Anti-inflammatory effect of lignans from flaxseed after fermentation by lactiplantibacillus plantarum SCB0151 in vitro.

Lignan, a beneficial constituent of Flaxseed (Linum usitatissimum L.) showed great interest in researchers because of its multiple functional properties. Nonetheless, a challenge arises due to the glycosidic structure of lignans, which the gut epithelium cannot readily absorb. Therefore, we screened 18 strains of Lactiplantibacillus plantarum, Lacticaseibacillus casei, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Pediococcus pentosaceus, Pediococcus acidilactici, and Enterococcus durans to remove glycosides from flaxseed lignan extract enzymatically. Among our findings, Lactiplantibacillus plantarum SCB0151 showed the highest activity of ß-glucosidase (8.91 ± 0.04 U/mL) and higher transformed efficiency of Secoisolariciresinol (SECO) (8.21 ± 0.13%). The conversion rate of Secoisolariciresinol diglucoside (SDG) and the generation rate of SECO was 58.30 ± 3.78% and 32.13 ± 2.78%, respectively, under the optimized conditions. According to the LC-HRMSMS analysis, SECO (68.55 ± 6.57 µM), Ferulic acid (FA) (32.12 ± 2.50 µM), and Coumaric acid (CA) (79.60 ± 6.21 µM) were identified in the biotransformation products (TP) of flaxseed lignan extract. Results revealed that the TP exhibited a more pronounced anti-inflammatory effect than the flaxseed lignan extract. SECO, FA, and CA demonstrated a more inhibitory effect on NO than that of SDG. The expression of iNOS and COX-2 was significantly suppressed by TP treatment in LPS-induced Raw264.7 cells. The secretion of IL-6, IL-2, and IL-1ß decreased by 87.09 ± 0.99%, 45.40 ± 0.87%, and 53.18 ± 0.83%, respectively, at 60 µg/mL of TP treatment. Given these data, the bioavailability of flaxseed lignan extract and its anti-inflammatory effect were significantly enhanced by Lactiplantibacillus plantarum SCB0151, which provided a novel approach to commercializing flaxseed lignan extract for functional food.

Selected 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors. A look into their use and potential in pre-diabetes and type 2 diabetes.

Objectives. This review assesses the comparative safety and efficacy of selected 3-hydroxy-3-methylglutaric acid coenzyme A inhibitors (statins, cinnamic acids. 3-hydroxy-3-methyl glutaric acid) on the pre-onset type 2 diabetes (PT2D) and post-onset type 2 diabetes (T2D)-related cluster of seven features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation and inflammation). Methods. Google scholar and PubMed were searched for statin*, flaxseed lignan complex (FLC), cinnamic acid (CA)*, and 3-hydroxy-3-methylglutaric acid (HMGA) in conjunction with each of PT2D, T2D and the cluster of seven. An introduction was followed by findings or absence thereof on the impacts of each of statins, FLC, CAs and HMGA on each member of the cluster of seven. Results. Pravastatin manages three features in PT2D, while a number of the statins improve five in T2D. FLC is negative in PT2D but controls four in T2D; it is not clear if the CAs and HMGA in FLC play a role in this success. CAs have potential in six and HMGA has potential in three of the cluster of seven though yet CAs and HMGA are untested in PT2D and T2D in humans. There are safety concerns with some statins and HMGA but FLC and CAs appear safe in the doses and durations tested. Conclusions. Selected statins, FLC, CAs and HMGA can manage or have a potential to manage at least three features of the cluster of seven. Most of the literature-stated concerns are with select statins but there are concerns (one actual and two potential) with HMGA.

Evaluation of protective efficacy of flaxseed lignan-Secoisolariciresinol diglucoside against mercuric chloride-induced nephrotoxicity in rats.

The toxicity of heavy metals such as mercury (Hg) in humans and animals is well documented. The kidney is the primary deposition site of inorganic-Hg and target organ of its toxicity. The present study investigated the protective efficacy of flaxseed lignan-Secoisolariciresinol diglucoside (SDG) on nephrotoxicity induced by mercuric chloride (HgCl2). Rats were intraperitoneally injected with HgCl2 (2 mg/kg/day) and renal toxicity was induced. Subcutaneous administration of rats with SDG (5 mg/kg/day) as a pre-treatment caused a significant reversal of HgCl2 induced increase in blood urea, creatinine, glutathione s-transferase and catalase (CAT). On the other hand, administration of SDG with HgCl2 restored normal levels of albumin and superoxide dismutase (SOD). Histological examination of kidneys confirmed that pre-treatment of SDG before HgCl2 administration significantly reduced its pathological effects. Thus, the results of the present investigation suggest that SDG can significantly reduce renal damage, serum and tissue biochemical profiles caused by HgCl2 induced nephrotoxicity. Hence, SDG may be recommended for clinical trials in the treatment of kidney disorders caused by exposure to Hg.

Flaxseed Lignan Alleviates the Paracetamol-Induced Hepatotoxicity Associated with Regulation of Gut Microbiota and Serum Metabolome.

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.

Secoisolariciresinol diglucoside protects against cadmium-induced oxidative stress-mediated renal toxicity in rats.

BACKGROUND: Cadmium is a well known environmental pollutant and strong toxic heavy metal, that causes oxidative damage to various organs of the body, including the kidney. Cadmium (II) chloride (CdCl2) is a water-soluble crystalline form, which exhibits a higher affinity with chlorides at the target site. The current study examined the protective effects of Secoisolariciresinol diglucoside (SDG), a principal lignan extracted from flaxseeds against CdCl2-induced renal toxicity in rats. METHODS: Twenty four healthy male Wistar rats with four groups of six animals each were used in the study. Group-1- Control was administered with saline. Group-2 -was treated with SDG; Group-3 with CdCl2 alone, and Group-4 were treated with CdCl2 plus SDG. The effect of Cd on kidney was assessed in terms of various parameters like lipid peroxidation, production of Nitric oxide (NO) and Myeloperoxidase (MPO), and kidney function markers like uric acid, urea, and creatinine. The levels of antioxidant molecules like glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were also measured, apart from histopathological studies. RESULTS: The animals that received CdCl2, exhibited changes in the concentration of Cd in the kidney. The levels of kidney function markers like uric acid, urea, and creatinine were found to be abnormal in serum, and also there was a drastic decrease in the levels of glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The treatment of SDG significantly decreased (p < 0.05) the levels of NO and MPO in the animals treated with CdCl2 plus SDG when compared to the animal group treated with CdCl2 alone. The treatment of SDG before CdCl2 injection exhibited significant changes in the activity of the antioxidant enzymes, which was evidenced by the restoration in their activities, when compared to CdCl2 alone treated group (p < 0.05), as observed in the results of histopathology. CONCLUSIONS: The findings of the present investigation suggested that SDG exhibited anti-oxidant, anti-apoptotic and renoprotective properties. Thus, SDG may act as a supramolecular binding component and naturally occurring metal chelating agent for metal cations like Cd2+. Therefore, flaxseed lignan-SDG can be used as a therapeutic agent against nephrotoxicity caused by cadmium. However, detailed future studies are needed to know the underlying mechanism of action of SDG against the Cd and other heavy metals induced nephrotoxicity.

Effect of flaxseed polyphenols on physical stability and oxidative stability of flaxseed oil-in-water nanoemulsions.

Recent studies have shown that the high susceptibility of flaxseed oil nanoemulsions to lipid oxidation limits their incorporation into functional foods and beverages. For this reason, the impact of various flaxseed phenolic extracts on the physical and oxidative stability of flaxseed oil nanoemulsions was investigated. Flaxseed lignan extract (FLE) and secoisolariciresinol (SECO) exhibited antioxidant activity whereas secoisolariciresinol diglucoside (SDG) and p-coumaric acid (CouA) exhibited prooxidant activity in the flaxseed oil nanoemulsions. The antioxidant potential of flaxseed phenolics in the nanoemulsions was as follows: SECO < CouA < SDG ≈ FLE. Moreover, the antioxidant/prooxidant activity of the phenolics was also related to their free radical scavenging activity and partitioning in the nanoemulsions. Our results suggested that both SECO and FLE were good plant-based antioxidants for improving the stability of flaxseed oil nanoemulsions.

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.