PMID: 

PLoS One. 2019 ;14(10):e0223070. Epub 2019 Oct 17. PMID: 31622373

Abstract Title: 

Alteration of adipose tissue immune cell milieu towards the suppression of inflammation in high fat diet fed mice by flaxseed oil supplementation.

Abstract: 

The present study evaluates the effect of flaxseed oil (FXO) supplementation on adipose tissue macrophages (ATM's), E and D series resolvin (Rv) levels and adipose tissue inflammation. Male C57BL/6J mice were divided into five groups (n = 5): lean group (given standard chow diet), HFD group given high fat diet (approx. 18 weeks) till they developed insulin resistance and 4, 8 or 16 mg/kg group (HFD group later orally supplemented with 4, 8 or 16 mg/kg body weight flaxseed oil) for 4 weeks.The present study showed that FXO supplementation led to enhanced DHA, EPA, RvE1-E2, RvD2, RvD5- D6, IL-4, IL-10 and arginase 1 levels in ATMs together with altered immune cell infiltration and reduced NF-κB expression. The FXO supplementation suppresses immune cell infiltration into adipose tissue and alters adipose tissue macrophage phenotype towards the anti-inflammatory state via enhancement of E and D series resolvins, arginase 1 expression and anti-inflammatory cytokines level (IL-4 and IL-10.) leading to amelioration of insulin resistance in flaxseed oil supplemented HFD mice.

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PMID: 

Nutrients. 2019 Nov 4 ;11(11). Epub 2019 Nov 4. PMID: 31689992

Abstract Title: 

Effects of Flaxseed and Its Components on Mammary Gland MiRNome: Identification of Potential Biomarkers to Prevent Breast Cancer Development.

Abstract: 

Breast cancer is the most common cancer among women worldwide. We previously showed that early-life exposure to flaxseed (FS) or its components, FS oil (FSO) and secoisolariciresinol diglucoside (SDG), affects the mammary gland (MG) and is associated with the reduction of breast cancer risk during adulthood. However, the underlying mechanisms are not understood. This study aimed to investigate the effect of FS, FSO, and SDG on the MG miRNA signature at a late stage of development. Female C57BL/6 mice, 4-5 weeks of age, were randomized into four groups to receive: (i) basal AIN-93G, (ii) 10% FS, (iii) 3.67% FSO, or (iv) 0.15% SDG. After 21 days, the mice were sacrificed and MG miRNAs were profiled. Diet-specific MG miRNA signatures were identified. Deregulated miRNAs were associated with breast cancer and targeted genes involved in MG development, growth, and cancer. The study allowed for the identification of potential biomarkers or novel therapeutic targets to prevent and/or reduce the risk of breast cancer.

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PMID: 

Clin Nutr Res. 2019 Oct ;8(4):284-295. Epub 2019 Oct 2. PMID: 31720254

Abstract Title: 

The Effect of Flaxseed Enriched Yogurt on the Glycemic Status and Cardiovascular Risk Factors in Patients with Type 2 Diabetes Mellitus: Randomized, Open-labeled, Controlled Study.

Abstract: 

: Flaxseed is one of the rich sources ofα-linolenic acid and lignan. Flaxseed and its components have antioxidant, hypolipidemic and hypoglycemic effects. The study aimed to investigate the effect of flaxseed enriched yogurt on glycemic control, lipid profiles and blood pressure in patients with type 2 diabetes. A randomized, open-labeled, controlled clinical trial was conducted on 57 patients with type 2 diabetes. Participants were assigned to receive 200 g 2.5% fat yogurt containing 30-g flaxseed or plain yogurt daily for 8 weeks. Anthropometrics and biochemical parameters were evaluated at the beginning and end of the study. After 8 weeks of supplementation, Hemoglobin A1c was significantly decreased in the intervention group compared to control (p = 0.007). Also, at the end of the study, significant differences were seen between the flaxseed enriched yogurt and control groups in triglycerides and total cholesterol concentrations (p = 0.04 and p = 0.01), systolic blood pressure and diastolic blood pressure (p = 0.02 and p = 0.002, respectively). However, we did not find any difference between 2 groups in low-density lipoprotein, high-density lipoprotein, body weight and waist circumference (p>0.05). Our results showed that the addition of flaxseed to yogurt can be effective in the management of type 2 diabetes.Trial Registration: ClinicalTrials.gov Identifier: NCT02436369.

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PMID: 

Ocul Surf. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31734510

Abstract Title: 

An artificial tear containing flaxseed oil for treating dry eye disease: A randomized controlled trial.

Abstract: 

PURPOSE: To evaluate the efficacy and safety of a nano-emulsion artificial tear (OM3) containing carboxymethylcellulose (CMC) and glycerin, flaxseed oil and castor oil, and three osmoprotectants (levocarnitine, erythritol, and trehalose) compared with an artificial tear (Refresh Optive Advanced [ROA]) containing the same ingredients with the exception of trehalose and flaxseed oil.METHODS: In this multicenter, double-masked, randomized, two-arm, parallel-group, 6-visit study (screening, baseline, and days 7, 30, 60, and 90), subjects with dry eye disease underwent an open-label, 7-day run-in with CMC 0.5% (Refresh Plus), before 1:1 randomization to OM3 or ROA for 90 days (both instilled≥2 daily). Ocular Surface Disease Index (OSDI; primary endpoint change from baseline at day 90), tear film breakup time (TBUT), and ocular staining (combined/corneal/conjunctival) were assessed; change from baseline in these parameters was calculated at each timepoint. Treatment-related adverse events (AEs) were assessed at each visit.RESULTS: Overall, 242 subjects were randomized (OM3, n = 120; ROA, n = 122). At day 90, significant improvements in OSDI, ocular staining and TBUT were evident in both treatment groups. Significant (P 

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PMID: 

Cytokine. 2019 Nov 15 ;126:154922. Epub 2019 Nov 15. PMID: 31739218

Abstract Title: 

Effect of flaxseed supplementation on markers of inflammation and endothelial function: A systematic review and meta-analysis.

Abstract: 

OBJECTIVES: The rationale for the current study was to evaluate the efficacy of flaxseed supplementation on important adhesion molecules and inflammatory cytokines in adults.METHODS: We conducted searches of published literature in PubMed, Scopus, Web of Science, and Google Scholar databases from inception until May 2019. All randomized controlled trials (RCTs) which investigated the effects of flaxseed supplementation on the circulating concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular cell adhesion protein 1 (VCAM-1), E-selectin, and intercellular adhesion molecule 1 (ICAM-1) were included in our analysis. Results were summarized using weighted mean differences (WMDs) by random-effects model.RESULTS: Forty eligible RCTs, including 2520 participants were identified. The results of the meta-analysis revealed flaxseed supplementation reduced the concentrations of CRP (WMD = -0.387 mg/L; 95% CI: -0.653, -0.121, p = 0.004), IL-6 (WMD = -0.154 pg/Ml; 95% CI: -0.299, -0.010, p = 0.036), and VCAM-1 (WMD = -22.809 ng/ml; 95% CI: -41.498, -4.120, p = 0.017) but had no significant effect on TNF-α (WMD = -0.077 pg/mL; 95% CI: -0.317, 0.163, p = 0.530), ICAM-1 (WMD = -8.610 ng/ml; 95% CI: -21.936, 4.716, p = 0.205), and E-selectin (WMD = -1.427 ng/ml; 95% CI: -4.074, 1.22, p = 0.291).CONCLUSIONS: These findings showed that flaxseed supplementation may improve some circulating concentrations of specific adhesion molecules and inflammatory cytokines. However, well-designed trials are needed to confirm the range of non-significant and/or equivocal findings.

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PMID: 

Oncol Rep. 2019 Nov ;42(5):1904-1914. Epub 2019 Aug 28. PMID: 31485597

Abstract Title: 

Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells.

Abstract: 

Apoptosis is regarded as a therapeutic target because it is typically disturbed in human cancer. Silymarin from milk thistle (Silybum marianum) has been reported to exhibit anticancer properties via regulation of apoptosis as well as anti‑inflammatory, antioxidant and hepatoprotective effects. In the present study, the effects of silymarin on the inhibition of proliferation and apoptosis were examined in human gastric cancer cells. The viability of AGS human gastric cancer cells was assessed by MTT assay. The migration of AGS cells was investigated by wound healing assay. Silymarin was revealed to significantly decrease viability and migration of AGS cells in a concentration‑dependent manner. In addition, the number of apoptotic bodies and the rate of apoptosis were increased in a dose‑dependent manner as determined by DAPI staining and Annexin V/propidium iodide double staining. The changes in the expression of silymarin‑induced apoptosis proteins were investigated in human gastric cancer cells by western blotting analysis. Silymarin increased the expression of Bax, phosphorylated (p)‑JNK and p‑p38, and cleaved poly‑ADP ribose polymerase, and decreased the levels of Bcl‑2 and p‑ERK1/2 in a concentration‑dependent manner. The in vivo tumor growth inhibitory effect of silymarin was investigated. Silymarin (100 mg/kg) significantly decreased the AGS tumor volume and increased apoptosis, as assessed by the TUNEL assay, confirming its tumor‑inhibitory effect. Immunohistochemical staining revealed elevated expression of p‑JNK and p‑p38 as well as reduced expression of p‑ERK1/2 associated with silymarin‑treatment. Silymarin was revealed to reduce tumor growth through inhibition of p‑ERK and activation of p‑p38 and p‑JNK in human gastric cancer cells. These results indicated that silymarin has potential for development as a cancer therapeutic due to its growth inhibitory effects and induction of apoptosis in human gastric cancer cells.

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PMID: 

Dermatol Ther. 2019 Oct 3:e13095. Epub 2019 Oct 3. PMID: 31579978

Abstract Title: 

Efficacy and safety of oral silymarin in comparison with oral doxycycline and their combination therapy in the treatment of acne vulgaris.

Abstract: 

Two factors of oxidative stress and inflammatory processes are implicated in pathogenesis of acne vulgaris. Silymarin has antioxidant and anti-inflammatory activities. This study was done to evaluate the effect of oral silymarin in the treatment of acne vulgaris compared to doxycycline and also their combination therapy. This randomized controlled trial was performed on 60 patients with acne vulgaris were divided into three groups of 20 patients, including: Silymarin (Group 1), Doxycycline (Group 2), and both compounds (Group 3). The patients' response was monitored every month and the lesions were evaluated using photography and two methods of Global Acne Grading system (GAGS) and Acne Severity Index (ASI). According to the results, the response to silymarin was not significantly different with doxycycline in the GAGS index (p = .260), but was lower in the ASI (p = .021). In this study, the synergistic effects of silymarin and doxycycline combination have been investigated in comparison with doxycycline. Although the improvement was more favorable in combination group, there was no statistically significant difference (p = .9 in ASI and p = .5 in GAGS). The results of our study suggest that although the silymarin monotherapy is not as effective as doxycycline for the treatment of acne vulgaris, it can be a therapeutic option.

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PMID: 

J Mol Neurosci. 2019 Nov 15. Epub 2019 Nov 15. PMID: 31732923

Abstract Title: 

Silymarin Protects Against Impaired Autophagy Associated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinsonism.

Abstract: 

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exacerbates mitochondrial impairment andα-synuclein expression leading to Parkinsonism. Impaired mitochondria and over-expressed α-synuclein are degraded and eliminated via macroautophagy and chaperone-mediated autophagy. Owing to multiple properties, silymarin protects from oxidative stress-mediated cellular injury. However, its effecton MPTP-induced changes in autophagy is not yet known. The study aimed to decipher the effect of silymarin on MPTP-induced changes in autophagy. Male mice (20-25 g) were treated with silymarin (intraperitoneally, daily, 40 mg/kg) for 2 weeks. On day 7, a few animals were also administered with MPTP(intraperitoneally, 20 mg/kg, 4 injections at 2-h interval) along with vehicles. Striatal dopamine content was determined. Western blot analysis was done to assess α-synuclein, beclin-1, sequestosome, phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), lysosome-associatedmembrane protein-2 (LAMP-2), heat shock cognate-70 (Hsc-70), LAMP-2A, phosphorylated unc-51-like autophagy activating kinase (p-Ulk1), and phosphorylated mechanistic target of rapamycin (p-mTOR) levels in the nigrostriatal tissue. Silymarin rescued from MPTP-induced increase in beclin-1, sequestosome, p-AMPK, and p-Ulk1 and decrease in LAMP-2, p-mTOR, and LAMP-2A levels. Silymarin defended against MPTP-induced increase in α-synuclein and reduction in dopamine content. The results demonstrate that silymarin protects against MPTP-induced changes in autophagy leading to Parkinsonism.

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PMID: 

J Immunoassay Immunochem. 2019 Nov 18:1-13. Epub 2019 Nov 18. PMID: 31739724

Abstract Title: 

Hepatoprotective effect of artichoke leaf extracts in comparison with silymarin on acetaminophen-induced hepatotoxicity in mice.

Abstract: 

Acetaminophen is a common analgesic-antipyretic agent, which is safe in therapeutic doses but in higher doses can produce hepatic necrosis. The aim of this study is to investigate the hepatoprotective effects of artichoke, silymarin, and both agents in acetaminophen-induced liver damage in mice. Forty male mice were divided into five main groups, (1) control (2) Acetaminophen (APAP) (3) Artichoke leaf extracts (ALE) and APAP (4) silymarin and APAP group (5) ALE, silymarin and APAP groups. Blood samples were collected for the measurement of liver enzymes (ALT, AST, and ALP). The liver was excised, weighed and dissected into two parts, one used for measurement of malondialdehyde (MDA) and glutathione reductase, and the other part used for histopathological examination and assessment of proliferative cell nuclear antigen (PCNA) immunohistochemical expression. APAP group showed a significant increase in liver weight, ALT, AST, ALP, MDA, and PCNA expression with a significant decrease in glutathione reductase in comparison to control group. All these parameters were significantly improved in the three treated groups when compared to APAP group. APAP group showed marked portal inflammation and parenchyma necrosis. Co-administration of ALE and/or silymarin to acetaminophen treated mice showed a significant reduction in PCNA expression compared to APAP group. Both ALE and silymarin co-treatment showed a significant decrease in PCNA percentage to a level near to control group. Artichoke and/or silymarin are suggested to protect against acetaminophen-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect, decreasing liver damage and proliferation.ALT, alanine transaminase. AST, aspartate transaminase. ALP, alkaline phosphatase.MDA, malondialdehyde. PCNA, proliferative cell nuclear antigen.

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PMID: 

Phytother Res. 2018 Jul ;32(7):1382-1387. Epub 2018 Mar 9. PMID: 29520889

Abstract Title: 

Efficacy of artichoke leaf extract in non-alcoholic fatty liver disease: A pilot double-blind randomized controlled trial.

Abstract: 

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and is potentially treatable, though there are few therapeutic agents available. Artichoke leaf extract (ALE) has shown potential as a hepatoprotective agent. This study sought to determine if ALE had therapeutic utility in patients with established NAFLD. In this randomized double-blind placebo-controlled parallel-group trial, 100 subjects with ultrasound-diagnosed NAFLD were randomized to either ALE 600 mg daily or placebo for a 2-month period. NAFLD response was assessed by liver ultrasound and serological markers including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and AST to platelet ratio index (APRI) score. Ninety patients completed the study (49 ALE and 41 placebo) with no side effects reported. ALE treatment compared with placebo: Doppler sonography showed increased hepatic vein flow (p 

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