lignans and Chronic-Disease

Dietary guidelines universally advise adherence to plant-based diets. Plant-based foods confer considerable health benefits, partly attributable to their abundant micronutrient (e.g., polyphenol) content. Interest in polyphenols is largely focused on the contribution of their antioxidant activity to the prevention of various disorders, including cardiovascular disease and cancer. Polyphenols are classified into groups, such as stilbenes, flavonoids, phenolic acids, lignans and others. Lignans, which possess a steroid-like chemical structure and are defined as phytoestrogens, are of particular interest to researchers. Traditionally, health benefits attributed to lignans have included a lowered risk of heart disease, menopausal symptoms, osteoporosis and breast cancer. However, the intake of naturally lignan-rich foods varies with the type of diet. Consequently, based on the latest humans' findings and gathered information on lignan-rich foods collected from Phenol Explorer database this review focuses on the potential health benefits attributable to the consumption of different diets containing naturally lignan-rich foods. Current evidence highlight the bioactive properties of lignans as human health-promoting molecules. Thus, dietary intake of lignan-rich foods could be a useful way to bolster the prevention of chronic illness, such as certain types of cancers and cardiovascular disease.

Topics: Antioxidants; Biological Products; Chronic Disease; Databases, Chemical; Diet; Food Analysis; Health Promotion; Humans; Lignans; Phenols; Phytoestrogens; Plants, Edible; Recommended Dietary Allowances

Functional foods describe the importance of foods in promoting health and preventing diseases aside their primary role of providing the body with the required amount of essential nutrients such as proteins, carbohydrates, vitamins, fats, and oils needed for its healthy survival. This review explains the interaction of functional food bioactive compounds including polyphenols (phenolic acids [hydroxybenzoic acids and hydroxycinnamic acids], flavonoids [flavonols, flavones, flavanols, flavanones, isoflavones, proanthocyanidins], stilbenes, and lignans), terpenoids, carotenoids, alkaloids, omega-3 and polyunsaturated fatty acids, among others with critical enzymes (α- amylase, α- glucosidase, angiotensin-I converting enzyme [ACE], acetylcholinesterase [AChE], and arginase) linked to some degenerative diseases (type-2 diabetes, cardiovascular diseases [hypertension], neurodegenerative diseases [Alzheimer's disease] and erectile dysfunction). Different functional food bioactive compounds may synergistically/additively confer an overwhelming protection against these degenerative diseases by modulating/altering the activities of these critical enzymes of physiological importance.

Topics: Alkaloids; Cardiovascular Diseases; Carotenoids; Chronic Disease; Diabetes Mellitus, Type 2; Dietary Supplements; Erectile Dysfunction; Flavonoids; Functional Food; Health Promotion; Humans; Lignans; Male; Neurodegenerative Diseases; Nutritional Requirements; Phenols; Polyphenols; Stilbenes

Phytoestrogens are polyphenols similar to human estrogens found in plants or derived from plant precursors. Phytoestrogens are found in high concentration in soya, flaxseed and other seeds, fruits, vegetables, cereals, tea, chocolate, etc. They comprise several classes of chemical compounds (stilbenes, coumestans, isoflavones, ellagitannins, and lignans) which are structurally similar to endogenous estrogens but which can have both estrogenic and antiestrogenic effects. Although epidemiological and experimental evidence indicates that intake of phytoestrogens in foods may be protective against certain chronic diseases, discrepancies have been observed between in vivo and in vitro experiments. The microbial transformations have not been reported so far in stilbenes and coumestans. However, isoflavones, ellagitanins, and lignans are metabolized by intestinal bacteria to produce equol, urolithins, and enterolignans, respectively. Equol, urolithin, and enterolignans are more bioavailable, and have more estrogenic/antiestrogenic and antioxidant activity than their precursors. Moreover, equol, urolithins and enterolignans have anti-inflammatory effects and induce antiproliferative and apoptosis-inducing activities. The transformation of isoflavones, ellagitanins, and lignans by intestinal microbiota is essential to be protective against certain chronic diseases, as cancer, cardiovascular disease, osteoporosis, and menopausal symptoms. Bioavailability, bioactivity, and health effects of dietary phytoestrogens are strongly determined by the intestinal bacteria of each individual.

Topics: Animals; Chocolate; Chronic Disease; Coumarins; Disease Models, Animal; Edible Grain; Flax; Fruit; Gastrointestinal Microbiome; Glycine max; Humans; Hydrolyzable Tannins; Intestines; Isoflavones; Lignans; Phytoestrogens; Polyphenols; Stilbenes; Tea; Vegetables

Lignans constitute a group of phytochemicals, which are produced by oxidative dimerization of two phenylpropanoid units. Furfuran type lignans such as secoisolariciresinol, matairesinol, lariciresinol or pinoresinol are widely distributed in edible plants, and most of those dietary lignans are metabolized by the gut microflora to enterolactone and enterodiol, also known as enterolignans, traditionally classified as phytoestrogens. The rich sources of lignans are flaxseed, sesame seeds, cereal products, and Brassica vegetables. There is a growing interest in biological functions of lignans from edible plants, since a higher intake of edible plants containing lignans is known to reduce the incidence of certain chronic diseases. This review deals with the isolation and preparation of furfuran type lignans from edible plants, and their bioactivities such as anticancer, antioxidant, cardiovasculoprotective, neuroprotective, and anti-inflammatory activities, so that recent informations about bioactive lignans from edible plants may be available for the development of potential functional food agents. In this article, patents based information is also discussed.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Chronic Disease; Functional Food; Lignans; Neuroprotective Agents; Plants, Edible

The purpose of the present study was to evaluate the antidepressant effect of deoxyschizandrin (DEO) in chronic unpredictable mild stress (CUMS)-induced mice. The mice were subjected to CUMS paradigm for 8 weeks. From the sixth week, the mice were intragastrically treated with DEO once daily for continuous 3 weeks. The behavior tests including sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST), and open field test were conducted. Additionally, the expressions of TLR4, MyD88, TRAF6, p-NF-κBp65, NLRP3, cleaved caspase-1, cleaved IL-1β, GluR, and PSD95 in hippocampus were detected by western blot. The concentrations of IL-6 and TNF-α in hippocampus were determined by enzyme linked immune sorbent assay (ELISA). The dendritic spine density was observed by Golgi-Cox staining. As a result, the treatment with DEO relieved anhedonia in SPT, and reduced immobile duration in FST and TST. DEO treatment effectively attenuated the CUMS-caused alterations of TLR4, MyD88, TRAF6, p-NF-κBp65, NLRP3, cleaved caspase-1, cleaved IL-1β, GluR, and PSD95. Furthermore, DEO could reduce the hippocampal inflammatory cytokine content and increase the density of dendritic spine. In conclusion, the present work indicated that DEO exhibited antidepressant effect on CUMS-induced depressive mice, which was possible due to the TLR4/NF-κB/NLRP3 pathway and the amelioration of dendritic spine density through GluR/PSD95 cascade.

Topics: Animals; Antidepressive Agents; Chronic Disease; Cyclooctanes; Depression; Disease Models, Animal; Gene Expression Regulation; Hippocampus; Lignans; Male; Mice; Polycyclic Compounds; Stress, Psychological

Honokiol (HNK), the main active component of Magnolia officinalis, has shown a variety of pharmacological activities. In the present study, we measured the antidepressant-like effects of HNK in a rat model of chronic unpredictable mild stress (CUMS) and explored its possible mechanisms. The antidepressant-like effects of HNK were assessed in rats by an open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Then, serum levels of corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) and hippocampal brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor α (GRα) levels were assessed to explore the possible mechanisms. We identified that HNK treatment (2, 4, and 8 mg/kg) alleviated the CUMS-induced behavioural deficits. Treatment with HNK also normalized the CUMS-induced hyperactivity of the limbic hypothalamic-pituitary-adrenal (HPA) axis, as indicated by reduced CRH, ACTH and CORT serum levels. In addition, HNK increased the expression of GRα (mRNA and protein) and BDNF (mRNA and protein) in the hippocampus. These data confirmed the antidepressant-like effects of HNK, which may be related to its normalizing the function of the HPA axis and increasing the BDNF level in the hippocampus.

Topics: Animals; Antidepressive Agents; Biphenyl Compounds; Brain-Derived Neurotrophic Factor; Chronic Disease; Dose-Response Relationship, Drug; Hippocampus; Hypothalamo-Hypophyseal System; Lignans; Male; Pituitary-Adrenal System; Rats; Rats, Wistar; Stress, Psychological; Treatment Outcome

This study investigated the effects of (-)-sesamin on chronic electric footshock (EF) stress-induced anxiety disorders in mice. Mice were treated with (-)-sesamin (25 and 50 mg/kg) orally once a day for 21 days prior to exposure to EF stress (0.6 mA, 1 s every 5 s, 3 min). Mice treated with (-)-sesamin (25 and 50 mg/kg) exhibited less severe decreases in the number of open arm entries and time spent on open arms in the elevated plus-maze test and the distance traveled in the open field test following exposure to chronic EF stress. Similarly, mice treated with (-)-sesamin exhibited significantly less severe decreases in brain levels of dopamine, norepinephrine, and serotonin following exposure to chronic EF stress. Increases in serum levels of corticosterone and expression of c-Fos were also less pronounced in mice treated with (-)-sesamin (25 and 50 mg/kg). These results suggest that (-)-sesamin may protect against the effects of chronic EF stress-induced anxiety disorders by modulating dopamine, norepinephrine, and serotonin levels, c-Fos expression, and corticosterone levels.

Topics: Animals; Anti-Anxiety Agents; Antioxidants; Anxiety Disorders; Biogenic Monoamines; Brain; Chronic Disease; Corticosterone; Dioxoles; Lignans; Male; Mice; Mice, Inbred ICR; Stress, Psychological; Treatment Outcome

Chronic inflammation has been implicated in the etiology of various chronic diseases. We previously found that certain urinary isoflavones are associated with markers of inflammation. In the present study, we examined the associations of serum C-reactive protein (CRP) and white blood cell (WBC) count with lignans, which are more frequent in the Western diet than isoflavones.. Our analysis included 2,028 participants of NHANES 2005-2008 and 2,628 participants of NHANES 1999-2004 aged 18 years and older. The exposures of interest were urinary mammalian lignans (enterodiol and enterolactone). Outcome variables were two inflammatory markers (CRP [≤10 mg/L] and WBC [≥3.0 and ≤11.7 (1,000 cells/μL)]). Log-transformed CRP concentration and WBC count by log-transformed creatinine-standardized concentrations of mammalian lignans were used for linear regression.. Statistically significant inverse associations of urinary lignan, enterodiol, and enterolactone concentrations with circulating CRP and WBC counts were observed in the multivariate-adjusted models: In NHANES 2005-2008, per one-percent increase in lignan concentrations in the urine, CRP concentrations and WBC counts decreased by 8.1 % (95 % CI -11.5, -4.5) and 1.9 % (95 % CI -2.7; -1.2), respectively. Per one-percent increase in enterodiol and enterolactone, WBC counts decreased by 2.1 % (95 % CI -2.8, -1.3) and 1.3 % (95 % CI -1.9, -0.6), respectively. In NHANES 1999-2004, analogous results were 3.0 % (95 % CI -5.6, -0.3), 1.2 % (95 % CI -2.0; -0.4), 1.0 % (95 % CI -1.8, -0.2), and 0.8 % (95 % CI -1.4, 0.2).. Mammalian lignans were inversely associated with markers of chronic inflammation. Due to the cross-sectional design, our findings require confirmation in prospective studies.

Topics: 4-Butyrolactone; Adult; Aged; Biomarkers; C-Reactive Protein; Chronic Disease; Cross-Sectional Studies; Female; Humans; Inflammation; Leukocyte Count; Lignans; Male; Middle Aged; Nutrition Surveys; United States

Classical Chinese pharmacopeias describe numerous excellent herbal formulations, and each prescription is an outstanding pool of effective compounds for drug discovery. Clarifying the bioactivity of the combined mechanisms of the ingredients in complex traditional Chinese medicine formulas is challenging. A classical formula known as Qingfei Xiaoyan Wan, used clinically as a treatment for prevalent chronic lung disease, was investigated in this work. A mutually enhanced bioactivity-guided ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) characterization system was proposed, coupled with a dual-luciferase reporter assay for β2AR-agonist cofactor screening. Arctiin, arctigenin, descurainoside and descurainolide B, four lignin compounds that showed synergistic bronchodilation effects with ephedrine, were revealed. The synergistic mechanism of arctigenin with the β2ARagonist involved with the reduction of free Ca2+ was clarified by a dual-luciferase reporter assay for intracellular calcium and the Ca2+ indicator fluo-4/AM to monitor changes in the fluorescence. The relaxant and contractile responses of airway smooth muscle are regulated by crosstalk between the intracellular cAMP and calcium signaling pathways. Our data indicated the non-selective βAR agonist ephedrine as the principal bronchodilator of the formula, whereas the lignin ingredients served as adjuvant ingredients. A greater understanding of the mechanisms governing the control of these pathways, based on conventional wisdom, could lead to the identification of novel therapeutic targets or new agents for the treatment of asthma and COPD.

Topics: Adrenergic beta-2 Receptor Agonists; Animals; Asthma; Bronchodilator Agents; Calcium; Cell Line; Chromatography, High Pressure Liquid; Chronic Disease; Disease Models, Animal; Drug Synergism; Drugs, Chinese Herbal; Ephedrine; Flavonoids; Furans; Glucosides; Guinea Pigs; Humans; Lactones; Lignans; Lung Diseases; Medicine, Chinese Traditional; Myocytes, Smooth Muscle; Trachea

The reduction of parasitism tissue upon treatment with two lignano lactones, namely (-)- cubebin (CUB) and (-)-hinokinin (HNK), was evaluated in the chronic phase of Chagas' disease by quantifying the enzyme beta-galactosidase expressed by the CL B5 clone strain of Trypanosoma cruzi. Tissue karyometry was also performed. Treatment with the assessed lignans led to a larger reduction in parasitism tissue in all evaluated organs, compared with benznidazole (BZN). Oral treatment with CUB or HNK was more effective. Karyometry results demonstrated that the infected control animals had increased nuclear area compared with uninfected controls, indicating cellular hypertrophy. Results also revealed that use of CUB or HNK was able to significantly prevent this increase, and a slight decrease in the nuclear area was observed, compared with mice treated with BZN. Taken together, these data demonstrate that CUB and HNK could be considered as potential compounds for the development of new drugs for treatment of Chagas' disease.

Topics: 4-Butyrolactone; Animals; Benzodioxoles; beta-Galactosidase; Chagas Disease; Chronic Disease; Dioxoles; Heart; Karyometry; Lactones; Lignans; Liver; Mice; Mice, Inbred BALB C; Spleen; Treatment Outcome; Trypanocidal Agents; Trypanosoma cruzi

The aim of this study was to investigate the synergistic hepatoprotective effect of lignans from Fructus Schisandrae chinensis (LFS) with Astragalus polysaccharides (APS) on chronic liver injury in male Sprague-Dawley rats. Subcutaneous injection of 10% CCl(4) twice a week for 3 months resulted in significantly (p<0.001) elevated serum alanine aminotransferase (ALT), asparate aminotransferase (AST), alkaline phosphatase (ALP) activities compared to controls. In the liver, significantly elevated levels (p<0.001) of malondialdehyde (MDA), lowered levels of reduced glutathione (GSH) (p<0.05) and catalase (CAT) (p<0.001), superoxide dismutase (SOD) (p<0.01)were observed following CCl(4) administration. 'LFS+ASP' treatment of rats at doses of 'LFS (45mg/kg)+APS (150mg/kg)' and 'LFS (135mg/kg)+APS (450mg/kg)' displayed hepatoprotective and antioxidative effects than the administration of either LFS or APS, as evident by lower (p<0.005 or 0.001) levels of serum ALT, AST, ALP and hepatic MDA (p<0.001) concentration, as well as higher SOD (p<0.05 or 0.005), CAT activities(p<0.01 or 0.005), GSH concentration (p<0.05 or 0.005) compared to the toxin treated group. Histopathological examinations revealed severe fatty degeneration in the toxin group, and mild damage in groups treated with 'LFS+APS' were observed. The coefficients drug interaction (CDI) between each individual drug and their combination (at the same dose of their single treatment) of these foregoing parameters were all less than 1, indicating that LFS and APS display hepatoprotective and antioxidant properties and act in a synergistic manner in CCl(4) induced liver injury in rats.

Topics: Animals; Astragalus propinquus; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Chronic Disease; Drug Synergism; Drug Therapy, Combination; Enzymes; Fatty Liver; Fruit; Lignans; Liver; Male; Malondialdehyde; Phytotherapy; Plant Extracts; Plant Roots; Polysaccharides; Protective Agents; Rats; Rats, Sprague-Dawley; Schisandra

The lignan enterolactone, a phytoestrogen, may protect against hormone-dependent cancers and cardiovascular diseases. It is produced by the intestinal microflora from dietary precursors. Because of the pronounced impact of antimicrobials on the intestinal microflora, the authors examined whether serum enterolactone concentration is affected by previous use of oral antimicrobials. Enterolactone was measured by time-resolved fluoroimmunoassay in 2,753 Finnish men and women aged 25--64 years who participated in a cross-sectional national survey in 1997. Background information was collected by self-administered questionnaire, and data on antimicrobial treatment were gathered from the nationwide prescription database of the Social Insurance Institution. Serum enterolactone concentration was significantly lower in those who had used oral antimicrobials up to 12--16 months before serum sampling than in nonusers (16.4 vs. 19.3 nmol/liter). The concentration was associated with the number of treatments and the time from the last treatment. Modest differences were present between various antimicrobials. The authors' findings support the crucial role of gut microflora in the metabolism of lignans. Furthermore, recent use of antimicrobials should be considered when the association between serum enterolactone concentration and risk of chronic diseases is studied.

Topics: 4-Butyrolactone; Administration, Oral; Adult; Anti-Bacterial Agents; Biomarkers; Chronic Disease; Cross-Sectional Studies; Digestive System; Female; Humans; Lignans; Middle Aged; Risk Factors