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Chemical composition of flaxseed. (a) Schematic representation of the lignan macromolecule. The principal flaxseed lignan, secoisolariciresinol diglucoside (SDG), exists as a macromolecule in the flaxseed hull. This polymer complex is composed of five SDG structures held together by four hydroxy-methylglutaric acid (HMGA) residues with the hydroxycinnamic acids, p-coumaric glucoside (4-O-β-d-glucopyranosyl-p-coumaric acid or linocinnamarin) (CouAG), and ferulic acid glucoside (4-O-β-d-glucopyranosyl ferulic acid) (FeAG) as end units linked to the glucosyl moiety of SDG. The backbone moieties of this macromolecule are represented by the circles. The overlapping circles represent the linker molecule HMGA and the squares represent the terminal units. The terminal unit can be CouAG/FeAG or HMGA. (b) Postulated structure of the lignan oligomer. The SDG-HMGA polymer complex is converted into its monomer units-3-HMGA and SDG-by hydrolysis (average size, n = 3). Flaxseed contains high levels of the lignan oligomer (with ester linkages to HMGA, cinnamic acid, and other phenolic glucosides), which undergoes conversion to its aglycone, secoisolariciresinol (SECO), with further biotransformation into mammalian lignans by the action of the colonic bacteria in mammalian systems. Adopted from references
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Cancer causes considerable morbidity and mortality across the world. Socioeconomic, environmental, and lifestyle factors contribute to the increasing cancer prevalence, bespeaking a need for effective prevention and treatment strategies. Phytochemicals like plant polyphenols are generally considered to have anticancer, anti-inflammatory, antiviral,...
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Context 1
... polymer complex is composed of five SDG structures held together by four hydroxy-methylglutaric acid (HMGA) residues (3-hydroxy-3-methyl glutaric acid [371]) with the hydroxycinnamic acids, p-coumaric glucoside (4-O-β-d-glucopyranosyl-p-coumaric acid or linocinnamarin [371]), and ferulic acid glucoside (4-O-β-d-glucopyranosyl ferulic acid [371]) as end units linked to the glucosyl moiety of SDG [354,372,[374][375][376]. HMGA is considered the backbone of the lignan macromolecule [374] (Figure 2). The flavonoid herbacetin diglucoside (HDG) is also part of the lignan macromolecule attached via ester linkages with HMGA, similar to SDG [374,377]. ...
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Prostate cancer (PCa) represents a major cause of cancer mortality among men in developed countries. Patients with recurrent disease initially respond to androgen-deprivation therapy, but the tumor eventually progresses into castration-resistant PCa; in this condition, tumor cells acquire the ability to escape cell death and develop resistance to c...
Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death in adult women worldwide. Over 85% of BC cases are non-hereditary, caused by modifiable extrinsic factors related to lifestyle, including dietary habits, which play a crucial role in cancer prevention. Although many epidemiological and observational studi...
Citations
... Lignans present in Linum usitatissimum L. include the stereospecific compounds (+)-pinoresinol and (−)-pinoresinol, (+)-lariciresinol and (−)-lariciresinol, and (+)-secoisolariciresinol and (−)-secoisolariciresinol. The biosynthetic pathway of these lignans can continue through the synthesis of (−)-yatein, (−)-podophyllotoxin, or (−)-hinokinin (Marcotullio et al. 2014;Corbin et al. 2017;De Silva et al. 2019). The most common form of (+)-secoisolariciresinol in seeds is its diglucosidic form, known as (+)-secoisolariciresinol diglucoside, while (−)-matairesinol is predominantly found in the aerial parts (Corbin et al. 2017;Markulin et al. 2019;Prasad et al. 2020). ...
Flaxseed (Linum usitatissimum L.) is renowned for having the highest concentration of lignans among all plant species worldwide. However, it also contains a notable amount of cyanogenic glycosides, prompting efforts to reduce their levels. MicroRNAs, recognized as significant epigenetic factors, hold the potential to serve as genetic markers in achieving this breeding goal. In this study, 44,885 mature microRNAs were utilized alongside one genome and four transcriptomes of flax. Twelve gene sequences were obtained for five lignan enzymes and three enzymes related to cyanogenic glycosides. Based on our in silico approach, we identified 15 microRNA families for the lignan metabolic pathway, 10 for the cyanogenic glycoside pathway, and 6 regulating both pathways. Additionally, we contributed to the annotation of the used transcriptomes and verified the functionality of the “Finding genes by keyword” algorithm available on Phytozome 13. The results obtained led to the design of a unique schema for microRNA mediated regulation in the biosynthetic pathways of lignans and cyanogenic glycosides. This research will enhance our understanding of the regulatory mechanisms of microRNA in these biosynthetic pathways, along with other specialized metabolites. The predicted microRNAs can be employed in marker-assisted selection with the breeding objective of optimizing the ratio of nutritional and antinutritional components in flaxseed while maintaining current physiological parameters.
... As a lignan exclusively found in EVOO, 1-AP can be used as a marker to authenticate EVOO and to distinguish EVOOs from different cultivars or geographical locations. The authentication of EVOO by using 1-AP has been studied by several authors [43,58,80,81]. ...
Extra virgin olive oil (EVOO) is a symbol of the Mediterranean diet, constituting its primary source of fat. The beneficial effect of EVOO is strictly related to the presence of fatty acids and polyphenols, bioactive compounds endowed with nutraceutical properties. Among EVOO polyphenols, lignans possess a steroid-like chemical structure and are part of the phytoestrogen family, which is renowned for its health properties. The natural lignans (+)-pinoresinol and 1-acetoxypinoresinol (1-AP) are commonly present in olives and in EVOO. Although (+)-pinoresinol is found in different edible plants, such as flaxseed, beans, whole-grain cereals, sesame seeds, and certain vegetables and fruit, 1-AP was exclusively identified in olives in 2000. So far, the scientific literature has extensively covered different aspects of (+)-pinoresinol, including its isolation and nutraceutical properties. In contrast, less is known about the olive lignan 1-AP. Therefore, this review aimed to comprehensively evaluate the more important aspects of 1-AP, collecting all the literature from 2016 to the present, exploring its distribution in different cultivars, analytical isolation and purification, and nutraceutical properties.
... Lignans exhibit promising anticancer effects by modulating multiple targets of carcinogenesis. Additionally, they possess anti-inflammatory, antiviral, and antimicrobial properties, suggesting potential benefits in cancer prevention [101]. ...
The evolution of wheat bread as a dietary staple underscores its essential role in providing energy, protein, fiber, and vital nutrients. To address contemporary health challenges such as type 2 diabetes and cardiovascular diseases, fortifying wheat bread with health-promoting additives becomes imperative to mitigate deficiencies resulting from refined wheat flour consumption. Functional food innovations, aligned with sustainability goals and circular economy principles, offer promising approaches for addressing these concerns. Integrating by-products from fruits and oil crops into bread formulations enhances health benefits by boosting dietary fiber, bioactive compounds, and antioxidant potential. However, gaps persist in understanding anti-nutritional substances and contaminants in final products, necessitating further research for comprehensive safety assessments. The addition of by-product raw materials significantly influences dough rheology and sensory characteristics, potentially achieving quality comparable to traditional wheat bread. Challenges include inconsistencies in bread and by-product specifications across studies, hindering direct result comparison. Overcoming these obstacles is crucial for maximizing the potential of agri-food by-products in creating healthier, sustainable bread options while maintaining safety and quality standards.
... The flaxseed lignin, secoisolariciresinol diglucoside, enterolactone, and enterodiol exert antioxidant activity against DNA damage and lipid peroxidation and, therefore, were found to be beneficial in cancer, hypercholesterolemia, hyperglycemia, atherosclerosis, and lupus nephritis. In preclinical anticancer models, lignans reduced growth, progression, and angiogenesis [349]. Further, neolignan, isolariciresinol, and isolariciresinol isolated from German Riesling wine were reported to show antioxidant activity [350]. ...
Polyphenols, as secondary metabolites ubiquitous in plant sources, have emerged as pivotal bioactive compounds with far-reaching implications for human health. Plant polyphenols exhibit direct or indirect associations with biomolecules capable of modulating diverse physiological pathways. Due to their inherent abundance and structural diversity, polyphenols have garnered substantial attention from both the scientific and clinical communities. The review begins by providing an in-depth analysis of the chemical intricacies of polyphenols, shedding light on their structural diversity and the implications of such diversity on their biological activities. Subsequently, an exploration of the dietary origins of polyphenols elucidates the natural plant-based sources that contribute to their global availability. The discussion extends to the bioavailability and metabolism of polyphenols within the human body, unraveling the complex journey from ingestion to systemic effects. A central focus of the review is dedicated to unravelling the antioxidant effects of polyphenols, highlighting their role in combating oxidative stress and associated health conditions. The comprehensive analysis encompasses their impact on diverse health concerns such as hypertension, allergies, aging, and chronic diseases like heart stroke and diabetes. Insights into the global beneficial effects of polyphenols further underscore their potential as preventive and therapeutic agents. This review article critically examines the multifaceted aspects of dietary polyphenols, encompassing their chemistry, dietary origins, bioavailability/metabolism dynamics, and profound antioxidant effects. The synthesis of information presented herein aims to provide a valuable resource for researchers, clinicians, and health enthusiasts, fostering a deeper understanding of the intricate relationship between polyphenols and human health.
... 28 Several laboratories have demonstrated the effects of lignans from flaxseed, which contain SDG, for improving human health as well as for cancer prevention or treatment. 20,29 Previously, we used dietary SDG to successfully control malignant diseases. 30 Since the elderly patient we reported here was not eligible for surgery or chemo-or radiotherapy, we treated her with dietary SDG as the only therapy and the patient has had progression-free survival of one year. ...
Introduction
Pancreatic cancer (PC) is among the deadliest malignancies. Kidney cancer (KC) is a common malignancy globally. Chemo- or radio-therapies are not very effective to control PC or KC, and overdoses often cause severe site reactions to the patients. As a result, novel treatment strategies with high efficacy but without toxic side effects are urgently desired. Secoisolariciresinol diglucoside (SDG) belongs to plant lignans with potential anticancer activities, but clinical evidence is not available in PC or KC treatment.
Patient Concerns
We report a rare case of an 83-year-old female patient with pancreatic and kidney occupying lesions that lacked the conditions to receive surgery or chemo- or radiotherapy.
Diagnosis
Pancreatic and kidney cancers.
Interventions
We gave dietary SDG to the patient as the only therapeutics.
Outcomes
SDG effectively halted progression of both PC and KC. All clinical manifestations, including bad insomnia, loss of appetite, stomach symptoms, and skin itching over the whole body, all disappeared. The initial massive macroscopic hematuria became microscopic and infrequent, and other laboratory results also gradually returned to normal. Most of the cancer biomarkers, initially high such as CEA, CA199, CA724, CA125, came down rapidly, among which CA199 changed most radically. This patient has had progression-free survival of one year so far.
Conclusion
These results demonstrate the potent inhibitory effects of SDG on PC and KC of this patient and provide promising novel therapeutics for refractory malignant tumors.
... 6 Secoisolariciresinol diglucoside (SDG), the main lignan in flaxseed, is poorly absorbed because of its polarity. 7 Instead, SDG consumed is hydrolyzed by intestinal microflora to SECO, which further undergoes absorption, metabolism or biotransformation to enterolignans, enterodiol (END) and enterolactone (ENL). 8 Tiny SECO, END and ENL fractions are absorbed intact into the systemic circulation. ...
... At the same time, most of them are primarily found as glucuronic acid or sulfate conjugates as a result of extensive first-pass metabolism by intestinal and hepatic phase II enzymes. 7,8 However, substantial interindividual variation has been reported regarding enterolignan production because of differences in the gut microbial community across individuals. In vitro, biotransformation of flax lignan could be an effective strategy for preparing flax lignan functional ingredients with higher bioavailability and bioactivity. ...
BACKGROUND
Flax lignan has attracted much attention because of its potential bioactivities. However, the bioavailability of secoisolariciresinol diglucoside (SDG), the main lignan in flaxseed, depends on the bioconversion by the colon bacteria. Lactic acid bacteria (LAB) with β‐glucosidase activity has found wide application in preparing bioactive aglycone.
RESULTS
LAB strains with good β‐glucosidase activity were isolated from fermented tofu. Their bioconversion of flax lignan extract was investigated by resting cell catalysis and microbial fermentation, and the metabolism of SDG by Lactiplantibacillus plantarum C5 following fermentation was characterized by widely targeted metabolomics. Five L. plantarum strains producing β‐glucosidase with broad substrate specificity were isolated and identified, and they all can transform SDG into secoisolariciresinol (SECO). L. plantarum C5 resting cell reached a maximum SDG conversion of 49.19 ± 3.75%, and SECO generation of 21.49 ± 1.32% (0.215 ± 0.013 mm) at an SDG substrate concentration of 1 mM and 0.477 ± 0.003 mm SECO was produced at 4 mm within 24 h. Although sixteen flax lignan metabolites were identified following the fermentation of SDG extract by L. plantarum C5, among them, four were produced following the fermentation: SECO, demethyl‐SECO, demethyl‐dehydroxy‐SECO and isolariciresinol. Moreover, seven lignans increased significantly.
CONCLUSION
Fermentation significantly increased the profile and level of flax lignan metabolites, and the resting cell catalysis benefits from higher bioconversion efficiency and more straightforward product separation. Resting cell catalysis and microbial fermentation of flax lignan extract by the isolated β‐glucosidase production L. plantarum could be potentially applied in preparing flax lignan ingredients and fermented flaxseed. © 2024 Society of Chemical Industry.
... Recently, medicinal plants and plant-derived compounds have attracted worldwide attention in the treatment of various liver diseases [19]. Flaxseed lignan, termed lignan macromolecule, is mainly composed of SDG structures held together by four hydroxymethylglutaric acid (HMGA) residues [20]. It can be converted into active enteroligan, Furthermore, Spearman correlation analysis was performed to examine the relationship between altered metabolites and the changed biochemical parameters (Supplemental File Figure S2). ...
... Recently, medicinal plants and plant-derived compounds have attracted worldwide attention in the treatment of various liver diseases [19]. Flaxseed lignan, termed lignan macromolecule, is mainly composed of SDG structures held together by four hydroxymethylglutaric acid (HMGA) residues [20]. It can be converted into active enteroligan, such as END and ENL by flaxseed lignan-deglycosolating bacteria, which are characterized by various biological activities, including activation of tissue-specific estrogen receptors and anticancer and anti-inflammatory effects [21]. ...
This study examined the protective effect of flaxseed lignans on liver damage caused by an overdose of paracetamol (PAM). The findings demonstrated that administering 800 mg/kg/d flaxseed lignan prior to PAM significantly decreased the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBi) levels, while it increased liver superoxide dismutase (SOD) and glutathione (GSH) levels in mice. Flaxseed lignan renovated the gut microbiota dysbiosis induced by PAM by promoting the proliferation of sulfonolipid (SL) producing bacteria such as Alistipes and lignan-deglycosolating bacteria such as Ruminococcus while inhibiting the growth of opportunistic pathogen bacteria such as Acinetobacter and Clostridium. Furthermore, flaxseed lignan modulated the serum metabolomic profile after PAM administration, specifically in the taurine and hypotaurine metabolism, phenylalanine metabolism, and pyrimidine metabolism. The study identified eight potential biomarkers, including enterolactone, cervonyl carnitine, acutilobin, and PC (20:3(5Z, 8Z, 11Z)/20:0). Overall, the results suggest that flaxseed lignan can alleviate PAM-induced hepatotoxicity and may be beneficial in preventing drug-induced microbiome and metabolomic disorders.
... They are also precursors for gut microbiota-derived mammalian phytoestrogens enterolignans (enterodiol and enterolactone), possessing mainly antiinflammatory and apoptotic activities [13]. The content of lignans in linseed is extraordinary and ranges between 9 and 30 mg per gram of seed, which is 95-800 times over other plant sources, followed by sesame seeds and rye bran [14]. SDG content can vary according to the genotype of linseed and environment, while the effect of cultivar is appointed to be more significant in the relevant studies [15][16][17]. ...
Linseed represents a rich source of nutritional, functional and health-beneficial compounds. Nevertheless, the chemical composition and content of bioactive compounds may be quite variable and potentially affected by various factors, including genotype and the environment. In this study, the proximate chemical composition, lignans content and antioxidant potential of six experimentally grown linseed cultivars were assessed and compared. A diagonal cultivation trial in the University of South Bohemia Experimental Station in České Budějovice, Czech Republic, was established in three subsequent growing seasons (2018, 2019 and 2020). The results showed that the cultivar and growing conditions influenced most studied parameters. The lack of precipitation in May and June 2019 negatively affected the seed yield and the level of secoisolariciresinol diglucoside but did not decrease the crude protein content, which was negatively related to the oil content. The newly developed method for lignans analysis allowed the identification and quantification of secoisolariciresinol diglucoside and matairesinol. Their content correlated positively with the total polyphenol content and antioxidant assays (DPPH and ABTS radical scavenging activity), indicating the significant contribution to the biofunctional properties of linseed. On the other hand, we did not detect minor linseed lignans, pinoresinol and lariciresinol. The results of this study showed the importance of cultivar and growing conditions factors on the linseed chemical composition and the lignans content, determining its nutritional and medicinal properties.
... Flaxseed, a fundamental agricultural and industrial raw material produced for human consumption, contains high levels of bioactive compounds such as lignan and vitamins [1]. It serves not only as a major food resource but also as an important bioreactor for the production and storage of phytochemicals [2][3][4]. As a nutritional resource, flax possesses a beneficial chemical composition in oil, characterized by abundant unsaturated fatty acids, soluble fiber, protein, lignan, vitamins, carotenoid, and antioxidants ( Figure S1) [5]. ...
Multiple varieties of flaxseeds have been identified in the world, yet the relationship between these varieties, their agronomic traits, and their seeds’ quality remains unclear. This study aimed to determine the level of lignan, vitamins and carotenoids in 40 selected flaxseed varieties, and the relationship between varieties, agronomic traits, and seed quality was investigated. In this study, notably, fiber flax variety No. 225 exhibited the highest lignan content among all tested seeds. Additionally, oil variety No. 167 demonstrated the highest level of α-tocotrienol (α-T3), β-tocopherol (β-T), γ-tocotrienol (γ-T3), and β-carotene (β-Car.). Conversely, intermediate flax variety No. 16 displayed the highest content of α-tocopherol (α-T), but lowest content of lutein (Lut.), zeaxanthin (Zea.), β-carotene (β-Car.), and total carotenoids (Total Car.). Furthermore, a correlation was observed between petal color with the lignan, while a strong correlation has been explored in seed yield, seed type, plant natural height, and fiber content in straw. Nevertheless, further investigation is required to elucidate the internal relationship between varieties with compositions.
... The flax plant has been cultivated for seed and fiber production since ancient times [24]. The seeds have numerous health benefits based on their high content of α-linolenic acid, lignans, proteins, fats, vitamins, minerals, α-tocopherol (vitamin E), ascorbic acid (vitamin C), carotene, and B-group vitamins (thiamine, B1, and riboflavin, B2) [25,26]. α-Linolenic acid has been beneficial in metabolic syndrome, cancer, inflammation, obesity, neuropathy, and regulation of intestinal flora [27]. ...
Flax seeds stored in unfavorable conditions were exposed to static magnetic fields (SMFs) of 50–350 mT for 20–120 min to overcome low germination and quality. Seed germination increased slightly with increasing strength of SMF and duration of treatment. Seed germination from 89% to 100% was achieved in SMF treatments of 150 mT (120 min), 200 mT (80–120 mT), 250 mT (60–120 min), 300 mT (40–120 min), and 350 mT (40–120 min). In these treatments, germination was 2.78- to 3.12-fold higher than in the control after 10 days. Treatments with 350 mT for 100 and 120 min showed the best results in germination (100%), as well as a 26.81-fold increase in vigor I, 28.69-fold increase in vigor II, 1-fold increase in chlorophyll a, 0.84-fold in chlorophyll b, 0.46-fold increase in carotenoid content, and 2.63-fold increase in catalase activity compared to the control after 10 days. Also, SMF treatment of 350 mT (20–120 min) reduced cell leakage and electrical conductivity by 1-fold compared to the control. SMF is a healthy, biologically safe, and environmentally friendly treatment and can be a tool for overcoming problems of low germination and quality of seeds stored under unfavorable conditions.
