Secoisolariciresinol Diglycoside Research Articles

A review on flaxseeds: Nutritional profile, health benefits, value added products, and toxicity

AbstractFlaxseed has been consumed by people for a very long time due to its nutritional value and medicinal applications. In India, flaxseed is used for both culinary and medicinal reasons. About 45% of alpha‐linolenic acid (ALA), 28%–30% protein, and 35% fiber are present in flaxseeds. The finest source of omega‐3 fatty acids for those who do not consume seafood is flaxseed. Flaxseeds have lignin, of which primary lignan is secoisolariciresinol diglycoside, with low amounts of isolariciresinol, lariciresinol, pinoresinol, and matairesinol. Flaxseed is probably safe for most grown‐ups. The daily number of bowel movements may increase if flaxseed is included in the diet. Additionally, it may result in side effects such as gas, bloating, stomach pain, and nausea. Higher dosages are probably going to cause more secondary effects. Due to the nutritional profile of flaxseeds, they exhibit various health benefits which include; improving cardiac health, improving brain development, improving skin health, improving gut health, maintaining blood sugar level, reducing the risk of renal diseases, and several types of cancers. The purpose of this study is to provide a general overview of the nutritional profile, health benefits, value‐added products, and toxicity of flaxseeds.

Dose-Dependent Production of Mammalian Lignans in Rats and In Vitro from the Purified Precursor Secoisolariciresinol Diglycoside in Flaxseed

The mammalian lignans enterodiol (ED) and enterolactone (EL) produced from colonic bacterial action on dietary precursors have exhibited anticarcinogenic effects in vitro. The major lignan precursor in flaxseed (a rich source) has been identified as secoisolariciresinol diglycoside (SDG). The purpose of this study was to first isolate SDG and determine whether 1) SDG accounted for all the lignan production from flaxseed; 2) this production was dose-related; and 3) a relationship between in vitro production and in vivo urinary excretion existed. Extraction of flaxseed with dioxane:ethanol (1:1, v/v) followed by chromatographic separations yielded the purified SDG. Rats were fed a high fat diet without/with 2.5, 5 or 10 g/100g ground flaxseed or 1.1, 2.2 or 4.4 µmol SDG/d (equivalent to levels in the respective flaxseed diets) for 4 wk. In vitro lignan production was assessed by fermenting flaxseed or SDG for 24 h with human fecal inoculum. Urinary lignan excretion increased linearly with doses from 0–5% flaxseed and 0–2.2 µmol SDG/d followed by a plateau, indicating a threshold response. When all doses were considered, a curvilinear relationship was observed. A similar trend was seen in vitro for SDG, resulting in a high correlation between in vitro production and in vivo excretion of lignans (r = 0.990, P < 0.02). Thus in vivo response can be predicted with confidence based on in vitro results. Theoretical urinary ED + EL from the SDG present in flaxseed correlated with the actual excretion in flaxseed-fed animals (r = 0.655, P < 0.005). However, urinary ED + EL of SDG-fed rats was only 20% of levels of flaxseed-fed rats, indicating the presence of other precursors or incomplete conversion of SDG to ED and EL.

Secoisolariciresinol diglucoside-derived metabolite, enterolactone, attenuates atopic dermatitis by suppressing Th2 immune response

Atopic dermatitis (AD) is a severe inflammatory skin disease caused by a combination of genetic, immune, and environmental factors. Intestinal microbiome disorders and changes in the immune microenvironment are associated with AD. We observed that gut bacterial metabolite enterolactone (ENL) was significantly reduced in AD model mice. Notably, patients with early childhood-onset AD exhibited decreased sera ENL level compared to the healthy controls, and the ENL level was negatively correlated with the SCORAD index. Secoisolariciresinol-diglycoside (SDG) is a natural dietary lignan of flaxseeds that can be converted by intestinal bacteria to ENL. Repeated applications of 2,4-dinitrochlorobenzene (DNCB) were performed on the ear and dorsal skin of mice to induce AD-like symptoms and skin lesions. Oral administration of SDG significantly decreased serum IgE levels and limited skin inflammation in the DNCB-induced AD mice. In addition, SDG treatment strongly limited the Th2 responses in AD mice. Moreover, we demonstrated that the IL-4 production was significantly suppressed by ENL under Th2 polarization conditions via the JAK-STAT6 signaling pathway in a concentration-dependent manner. We concluded that SDG and its derived metabolite ENL ameliorated AD development by reducing the Th2 immune response. These results suggested that SDG and ENL might be exploited as potential therapeutic candidates for AD treatment.

Secoisolariciresinol diglycoside (SDG) lignan content of oil flax: Genotypic and environmental variations and association with other traits

The secoisolariciresinol diglycoside (SDG) lignan of oil flax (Linum usitatissimum L.) is influenced by genotype, environment and the interaction of genotype ​× ​environment. This field study was conducted to investigate the effects of genotype and environment on the SDG lignan content, six genotypes (Longya 8, Zhangya 2, Linxiabai, Shandanbai, Gaolanbai, and DYMS) were sown under eight locations (Hohhot, Datong, Minle, Yili, Shuangta, Jingtai, Guyuan, and Zhangjiakou) in 2014 and 2015 in China. The experimental design was a randomized complete block with three replications. Results showed that Longya 8 had the highest SDG lignan content (7.27 ​mg/g) and Shandanbai had the lowest (4.71 ​mg/g) across 16 environments. The SDG lignan content ranged from 4.70 ​mg/g at Datong to 7.74 ​mg/g at Minle Research Station. In the present study, the results indicated that differences among genotypes in SDG lignan content accounted for 51.38% variation of the total variation and environments accounted for 44.40% variation of the total variation. Moreover, we found that the altitude had a positive effect on SDG lignan content of flaxseed, presumably owing to differences in temperature, humidity, sunshine time, etc. These results indicated that the SDG lignan content was genetically controlled, and was also to be influenced by environmental conditions, especially altitude.

Evaluation of the Antioxidant and Antiradical Properties of Some Phyto and Mammalian Lignans

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.

Flax Seed

Flax sed also known as flax oil and linseed oil, is derived from the seeds of the plant Linium usitatissimum. Flax seed oil is a very rich source of alpha-linolenic acid. Alpha-linolenic acid concentration in flaxseed oil ranges from approximately 40 to 60%.lower amounts of linoleic acid and oleic acid (each about 15%) are also present in flaxseed oil.ın addition, flaxseed contains varying amounts of the lignan, secoisolariciresinol diglycoside (SDG).

The legitimacy of using dietary supplement diglycoside secoisolariciresinol (SDG) from flaxseed in cancer.

Linseed, commonly known as flaxseed, is a fibre-rich food product. According to the recent study prepared by the American Institute for Cancer Research (AICR), an adequate intake of dietary fiber contributes to reducing the risk of colorectal cancer. In addition, the flaxseed and the oil extracted from it are considered to be food products with a high content of anti-inflammatory, unsaturated α-linolenic acid (ALA). However, the authors of the most recent scientific research have assigned the anticancer significance of flax seeds to plant lignan - secoisolariciresinol diglycoside (SDG), of which flaxseed is the main food source. This article provides a review of the world scientific literature together with an assessment of the validity of dietary supplementation with SDG from flaxseeds in cancer and during chemotherapeutic treatment. The paper also presents the European Food Safety Authority (EFSA) and the US Food and Drug Administration (FDA) view on dietary supplementation with flax seeds and its lignans. Additionally, selected dietary supplements available on the Polish market containing SDGs, linseed oil or linseed were analysed, together with a description of their intended use suggested by the manufacturers.

Abstract 1120: Randomized clinical trial of a flaxseed lignan in pre-menopausal women at high risk for development of breast cancer

Abstract Breast cancer prevention strategies for young pre-menopausal women must have minimal side effects and accommodate potential future child-bearing. Based on epidemiologic evidence and informed by a single-arm pilot study, we conducted a multi-institutional, placebo-controlled Phase IIB trial of the lignan secoisolariciresinol diglycoside (SDG) found in high concentrations in flaxseed. Benign breast tissue was acquired by random periareolar fine needle aspiration (RPFNA) from pre-menopausal women at increased risk for breast cancer during the follicular phase as estimated by dates. Those with cytologic hyperplasia and ≥2% positive cells by Ki-67 immunocytochemistry were eligible for randomization 2:1 to daily Brevail® (50 mg SDG) or placebo. After 12 months, RPFNA and blood for hormone assays were repeated. The primary endpoint was difference in change in Ki-67 between the randomization groups. A planned accrual of 230 was to provide an 80% power of detecting a 2.5% reduction in Ki-67 for the SDG group vs no reduction in the placebo group. Accrual was slower than anticipated and the study was closed with 180 enrollees at five sites. 152 (51 placebo, 101 SDG) sets of paired specimens were evaluable for the primary endpoint. Baseline Ki-67 was a median of 4.1% (range, 2.0 - 26.8%), with no difference between arms (Mann-Whitney nonparametric test, p=0.34). Both arms showed a decrease in percent Ki-67 over time (Wilcoxon signed rank test; p=0.034 for placebo, p=0.001 for SDG). Although Ki-67 reduction was greater in the SDG arm (median of -1.8% vs -1.2%), there was no statistically significant difference between the two arms (Mann-Whitney, p=0.72). Since luteal phase progesterone affects proliferation, we excluded 35 women that by serum progesterone levels could not be confirmed to be in the same phase of the menstrual cycle at baseline and off-study. Analyzing the remaining 117 for Ki-67 (42 placebo, 75 SDG), there was no significant change for the placebo arm (Wilcoxon, p=0.14) but the significant change in the SDG arm persisted (p=0.002). As an exploratory analysis, assessment of gene expression was performed by RT-qPCR on 77 pairs of non-bloody RPFNA specimens. 22 had significant ERα gene expression changes (defined &amp;lt;0.5 or &amp;gt;2.0 fold changes). There was no significant change over time for the placebo group (7/10 increases, Wilcoxon, p=0.16), but there was significant change for the SDG group (10/12 decreases, p=0.027). There was also a significant difference between the groups (Mann-Whitney, p=0.018). While the primary trial result is null, there is supportive evidence SDG may favorably affect cell proliferation and estrogen signaling in premenopausal women at high risk for development of breast cancer. Supported by Susan G. Komen Promise Grant KG101039. Study agent (Brevail®, placebo) provided by Lignan Research Inc. (later Barlean's Oils) which was otherwise not involved in the design, conduct, or analysis of the study. Citation Format: Carol J. Fabian, Seema A. Khan, Judy E. Garber, William C. Dooley, Lisa D. Yee, Carola M. Zalles, Trina Metheny, Teresa A. Phillips, Jinxiang Hu, Brian K. Petroff, Stephen D. Hursting, Bruce F. Kimler. Randomized clinical trial of a flaxseed lignan in pre-menopausal women at high risk for development of breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1120.

A combination of metabolite profiling and network pharmacology to explore the potential pharmacological changes of secoisolariciresinol-diglycoside.

The prototypes and metabolites formed from the use of traditional Chinese medicines (TCM) are typically the cause of both side side-effects and therapeutic results. Therefore, the characterization of in vivo substances and the determination of functional changes are of great importance for clinical applications. Secoisolariciresinol-diglycoside (SDG), one major compound in flaxseeds, was used as a potential drug to treat tumors in the clinic; however, the metabolism information and functional changes of SDG in vivo were limited, which limited its application. In this study, an integrated strategy based on metabolite profiling and network pharmacology was applied to explore the metabolism feature and functional changes of SDG. As a result, a total of 28 metabolites were found in rats, including 14 in plasma, 22 in urine, 20 in feces, 7 in the heart, 14 in the liver, 8 in the spleen, 10 in the lungs, 14 in the kidneys, and 4 in the brain. Among them, M8, M13 and M26 were the main metabolites of SDG in rats and 24 were characterized for the first time. The metabolic reactions contained phase I reactions of demethylation, dehydroxylation, deglycosylation, arabinosylation and glycosylation, and phase II reactions of glucuronidation and sulfation were also observed. Notably, the arabinosylation and glycosylation were found in SDG for the first time. Meanwhile, 121 targets of SDG and its metabolites were found, PRKCB was the main target of SDG, and the metabolites of SDG mainly targeted HSP90A1, IL6, AKT1, MAPK3, MTOR, PIK3CA, SRC, ESR1, AR, PIK3CB, and PIK3CB. The difference of targets between SDG and its metabolites could result in its additional functional pathways of neurotrophin signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway or indications of anti-prostate cancer. This work provided a new insight for exploring the mechanism and therapy indications of drugs.

Protective Effect of Secoisolariciresinol Diglycoside in Carbon Tetrachloride Induced Hepatotoxicity in Rats

Protective Effect of Secoisolariciresinol Diglycoside in Carbon Tetrachloride Induced Hepatotoxicity in Rats

Abstract 231: The polyphenolic plant lignan secoisolariciresinol diglycoside reduces mammary tumor growth, possibly via inhibition of local inflammatory signaling

Abstract Background: Secoisolariciresinol diglycoside (SDG) is a polyphenolic plant lignan found in flax and sesame seeds as well as legumes, whole grains, fruits and vegetables. It is metabolized by the gut bacteria into two major enterolignans: enterolactone (ENL) and enterodiol (END). These enterolignans have been associated with reduced breast cancer risk and progression in population studies as well as decreased tumor growth in preclinical models of breast cancer. Methods: The impact of SDG supplementation on tumor growth in a mouse model of basal-like breast cancer was examined. C57BL/6 mice were fed a control diet (10% kcal from fat) or control diet with SDG supplementation (100 mg/kg food) for eight weeks, then both groups were orthotopically injected with E0771 mammary tumor cells. An inflammatory signaling qPCR array (Qiagen) was performed on mammary tissue distal to tumor. Tumors were stained by immunohistochemistry (IHC) for Ki67 to measure proliferation levels and phospho-p65 to determine inflammatory signaling pathway activation. Tumors and mammary tissue were also stained for F4/80 to quantify macrophage infiltration. Serum level of hormones, adipokines, and cytokines were measured via luminex assay (Bio-Rad). Results: SDG supplementation significantly decreased tumor weight (p&amp;lt;0.05). SDG did not affect body weight or body fat percentage but did significantly decrease expression of F4/80, CRP, and other pro-inflammatory markers in the mammary tissue. IHC staining revealed no difference in tumor proliferation; however, SDG supplementation did reduce inflammatory signaling in the tumors, indicated by a significant decrease in phospho-p65 staining. However, serum cytokine levels were not significantly different between the groups. Tumors are currently being stained by IHC for cleaved caspase 3 to measure levels of apoptosis. In addition, cell culture experiments will be conducted to define the impact of ENL treatment on protumorigenic cross-talk between tumor cells, adipocytes, and macrophages. Specifically, the effects of conditioned media from adipocyte/macrophage co-cultures (with +/- ENL treatment) on mouse E0771 and human MDA-MB-231 tumor cell proliferation, migration and invasion will be examined. Conclusions: SDG supplementation reduced mammary tumor growth in association with SDG’s effects on local, but not systemic, inflammatory signaling. Citation Format: Claire G. Lineberger, Laura W. Bowers, Nikki A. Ford, Emily L. Rossi, Bruce K. Kimler, Carol J. Fabian, Stephen D. Hursting. The polyphenolic plant lignan secoisolariciresinol diglycoside reduces mammary tumor growth, possibly via inhibition of local inflammatory signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 231. doi:10.1158/1538-7445.AM2017-231

Therapeutic effect of Linum usitatissimum L. in STZ-nicotinamide induced diabetic nephropathy via inhibition of AGE's and oxidative stress.

The present study was aimed to evaluate the potential of petroleum ether and hydro-alcoholic extract of Linum usitatissimum (FPE and FHE) in STZ-nicotinamide induced diabetic nephropathy. GC-MS analysis of FPE revealed the presence of different fatty acids, heterocyclic compounds etc. Moreover, chromatography of FHE isolated Secoisolariciresinol diglycoside. After 30days of STZ-administration, 100, 200 and 400mg/kg of FPE and FHE were administered for 45days. FPE and FHE produced significant attenuation in the glycemic status, renal parameter, lipid profile and level of antioxidant enzymes proving efficacy in diabetic nephropathy. Moreover, FPE and FHE produced significant reduction in the formation of AGEs in kidney. The results indicated that via amelioration oxidative stress and formation of AGEs, FPE and FHE produced significant nephroprotective effect in STZ- induced diabetic nephropathy in rats.

The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor 1.

Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.

Abstract P2-05-28: The impact of the plant lignin secoisolariciresinol diglycoside on preclinical models of estrogen receptor positive breast cancer

Abstract Background: Several preclinical studies indicate that secoisolariciresinol diglycoside (SDG), a polyphenolic plant lignin found most abundantly in flaxseeds, inhibits the progression of both estrogen receptor (ER) positive and negative mammary tumors. SDG is metabolized by gut bacteria into the biologically active metabolites enterolactone (ENL) and enterodiol (END), which are known to have anti-estrogenic activity. However, the mechanisms mediating SDG's anti-tumor effects remain poorly understood. Methods: In a dose-determination pilot study linked to an ongoing clinical trial of SDG in women at high risk for breast cancer, 18 week old C57BL/6 mice were randomized to a control diet or SDG-supplemented diets (25 or 74 mg/kg of food) for 8 weeks prior to euthanization, and the levels of serum and tissue SDG metabolites (particularly ENL and END), metabolic hormones and inflammatory markers were measured. In an ongoing tumor study, 12-week old C57BL/6 and foxn1 nu/nu mice were randomized to the control or control plus SDG (100 mg/kg of food, a dose projected to match ENL and END metabolite levels achieved in the clinical trial) diet regimen. After 8 weeks on diet, they will receive orthotopic injections of E0771 mouse mammary tumor cells or BT-483 human breast cancer cells (both ER positive), continuing on the same diets until euthanization. Cell culture studies examining the impact of biologically relevant concentrations of ENL and END on E0771 and BT-483 cells are also in progress. Results: In comparison to those maintained on the control diet, the higher dose SDG diet reduced estrogen and pro-inflammatory signaling in the pilot study mice, as evidenced by higher interleukin 10 and lower C-reactive protein mammary fat pad expression as well as lower circulating levels of the adipokines leptin and resistin, which have been linked to chronic inflammation. High dose SDG also decreased serum insulin and glucose levels, indicating improved metabolic function. Because serum ENL and END levels in the pilot study did not reach those achieved in the SDG clinical trial, a 100 mg/kg SDG dose was chosen for the tumor study. Cell culture studies indicate that ENL (150 nM) inhibits E0771 and BT-483 cell proliferation and ER alpha:beta expression ratio. Conclusions: Preliminary data suggests that the anti-tumor effects of SDG's metabolites may be mediated through multiple mechanisms, including improvements in metabolic function and inflammatory signaling as well as modulation of breast cancer cell gene expression. The results of the ongoing tumor study will inform the design of additional cell culture studies aimed at further defining these mechanisms. Citation Format: Bowers LW, Ford NA, Rossi EL, Shamsunder MG, Kimler BF, Fabian CJ, Hursting SD. The impact of the plant lignin secoisolariciresinol diglycoside on preclinical models of estrogen receptor positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-28.

Secoisolariciresinol diglycoside, a flaxseed lignan, exerts analgesic effects in a mouse model of type 1 diabetes: Engagement of antioxidant mechanism

Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has been shown in our previous studies to exert antidepressant-like effect. As antidepressant drugs are clinically used to treat chronic neuropathic pain, this work aimed to investigate the potential analgesic efficacy of SDG against diabetic neuropathic pain in a mouse model of type 1 diabetes. We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (STZ, 200mg/kg), and Hargreaves test or von Frey test was used to assess thermal hyperalgesia or mechanical allodynia, respectively. Chronic instead of acute SDG treatment (3, 10 or 30mg/kg, p.o., twice per day for three weeks) ameliorated thermal hyperalgesia and mechanical allodynia in diabetic mice, and these analgesic actions persisted about three days when SDG treatment was terminated. Although chronic treatment of SDG to diabetic mice did not impact on the symptom of hyperglycemia, it greatly attenuated excessive oxidative stress in sciatic nerve and spinal cord tissues, and partially counteracted the condition of weight decrease. Furthermore, the analgesic actions of SDG were abolished by co-treatment with the reactive oxygen species donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the reactive oxygen species scavenger phenyl-N-tert-butylnitrone (PBN). These findings indicate that chronic SDG treatment can correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the analgesic actions of SDG in diabetic mice may be associated with its antioxidant activity.

Negative-Pressure Cavitation Extraction of Secoisolariciresinol Diglycoside from Flaxseed Cakes.

The negative-pressure cavitation extraction (NPCE) technique was applied firstly to extract secoisolariciresinol diglucoside (SDG) from flaxseed cakes. The significant extraction parameters were screened by fractional factorial design (FFD). The optimal parameters were determined using the central composite design (CCD) with the two variables, NaOH amount and the liquid/solid ratio. The conditions of the extraction were optimized by using response surface methodology (RSM). Under the optimal conditions, the extraction yield and the extraction purity of SDG was 16.25 mg/g and 3.86%, respectively. The efficiency of NPCE was compared with that of conventional extraction methods. Our results demonstrated that NPCE was comparable to the well-known ultrasound-assisted extraction in term of extraction yield and purity. This extraction technique has advantages of less time-consuming, low solvent usage and high throughput capability.

Metabolism of secoisolariciresinol-diglycoside the dietary precursor to the intestinally derived lignan enterolactone in humans

Secoisolariciresinol-diglycoside (SDG), a natural dietary lignan of flaxseeds now available in dietary supplements, is converted by intestinal bacteria to the mammalian lignans enterodiol and enterolactone. High levels of these lignans in blood and urine are associated with reduced risk of many chronic diseases. Our objective was to determine the bioavailability and pharmacokinetics of SDG in purified flaxseed extracts under dose-ranging and steady-state conditions, and to examine whether differences in secoisolariciresinol-diglycoside purity influence bioavailability. Pharmacokinetic studies were performed on healthy postmenopausal women after oral intake of 25, 50, 75, 86 and 172 mg of secoisolariciresinol-diglycoside. Extracts differing in secoisolariciresinol-diglycoside purity were compared, and steady-state lignan concentrations measured after daily intake for one week. Blood and urine samples were collected at timed intervals and secoisolariciresinol, enterodiol and enterolactone concentrations measured by mass spectrometry. Secoisolariciresinol-diglycoside was efficiently hydrolyzed and converted to secoisolariciresinol. Serum concentrations increased rapidly after oral intake, peaking after 5-7 h and disappearing with a plasma elimination half-life of 4.8 h. Maximum serum concentrations of the biologically active metabolites, enterodiol and enterolactone were attained after 12-24 h and 24-36 h, respectively, and the half-lives were 9.4 h and 13.2 h. Linear dose-responses were observed and secoisolariciresinol bioavailability correlated (r(2) = 0.835) with cumulative lignan excretion. There were no significant differences in the pharmacokinetics of extracts differing in purity, and steady-state serum lignan concentrations were obtained after one-week of daily dosing. In conclusion, this study defines the pharmacokinetics of secoisolariciresinol-diglycoside and shows it is first hydrolyzed and then metabolized in a time-dependent sequence to secoisolariciresinol, enterodiol and ultimately enterolactone, and these metabolites are efficiently absorbed.

Effect of Grain Tef (&lt;i&gt;Eragrostis tef &lt;/i&gt;(Zucc.) Trotter) Flour Substitutions with Flaxseed on Mineral Content, Antioxidant Activity, Phytic Acid Content and Microbial Quality of Injera

There is an increased global interest in the food industry to develop and market functional foods in which scientific investigations are limited in Ethiopia. Tef injera functional character can be further enhanced by substitution with flaxseed which is known to bear functional ingredients (α-linolenic acid an ω-3 fatty acid, secoisolariciresinol diglycoside lignans, dietary fibre and proteins). Two flaxseed forms (whole and flour) and three flaxseed substitution levels (3%, 6% and 9% flaxseed) arranged in a factorial experimental design in three replications were cofermented to find out whole or flour and at what substitution level injera with better nutrient and functional potential can be processed. Tef injera (100%) was used as a control. Tef injera substituted with flaxseed (whole and flour) at 3%, 6% and 9% showed a significant (P&lt;0.05) effect on minerals (except P), ferric ion reducing antioxidant power (FRAP), phytic acid and microbial quality of injera. With 9% flaxseed substitution FRAP, Zn and Ca contents percentage increase were: 102, 110 and 16; whereas phytic acid and Fe decreased by 76 and 19, respectively from the control. Between 2 to 6 injera storage days, yeast-mould (2.27 to 3.93 log cfug-1) and total aerobic plate counts (ND to 3.77 log cfug-1) were lowest for 9% flaxseedsubstitution and highest for the control injera (2.85 to 4.08 log cfug-1 and 3.70 to 4.30 log cfug-1, respectively). Coliforms were not detected. Whole flaxseed substituted injera had high minerals, antioxidant and microbial stability than flour flaxseed substituted injera. Injera with high minerals (except iron) and antioxidant of improved microbial stability, low phytic acid contents can be processed by 9% flaxseed substitution.

Flax and Breast Cancer

Flax is a food and dietary supplement commonly used for menopausal symptoms. Flax is known for its lignan, α-linolenic acid, and fiber content, components that may possess phytogestrogenic, anti-inflammatory, and hormone modulating effects, respectively. We conducted a systematic review of flax for efficacy in improving menopausal symptoms in women living with breast cancer and for potential impact on risk of breast cancer incidence or recurrence. We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to January 2013 for human interventional or observational data pertaining to flax and breast cancer. Of 1892 records, we included a total of 10 studies: 2 randomized controlled trials, 2 uncontrolled trials, 1 biomarker study, and 5 observational studies. Nonsignificant (NS) decreases in hot flash symptomatology were seen with flax ingestion (7.5 g/d). Flax (25 g/d) increased tumor apoptotic index (P< .05) and decreased HER2 expression (P< .05) and cell proliferation (Ki-67 index; NS) among newly diagnosed breast cancer patients when compared with placebo. Uncontrolled and biomarker studies suggest beneficial effects on hot flashes, cell proliferation, atypical cytomorphology, and mammographic density, as well as possible anti-angiogenic activity at doses of 25 g ground flax or 50 mg secoisolariciresinol diglycoside daily. Observational data suggests associations between flax and decreased risk of primary breast cancer (adjusted odds ratio [AOR] = 0.82; 95% confidence interval [CI] = 0.69-0.97), better mental health (AOR = 1.76; 95% CI = 1.05-2.94), and lower mortality (multivariate hazard ratio = 0.69; 95% CI = 0.50-0.95) among breast cancer patients. Current evidence suggests that flax may be associated with decreased risk of breast cancer. Flax demonstrates antiproliferative effects in breast tissue of women at risk of breast cancer and may protect against primary breast cancer. Mortality risk may also be reduced among those living with breast cancer.

Quality evaluation of flaxseed oil obtained by different extraction techniques

Quality of flaxseed oil obtained by supercritical fluid extraction (SFE) and accelerated solvent extraction (ASE) was evaluated and compared with that of the conventional solvent extraction (SE). The oil yield obtained by SFE, ASE and SE was 36.49, 41.90 and 42.40 g/100 g, respectively. There were no significant differences between ASE and SE oils in their physicochemical properties and fatty acid profiles; however SFE oil showed significantly lower melting point (MP), peroxide value (PV) and saturated fatty acids and higher iodine value (IV) and polyunsaturated fatty acids (PUFAs). Furthermore, SFE oil showed significantly higher phenolic acid content (47.58 μg/g) as compared to 20.88 μg/g and 15.69 μg/g in ASE and SE oils, respectively. The main flaxseed lignan; secoisolariciresinol diglycoside (SDG) was found only in the SFE oil (32.28 μg/g). Oils did not differ significantly in their tocopherol contents which ranged from 34.47 to 34.88 mg/g. These results advocate the use of SFE for flaxseed oil extraction.