from lignan intake, although further studies are warranted to substantiate this observation.

Comparative Study on the Absorption and Metabolism of Pinoresinol and Pinoresinol-4-O-β-D-Glucopyranoside in Mice.

Lignans are a group of phenolic compounds commonly found in plants, often in the form of glycosides. This study investigates the differences in the digestion, absorption, and metabolism of lignans and their glucosides using pinoresinol (PIN) and pinoresinol-4-O-β-D-glucopyranoside (PMG). After oral administration mice PIN and PMG with a dose of 0.1 µmolkg-1 . The results showed that the stomach and small intestine rapidly absorbe PIN and PMG in their prototype form. After oral administration of 0.25 h, serum levels of PIN and PMG reach peak values of 61.14 and 52.97 ngmL-1 , respectively. This indicates a faster PIN absorption rate than PMG, likely due to the glycosides attach to the parent compound, with concentrations of 1574.14 and 876.75 ngg-1 , respectively. Pharmacokinetic analysis reveals that PIN has a greater area under the curve and a longer half-life than PMG in serum and liver. Moreover, mice in the PIN group exhibit higher metabolite levels in the serum and liver compared to those in the PMG group. The deglycosylation process that occurs during the pickling of white radish facilitates the absorption and metabolism of the lignans fraction in the body.

Comparison of Pinoresinol and its Diglucoside on their ADME Properties and Vasorelaxant Effects on Phenylephrine-Induced Model.

Pinoresinol (PINL) and pinoresinol diglucoside (PDG), two natural lignans found in Eucommia ulmoides Oliv. (Duzhong), have several pharmacological activities. However, there is no report available on their absorption, distribution, metabolism, and elimination (ADME) properties. Given the possible wide spectrum of their application in therapeutic areas, this area should be investigated. This work studied the in vitro ADME properties of PDG and PINL, including their kinetic solubility, permeability across monolayer cells (PAMPA), protein binding, and metabolic stabilities in liver microsomes. The in vivo pharmacokinetic study and in vitro vasorelaxant effects on isolated phenylephrine-induced aortic rings of PINL and PDG were also investigated. It was found that both of their kinetic solubility in PBS (pH 7.4) was greater than 100 μM, indicating that they are both soluble compounds. The permeability investigations (P eff) by PAMPA indicated that PINL had higher permeability than PDG (p < 0.05). Both components represented moderate plasma protein binding activities (average binding rate in human plasma: PINL 89.03%, PDG 45.21%) and low metabolic rate (t 1/2 in human liver microsome: PINL 1509.5 min, PDG 1004.8 min). Furthermore, the results of pharmacokinetic studies indicated that PINL might be eliminated less quickly than PDG from the rat plasma, and its cumulative urinary excretion was much lower than that of PDG. The phenylephrine-induced aortic rings demonstrated concentration-dependent vasorelaxation in PDG, PINL, or their combination group. The vasorelaxant effects of PINL were more obvious than those of PDG, whereas the vasorelaxant effect of the combinations was significantly better than that of the single component (p < 0.05). The similarity or difference between PINL and its diglucoside in these pharmaceutical aspects may offer valuable insights into the further exploration of lignans and might contribute to relevant studies involving natural products with similar molecular structure and their glucosides.

Olive Oil Lignan (+)-Acetoxypinoresinol Peripheral Motor and Neuronal Protection against the Tremorgenic Mycotoxin Penitrem A Toxicity via STAT1 Pathway.

Penitrem A, PA, is an indole diterpene alkaloid produced by several fungal species. PA acts as a selective Ca2+-dependent K-channels (Maxi-K, BK) antagonist in brain, causing motor system dysfunctions including tremors and seizures. However, its molecular mechanism at the peripheral nervous system (PNS) is still ambiguous. The Mediterranean diet key ingredient extra-virgin olive oil (EVOO) provides a variety of minor bioactive phenolics. (+)-Pinoresinol (PN) and (+)-1-acetoxypinoresinol (AC) are naturally occurring lignans in EVOO with diverse biological activities. AC exclusively occurs in EVOO, unlike PN, which occurs in several plants. Results suggest that PA neurotoxicity molecular mechanism is mediated, in part, through distortion of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. PA selectively activated the STAT1 pathway, independently of the interferon-γ (IFN-γ) pathway, in vitro in Schwann cells and in vivo in Swiss albino mice sciatic nerves. Preliminary in vitro screening of an EVOO phenolic compounds library for the ability to reverse PA toxicity on Schwann cells revealed PN and AC as potential hits. In a Swiss albino mouse model, AC significantly minimized the fatality after intraperitoneal administration of PA fatal doses and normalized most biochemical factors by modulating the STAT1 expression. The olive lignan AC is a novel lead that can prevent the neurotoxicity of food-contaminating tremorgenic indole alkaloid mycotoxins.

Pinoresinol promotes MC3T3‑E1 cell proliferation and differentiation via the cyclic AMP/protein kinaseA signaling pathway.

Estradiol (E2) is a first-line drug for osteoporosis (OP) treatment via promotion of osteoblastic proliferation and differentiation. However, a long-term use of E2 would produce side effects thus, it is imperative to discover safer and more effective drugs. Pinoresinol (PINO) has a similar chemical structure to E2. The present study aimed to investigate whether PINO could promote osteoblastic proliferation and differentiation and the potential mechanisms. After treatment with 0.1 µg/l PINO for 2 days, MC3T3-E1 cell migration was assessed by wound healing assay. Estrogen (E2) treatment served as a positive control. RT-qPCR and western blotting were used for mRNA and protein expression analyses. Alkaline phosphatase (ALP) activity assay and Alizarin red staining were performed to investigate the calcification and mineralization, and the cyclic AMP (cAMP) level was detected by enzyme-linked immunosorbent assay (ELISA). H89, an inhibitor of protein kinase A (PKA), was introduced to verify the role of cAMP/PKA in the effect of PINO on MC3T3-E1 cells. Cell viability was the highest under 48 h of 0.1 µg/l PINO treatment. After treatment with PINO, a significant increase was observed in the migration rate and the expression of collagen type I (Col-I), ALP, osteopontin (OPN), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein-2 (BMP-2) (P<0.01). The ALP activity and Alizarin red size in PINO and E2 groups were notably increased. The increased cAMP, PKA and phosphorylated cAMP response element-binding protein (CREB) levels were also observed in the PINO group. Furthermore, H89 co-treatment abolished the positive effects of PINO on cell viability and migration. PINO had similar effects to E2 on the osteoblastic proliferation and differentiation, and these positive effects may be attributed to the regulation of the cAMP/PKA signaling pathway.

RNAi-mediated silencing of pinoresinol lariciresinol reductase in Linum album hairy roots alters the phenolic accumulation in response to fungal elicitor

Lignans are diphenolic compounds produced in plants via coupling of two coniferyl alcohol molecules with the aid of a dirigent protein to form pinoresinol (PINO). The latter is reduced via lariciresinol (LARI) to secoisolariciresinol by the bifunctional pinoresinol–lariciresinol reductase (PLR). In this study, we clarified the consequences of altered lignan biosynthesis on amino acids, phenolics compounds and lignin in the hairy roots of Linum album with an ihpRNAi construct to silence PLR gene expression. Down-regulation of PLR-La1 resulted in up to an 8.3 and 3.3-time increased PINO and LARI content respectively, and reduced levels of podophyllotoxin (PTOX) and 6-methoxy podophyllotoxin (6-MPTOX). By Suppression of PLR expression, the metabolites belonging to shikimate and phenylpropanoid pathways are conducted to phenolic compounds and lignin accumulations. Although PINO and LARI were induced in response to fungal elicitor, the accumulation of PTOX and 6-MPTOX did not occur in PLR down-regulated roots. Our result also demonstrated variation in amino acids, phenolic compounds and lignin levels in presence of the fungal elicitation in PLR down regulated-roots. This data assert the accumulation of aryltetralin lignans in interactions with plant pathogens by PLR activity and the importance this enzyme for defense against pathogens in L. album.

Lignan and flavonoid support the prevention of cinnamon against oxidative stress related diseases

BackgroundOxidative stress contributes to the pathogenesis of many human diseases. Cinnamon is a worldwide used spice, dietary supplement and traditional medicine, and is used for the therapy of oxidative stress related diseases. A well-established concept is that the functions of cinnamon preventing oxidative stress-induced diseases are attributed to the occurrence of cinnamaldehyde and its analogues. HypothesisIn our continuous searching of natural molecules with antioxidant capacity, we have found that cinnamaldehyde and its analogues in cinnamon are weak inhibitors of oxidative stress, and thus we speculate that there are novel and/or potent molecules inhibiting oxidative stress in cinnamon. Study design and methodsA systemic phytochemical investigation of cinnamon using column chromatography was performed to identify the chemical constituents of cinnamon, and then their capacity of inhibiting oxidative stress and action of mechanism targeting Nrf2 pathway were investigated using diverse bioassay, including NAD(P)H: quinone reductase (QR) assay, immunoblot analysis, luciferase reporter gene assay, immunofluorescence and flow cytometry. ResultsCinnamon improved the intracellular antioxidant capacity. A systemic phytochemical investigation of cinnamon gave the isolation of twenty-two chemical ingredients. The purified constituents were tested for their potential inhibitory effects against oxidative stress. Besides cinnamaldehyde analogues, a lignan pinoresinol (PRO) and a flavonol (-)-(2R,3R)-5,7-dimethoxy-3′, 4′-methylenedioxy-flavan-3-ol (MFO) were firstly identified to be inhibitors of oxidative stress. Further study indicated that PRO and MFO activated Nrf2-mediated antioxidant response, and protected human lung epithelial cells against sodium arsenite [As(III)]-induced oxidative insults. ConclusionThe lignan PRO and the flavonoid MFO are two novel Nrf2 activators protecting tissues against oxidative insults, and these two constituents support the application of cinnamon as an agent against oxidative stress related diseases.

Are Total and Individual Dietary Lignans Related to Cardiovascular Disease and Its Risk Factors in Postmenopausal Women? A Nationwide Study.

The study objectives were to examine total and individual lignan intakes and their dietary sources in postmenopausal Polish women and to investigate the relationship between lignan intake and the prevalence of cardiovascular disease (CVD), hypertension, hypercholesterolemia and central obesity. A total of 2599 postmenopausal women, participants of the Multi-centre National Population Health Examination Surveys (WOBASZ and WOBASZ II) were selected. Of them, 916 had a history of CVD. Nutritional data were collected using a single 24-h dietary recall. Data on lignan content in food, i.e., lariciresinol (LARI), matairesinol (MAT), pinoresinol (PINO) and secoisolariciresinol (SECO), were collected from the available lignan databases. In postmenopausal women, total and individual lignan intakes (SECO, PINO, MAT) were not associated with the prevalence of CVD and its risk factors. The intake of LARI was linked by 30% to the reduced odds for hypercholestrolemia. This study reinforces the existing concept that dietary total lignans are not associated with the prevalence of CVD, and provides further evidence that they are not linked to CVD risk factors such as hypertension, hypercholesterolemia and central obesity. However, the intake of LARI should be taken into consideration in further studies with regard to its potentially beneficial effect in hypercholesterolemia.

Study on anti-inflammatory activity of the main component of Girald Daphne Bark in vitro

Objective To investigate the anti-inflammatory activity of the main active ingredients in thedried stem bark of Daphne giraldii Nitsche. Methods Severialchemical compounds like vladinol D, pinoresinol, daphneticin, daphnoretin, daphnetin, giraloid A and giraldoid B were isolated from the stem barks. The CCK-8 experiemnts were analyzed for the cytotoxicity study. The cells were divided into the control group, the model group and the treatment group according to random number table method. The control group and the model group were added with 50 μl culture medium. Moreover, treatment group was added with different concentrations (50.00, 25.00, 12.50, 6.25, 3.12 μg/ml) of the solutions of giraloid A, giraldoid B and daphneticin. Then, RAW264.7 cells were treated with 50 μl LPS (4 μg/ml) for 24 h in the model group and treatment group. Griess reagent was used to determine the amount of NO release, and the secretion of TNF-α was detected by ELISA kit. Results Cytotoxicity test indicated that giraldoid A (50.00 μg/ml), giraldoid B (50.00 μg/ml) and daphneticin (50.00 μg/ml) showed noobvious cytotoxicity. Giraldoid B (12.50, 25.00, 50.00 μg/ml) could inhibit the production of NO (271.86% ± 20.92%, 256.48% ± 20.92%, 199.31% ± 15.16% vs. 358.62% ± 28.64%) and TNF-α (647.87% ±115.79%, 618.42% ± 87.52%, 588.33% ± 87.94% vs. 1 035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Giraldoid A (25, 50 μg/ml) could inhibit the production of NO (234.99% ± 34.28%, 167.36% ± 25.76% vs. 358.62%±28.64%) and TNF-α (691.76% ± 60.37%, 534.01% ± 41.60% vs. 1 035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Daphneticin (12.5, 25, 50 μg/ml) could inhibit the production of NO (283.89% ± 36.69%, 243.08% ± 48.19%, 225.92% ± 33.67% vs. 358.62% ± 28.64%) and TNF-α (713.77% ± 121.96%, 670.62% ± 18.70% vs. 1 035.06% ± 58.29%) in RAW264.7 induced by LPS compared with the model group. Conclusions Giraldoid A, giraldoid B and daphneticin exhi bited anti-inflammatory effect through inhibiting the release of NO and the production of TNF-α in RAW264.7 induced by LPS. Key words: Daphne giraldiiNitsche; Inflammation; Lipopolysaccharides; Nitric oxide; Tumor necrosis factor-alpha

Optimized conversion of antiproliferative lignans pinoresinol and epipinoresinol: Their simultaneous isolation and identification by centrifugal partition chromatography and high performance liquid chromatography.

High amount of the valuable lignan pinoresinol (PR) was determined in Carduus nutans fruit (7.8mg/g) for the first time. A preparative separation method using two consecutive, identical steps of centrifugal partition chromatography (CPC) was developed in order (i) to isolate PR and (ii) to subsequently isolate PR and its 7' epimer epipinoresinol (EPR) simultaneously after an optimized acid treatment which resulted in PR epimerization forming equal amounts of PR and EPR, from C. nutans fruit. As optimal conditions, a two-phase solvent system consisting of methyl tert-butyl ether:acetone:water (4:3:3, v/v/v) for CPC separation, and an acid treatment performed at 50°C for 30min for the epimerization were applied. Thus, 33.7mg and 32.8mg PR and EPR, in as high as 93.7% and 92.3% purity, were isolated from 10.0gC. nutans fruit, representing 86.4% and 84.1% efficiency, respectively. Conversion characteristic of PR and EPR in acidic medium, determined as a function of time and temperature of acid treatment provides their unambiguous identification by on-line high performance liquid chromatography (HPLC). Antiproliferative assay of isolated PR and EPR in two different types of colon cancer cell lines (HCT116 and SW480) confirmed that both epimers caused a more significant decrease of viability in HCT116 cells than in SW480 cells, suggesting their similar mechanism of antiproliferative action.

Regulative effect of pinoresinol diglucoside on gene of ESF-1 cells collagen secretion

Objective To study the pinoresinol diglucoside (PDG) on gene regulation role of ESF-1 cells in collagen secretion, to reveal PDG repair mechanisms on scalded skin. Methods The cells cultured in vitro were divided into the control group, the estradiol group and the three different PDG doses groups. The concentration of the high, medium and low dose groups were 100, 10, 1 μmol/L, and that of estradiol group were 10-3 μmol/L. The activity of proliferation was detected by MTT. Then collagen type I (Col I), collagen type Ⅲ (Col Ⅲ), tissue inhibitors of metalloproteinase 1 (TIMP-1), tissue inhibitors of metalloproteinase 2 (TIMP-2) and matrix metalloproteinase 1 (MMP-1) expression levels of mRNA after administration of cells were detected by RT-PCR. Results Compared with the control group, the proliferation of ESF-1 cells (0.559 ± 0.027, 0.552 ± 0.034 vs. 0.489 ± 0.027, P<0.05) in the estradiol and medium-dose PDG was significantly higher. The expression level of mRNA of ColⅠ(0.958 ± 0.021, 0.929 ± 0.031, 0.916 ± 0.015 vs. 0.844 ± 0.022), Col Ⅲ (0.783 ± 0.038, 0.918 ± 0.021, 0.855 ± 0.017 vs. 0.678 ± 0.024), TIMP-1 (0.939 ± 0.025, 0.889 ± 0.036, 0.853 ± 0.015 vs. 0.780 ± 0.023), TIMP-2 (0.507 ± 0.024, 0.655 ± 0.037, 0.572 ± 0.025 vs. 0.405 ± 0.062) in the estradiol, low-, medium-dose PDG groups were significantly higher than those in the control group (P<0.05 or P<0.01). Besides, the MMP-1 (0.343 ± 0.038, 0.407 ± 0.046, 0.435 ± 0.037 vs. 0.519 ± 0.041) mRNA expression level in the middle and low dose PDG groups significantly decrease (P<0.05 or P<0.01). Conclusions The PDG could enhance the activity of ESF-1 cell proliferation, increase the expression of related collagen and tissue inhibitor of metalloproteinases and inhibit that of matrix metalloproteinases to repair scalded skin. Key words: Burns; Pinoresinol diglucoside; Collagen; Matrix metalloproteinases

Rapid Determination of Pinoresinol Diglucoside and Geniposidic Acid in Eucommia ulmoides with Near Infrared Spectroscopy Combined with

Rapid Determination of Pinoresinol Diglucoside and Geniposidic Acid in Eucommia ulmoides with Near Infrared Spectroscopy Combined with

Lignan enhancement in hairy root cultures of Linum album using coniferaldehyde and methylenedioxycinnamic acid

ABSTRACTFeeding experiments with hairy root cultures of Linum album have established that the extracellular coniferaldehyde is a good precursor for production of two lignans: lariciresinol (LARI) and pinoresinol (PINO). The accumulation of the LARI, PINO, and podophyllotoxin (PTOX) in hairy roots were enhanced about 14.8-, 8.7-, and 1.5-fold (107.61, 8.7 and 6.42 µg g−1 Fresh Wight), respectively, by the addition of coniferaldehyde (2 mM) to the culture media (after 24 hr). This result was correlated with an increase pinoresinol/lariciresinol reductase (PLR) expression gene and cinnamyl alcohol dehydrogenase (CAD) activity in the fed hairy roots. Adding 3,4-(methylendioxy)cinnamic acid (MDCA) precursor did not influence on the lignans accumulation, but the lignin content of the hairy roots was increased. Moreover, the expression genes of phenylalanine ammonialyase (PAL), CAD, and cinnamoyl-CoA reductase (CCR) were influenced after feeding hairy roots with MDCA.

Gold nanoparticle-lignan complexes inhibited MCF-7 cell proliferation in vitro: a novel conjugation for cancer therapy.

Nanoparticles, including gold nanoparticles (AuNP), have been used in imaging in cancer treatment and as therapeutic agents and drug delivery vehicles. Particularly lignans, also called phytoestrogens, have strong effects on the treatment of carcinomas due to their antiestrogenic, antiangiogenic and proapoptotic mechanism. The aim of this study is to investigate the antiproliferative effects of three lignans-AuNP conjugates, pinoresinol (PINO), lariciresinol (LARI) and secoisolariciresinol (SECO), on the MCF-7 cell lines. For this purpose, first, thiolated β-cyclodextrin (β-CD) was synthesized to achieve a surface modification of AuNP, and then the β-CD modified AuNP was characterized using the transmission electron microscopy (TEM), UV-Visible and Nuclear Magnetic Resonance (NMR) spectroscopy. Then, the selected lignans were conjugated to the β-CD-modified AuNP, and the antiproliferative effect of these conjugates was monitored. The results suggest that when compared to their non-conjugated forms, the AuNP-bound lignan conjugates prevented the proliferation of the MCF-7 cells significantly. Therefore, these AuNP-conjugated derivatives can be new candidate agents for breast cancer therapy.

Pinoresinol Inhibits Proliferation and Induces Differentiation on Human HL60 Leukemia Cells

Pinoresinol (PIN), one of the simplest lignans, is the precursor of other dietary lignans that are present in whole-grain cereals, legumes, fruits, and other vegetables. Several experimental and epidemiological evidences suggest that lignans may prevent human cancer in different organs. In this study we investigated the chemopreventive properties of PIN on cell lines derived from different sites either expressing or not the functional tumor suppressor protein p53. It was found that PIN inhibited the proliferation of p53 wild type colon and prostate tumor cells (HCT116 and LNCaP) while in breast cells the inhibition of growth was observed only in p53 mutant cells (MDA-MB-231). A potent antiproliferative activity of PIN was also observed on p53 null cells HL60 (IC50% 8 μM), their multidrug resistant variant HL60R (IC50% 32 μM) and K562. On HL60 cells, PIN caused a block of cell cycle in the G0/G1 phase, induced a weak proapoptotic effect but it was a good trigger of differentiation (NBT reduction and CD11b expression). PIN caused an upregulation of the CDK inhibitor p21WAF1/Cip1 both at mRNA and protein levels so suggesting that this could be a mechanism by which PIN reduced proliferation and induced differentiation on HL60 cells.

Validation of an Electrochemical Detection–High-Performance Liquid Chromatography Method for Simultaneous Determination of Lignans in Flaxseed (Linum usitatissimum L.)

Flaxseed is a major source of lignans, which are important bioactive compounds. The aims of this work were to validate a liquid chromatographic method for the rapid and simultaneous determination of the main lignans in flaxseed using high-performance liquid chromatography coupled with electrochemical detection and to analyze the composition of commercial samples of flaxseed. The performance criteria of the proposed method demonstrate that the method can be used for the analysis of secoisolariciresinol diglucoside (SDG), secoisolariciresinol (SECO), matairesinol (MATA), pinoresinol (PINO), lariciresinol (LARI), hydroxymatairesinol (HYDROXY), and isolariciresinol (ISOLARI) in flaxseeds at suitable levels. Calibration curves were determined for six different concentrations of standard solutions injected in triplicate. The sensitivity of the calibration curve was evaluated considering the confidence intervals of the intercept and slope. The limit of detection and limit of quantification were 7.4 and 10.9 μg/l, respectively, for LARI and 17.7 and 37.5 μg/l, respectively, for MATA. The relative standard deviation of repeatability values were lower than 2.59 %, which are acceptable because the Horwitz ratio values were 0.1 for all of the lignans. The recoveries of lignans were in the range of 74–100 % of SECO, which are consistent with the literature. The precision of the proposed method was determined by analyzing four flaxseed samples of different years and varieties. SDG was the main lignan present in all the samples, followed by ISOLARI and HYDROXY.

Dietary intake and main sources of plant lignans in five European countries

BackgroundDietary intakes of plant lignans have been hypothesized to be inversely associated with the risk of developing cardiovascular disease and cancer. Earlier studies were based on a Finnish lignan database (Fineli®) with two lignan precursors, secoisolariciresinol (SECO) and matairesinol (MAT). More recently, a Dutch database, including SECO and MAT and the newly recognized lignan precursors lariciresinol (LARI) and pinoresinol (PINO), was compiled. The objective was to re-estimate and re-evaluate plant lignan intakes and to identify the main sources of plant lignans in five European countries using the Finnish and Dutch lignan databases, respectively.MethodsForty-two food groups known to contribute to the total lignan intake were selected and attributed a value for SECO and MAT from the Finnish lignan database (Fineli®) or for SECO, MAT, LARI, and PINO from the Dutch database. Total intake of lignans was estimated from food consumption data for adult men and women (19–79 years) from Denmark, Finland, Italy, Sweden, United Kingdom, and the contribution of aggregated food groups calculated using the Dutch lignin database.ResultsMean dietary lignan intakes estimated using the Dutch database ranged from 1 to 2 mg/day, which was approximately four-fold higher than the intakes estimated from the Fineli® database. When LARI and PINO were included in the estimation of the total lignan intakes, cereals, grain products, vegetables, fruit and berries were the most important dietary sources of lignans.ConclusionTotal lignin intake was approximately four-fold higher in the Dutch lignin database, which includes the lignin precursors LARI and PINO, compared to estimates based on the Finnish database based only on SECO and MAT. The main sources of lignans according to the Dutch database in the five countries studied were cereals and grain products, vegetables, fruit, berries, and beverages.

Among Plant Lignans, Pinoresinol Has the Strongest Antiinflammatory Properties in Human Intestinal Caco-2 Cells1–3

AbstractDietary lignans show some promising health benefits, but little is known about their fate and activities in the small intestine. The purpose of this study was thus to investigate whether plant lignans are taken up by intestinal cells and modulate the intestinal inflammatory response using the Caco-2 cell model. Six lignan standards [secoisolariciresinol diglucoside (SDG), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol, matairesinol (MAT), and hydroxymatairesinol] and their colonic metabolites [enterolactone (ENL) and enterodiol] were studied. First, differentiated cells were exposed to SDG, SECO, PINO, or ENL at increasing concentrations for 4 h, and their cellular contents (before and after deconjugation) were determined by HPLC. Second, in IL-1βstimulated confluent and/or differentiated cells, lignan effects were tested on different soluble proinflammatory mediators quantified by enzyme immunoassays and on the NF-κB activation pathway by using cells transiently transfected. SECO, PINO, and ENL, but not SDG, were taken up and partly conjugated by cells, which is a saturable conjugation process. PINO was the most efficiently conjugated (75% of total in cells). In inflamed cells, PINO significantly reduced IL-6 by 65% and 30% in confluent and differentiated cells, respectively, and cyclooxygenase (COX)-2derived prostaglandin E2by 62% in confluent cells. In contrast, MAT increased significantly COX-2derived prostaglandin E2in confluent cells. Moreover, PINO dose-dependently decreased IL-6 and macrophage chemoattractant protein-1 secretions and NF-κB activity. Our findings suggest that plant lignans can be absorbed and metabolized in the small intestine and, among the plant lignans tested, PINO exhibited the strongest antiinflammatory properties by acting on the NF-κB signaling pathway, possibly in relation to its furofuran structure and/or its intestinal metabolism.

Molecular cloning and characterization of the gene encoding pinoresinol synthase from Tibet Dysosma

Two molecules of coniferyl alcohols are dimerized to form a molecule of pinoresinol , a precursor of podophyllotoxin – antiviral and antitumor agent. The process is catalyzed by pinoresinol synthase (PS). In the present study, the full-length cDNA encoding PS (designated as DtPS) was isolated and characterized from Tibet Dysosma, Dysosma tsayuensis Ying. The full-length DtPS cDNA was 798 bps, and contains a 582-bp open reading frame encoding a 193-amino-acid polypeptide, with a calculated molecular mass of 21.5 kDa and an isoelectric point of 7.24. Comparative analysis indicated that DtPS was similar to other plant PSs in terms of base sequence. The gene tissue- expressing pattern analysis indicated that the expression of DtPS could be detected in all the detected organs including roots, rhizomes, leaves, petioles, flowers and fruits but at different levels. The highest expression level was found in petiole and in fruit, followed by the roots, and lastly by the rhizome, leaf and flower. Cloning and characterization of the PS gene from Tibet Dysosma will facilitate mapping biosynthesis of podophyllotoxin at the molecular level. Key words: Dysosma tsayuensis Ying, pinoresinol synthase, cloning, expression profile, podophyllotoxin.

Intake of the plant lignans matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol in relation to vascular inflammation and endothelial dysfunction in middle age-elderly men and post-menopausal women living in Northern Italy

Background and aimsIt has been suggested that lignan intake may decrease the risk for cardiovascular disease (CVD) by modifying traditional risk factors as well as aortic stiffness. However, the role of dietary lignans on the vascular system is largely unknown. The objective was to investigate whether dietary intake of plant lignans in a free-living population was associated with markers of vascular inflammation and function. Methods and ResultsWe performed a cross-sectional study in 242 (151 males) men and post-menopausal women. Anthropometric characteristics and lignan intake were evaluated. Soluble intercellular adhesion molecule-1 (sICAM-1), insulin, high-sensitive C-reactive protein, glucose, total cholesterol, HDL-cholesterol and triacylglycerols were measured in fasting blood samples. Brachial flow-mediated dilation (FMD) measurements were available for 101 subjects (56 males). Median (interquartile range) daily intake of matairesinol (MAT), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol (LARI), and total lignans was 20.9 μg (17.4), 335.3 μg (289.1), 96.7 μg (91.1), 175.7 μg (135.8), and 665.5 μg (413.7), respectively, as assessed by 3-day weighed food record. Plasma concentrations of sICAM-1 (whole sample) significantly decreased (mean (95%CI) = 358 μg/L (320–401), 276 μg/L (252–303), 298 μg/L (271–326), and 269 μg/L (239–303), P per trend 0.013) and FMD values (FMD sub-group) significantly increased (4.1% (2.2–6.0), 5.7% (4.3–7.2), 6.4% (4.9–7.8), and 8.1% (6.3–10.0), P per trend 0.016) across quartiles of energy-adjusted MAT intake, even after adjustment for relevant clinical and dietary variables. Intake of SECO was also inversely related to plasma sICAM-1 (P per trend 0.018), but not to FMD values. No relationship between intake of PINO, LARI or total lignans and either sICAM-1 or FMD values was observed. ConclusionsHigher MAT intakes in the context of a typical Northern Italian diet are associated to lower vascular inflammation and endothelial dysfunction, which could have some implications in CVD prevention.