Enhanced ileum function in weaned piglets via Laminaria digitata and alginate lyase dietary inclusion: A combined proteomics and metabolomics analysis.

Laminaria digitata, a brown seaweed with prebiotic properties, can potentially enhance the resilience of weaned piglets to nutritional distress. However, their cell wall polysaccharides elude digestion by monogastric animals' endogenous enzymes. In vitro studies suggest alginate lyase's ability to degrade such polysaccharides. This study aimed to assess the impact of a 10% dietary inclusion of L. digitata and alginate lyase supplementation on the ileum proteome and metabolome, adopting a hypothesis-generating approach. Findings indicated that control piglets escalated glucose usage as an enteric energy source, as evidenced by the increased abundance of PKLR and PCK2 proteins and decreased tissue glucose concentration. Additionally, the inclusion of seaweed fostered a rise in proteins linked to enhanced enterocyte structural integrity (ACTBL2, CRMP1, FLII, EML2 and MYLK), elevated peptidase activity (NAALADL1 and CAPNS1), and heightened anti-inflammatory activity (C3), underscoring improved intestinal function. In addition, seaweed-fed piglets showed a reduced abundance of proteins related to apoptosis (ERN2) and proteolysis (DPP4). Alginate lyase supplementation appeared to amplify the initial effects of seaweed-only feeding, by boosting the number of differential proteins within the same pathways. This amplification is potentially due to increased intracellular nutrient availability, making a compelling case for further exploration of this dietary approach. SIGNIFICANCE: Pig production used to rely heavily on antibiotics and zinc oxide to deal with post-weaning stress in a cost-effective way. Their negative repercussions on public health and the environment have motivated heavy restrictions, and a consequent search for alternative feed ingredients/supplements. One of such alternatives is Laminaria digitata, a brown seaweed whose prebiotic components that can help weaned piglets deal with nutritional stress, by improving their gut health and immune status. However, their recalcitrant cell walls have antinutritional properties, for which alginate lyase supplementation is a possible solution. By evaluating ileal metabolism as influenced by dietary seaweed and enzyme supplementation, we aim at discovering how the weaned piglet adapts to them and what are their effects on this important segment of the digestive system.

Effects of sulfated polysaccharides from Laminaria japonica on regularating the gut microbiotan and alleviating intestinal inflammation in obese mice.

Due to their known health-enhancing properties, Laminaria japonica polysaccharides (LJP) may alleviate obesity via unknown mechanisms. This study aimed to investigate beneficial LJP effects and mechanism(s) of action using an animal obesity model (ICR mice fed a high-fat diet). First, LJP were confirmed to consist of sulfated polysaccharides via infrared spectroscopy. Next, LJP administration to mice was found to induce weight loss, reduce liver fat accumulation, and support healthy obesity-related blood serum indicator levels. Notably, LJP treatment significantly reduced TC and LDL levels and significantly increased HDL, LPL, UCP-2, and PPAR-α levels. Furthermore, examinations of tissues of LJP-treated mice revealed significantly reduced intestinal tissue inflammation as compared to corresponding results obtained for untreated obese controls. Additionally, LJP treatment relieved colonic shortening and reduced colonic levels of inflammatory factors TNF-α and IL-6. Further exploration of LJP treatment effects on mouse gut microbiota conducted via fecal 16S rRNA gene sequence-based gut microbiome profiling analysis revealed that LJP treatment increased the Bacteroidetes/Firmicutes ratio and increased gut abundances of probiotics Bacteroides acidifaciens, s_Lactobacillus intestinalis, and s_Lactobacillus murinus. In conclusion, these results collectively suggest that LJP use as a food supplement may alleviate obesity and related gut microbiota dysbiosis and intestinal inflammatory disorders.

Two Laminaria japonica polysaccharides with distinct structure characterization affect gut microbiota and metabolites in hyperlipidemic mice differently.

Our previous study found dietary mannogluconic acid (MA) and fucogalactan sulfate (FS) from Laminaria japonica have distinct structure characterization and potential hypolipidemic effects in vitro. Herein, we compared the benefits of MA and FS on hyperlipidemia. The result showed only FS treatment decreased body weight and serum cholesterol levels. Compared with MA, FS was more effective in mitigating hepatic fat accumulation, promoting GSH-Px activity, reducing the MDA formation, and lowering the level of TNF-α in liver. Gut microbiota and metabolism analysis revealed that FS increased the relative abundance of beneficial bacteria and boosted the level of short chain fatty acids. Particularly, taurine and 3α,7α,12α-trihydroxy-24-oxo-5-ß-cholestanoyl CoA were upregulated by FS, which might attribute to the increased Oscillibacter and thus affect the enterohepatic circulation of bile acids and serum TC level. Therefore, FS with more branches and sulfate ester groups could be a good lipid-lowering dietary supplement.

Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of Ecklonia cava Fucoidan against Metastatic Lung Cancer.

Although fucoidan, a well-studied seaweed-extracted polysaccharide, has shown immune stimulatory effects that elicit anticancer immunity, mucosal adjuvant effects via intranasal administration have not been studied. In this study, the effect of Ecklonia cava-extracted fucoidan (ECF) on the induction of anti-cancer immunity in the lung was examined by intranasal administration. In C57BL/6 and BALB/c mice, intranasal administration of ECF promoted the activation of dendritic cells (DCs), natural killer (NK) cells, and T cells in the mediastinal lymph node (mLN). The ECF-induced NK and T cell activation was mediated by DCs. In addition, intranasal injection with ECF enhanced the anti-PD-L1 antibody-mediated anti-cancer activities against B16 melanoma and CT-26 carcinoma tumor growth in the lungs, which were required cytotoxic T lymphocytes and NK cells. Thus, these data demonstrated that ECF functioned as a mucosal adjuvant that enhanced the immunotherapeutic effect of immune checkpoint inhibitors against metastatic lung cancer.

Seaweeds rehydration and boiling: Impact on iodine, sodium, potassium, selenium, and total arsenic contents and health benefits for consumption.

Considering the importance of seaweeds for the development of sustainable and innovative food products, this study aimed to characterize the impact of hydrothermal processing on iodine, sodium, potassium, selenium, and arsenic concentrations of four seaweed species (S. latissima, L. digitata, U. pinnatifida, and C. crispus) and on the associated health risks-benefits for consumers. These elements revealed a common pattern for leachable fractions of iodine, total arsenic, and selenium: L. digitata ≥ S. latissima > C. crispus > U. pinnatifida after rehydration and boiling during different periods. The behavior for sodium was: S. latissima > L. digitata > C. crispus > U. pinnatifida, and for potassium: U. pinnatifida > L. digitata > S. latissima > C. crispus. Generally, the species that attained more significant losses were S. latissima and L. digitata. A health-relevant sodium/potassium ratio below 0.7 was found for all species except for U. pinnatifida. In some species, the risk-benefit analysis revealed that high iodine and arsenic levels might promote risks for consumption, even after 20 min boiling, but 5 g of processed U. pinnatifida could contribute to adequate iodine, sodium, potassium, and selenium intakes for all population groups. Standardized processing treatments of seaweeds can open new opportunities for the sector.

Aquaculture Production of the Brown Seaweeds Laminaria digitata and Macrocystis pyrifera: Applications in Food and Pharmaceuticals.

Seaweeds have a long history of use as food, as flavouring agents, and find use in traditional folk medicine. Seaweed products range from food, feed, and dietary supplements to pharmaceuticals, and from bioenergy intermediates to materials. At present, 98% of the seaweed required by the seaweed industry is provided by five genera and only ten species. The two brown kelp seaweeds Laminaria digitata, a native Irish species, and Macrocystis pyrifera, a native New Zealand species, are not included in these eleven species, although they have been used as dietary supplements and as animal and fish feed. The properties associated with the polysaccharides and proteins from these two species have resulted in increased interest in them, enabling their use as functional foods. Improvements and optimisations in aquaculture methods and bioproduct extractions are essential to realise the commercial potential of these seaweeds. Recent advances in optimising these processes are outlined in this review, as well as potential future applications of L. digitata and, to a greater extent, M. pyrifera which, to date, has been predominately only wild-harvested. These include bio-refinery processing to produce ingredients for nutricosmetics, functional foods, cosmeceuticals, and bioplastics. Areas that currently limit the commercial potential of these two species are highlighted.

Fucoxanthin extracted from Laminaria Japonica inhibits metastasis and enhances the sensitivity of lung cancer to Gefitinib.

ETHNOPHARMACOLOGICAL RELEVANCE: Laminaria japonica, a brown seaweed, has been used in Traditional Chinese Medicine (TCM) to treat a variety of diseases including lung cancer. AIM OF THE STUDY: To demonstrate the effects of Fucoxanthin (FX), a major active component extracted from Laminaria japonica on metastasis and Gefitinib (Gef) sensitivity in human lung cancer cells both in vitro and in vivo. MATERIALS AND METHODS: Invasion and migration of lung cancer cells were detected using the wound healing assay and transwell assay. Epithelial-to-mesenchymal transition (EMT) factors and PI3K/AKT/NF-κB pathways were analyzed by western blotting. RNA interference (RNAi) technology was used to silence TIMP-2 gene expression in A549 cells. The anti-metastatic effect of FX was evaluated in vivo in an experimental lung metastatic tumor model. On the other hand, cell counting kit-8 assay was used to study the cell viability of human lung cancer PC9 cells and Gef resistant PC9 cells (PC9/G) after Gef, FX or FX combined with Gef treatment. PC9 xenograft model was established to explore the anti-tumor effect of FX or combined with Gef. Immunohistochemistry staining assay and immunofluorescence staining assay were used to reveal the effects of FX on lung cancer cell proliferation and apoptosis. RESULTS: FX was able to significantly inhibit lung cancer cells migration and invasion in vitro. FX suppressed the expressions of Snail, Twist, Fibronectin, N-cadherin, MMP-2, PI3K, p-AKT and NF-κB, and increased the expression of TIMP-2. Furthermore, knockdown of TIMP-2 attenuated FX-mediated invasion inhibition. Additionally, we demonstrated that FX inhibited lung cancer cells metastasis in vivo. The anti-metastatic effects of FX on lung cancer cells might be attributed to inhibition of EMT and PI3K/AKT/NF-κB pathway. We further demonstrated that the anti-tumor activity of FX was not only limited to the drug sensitive cell lines, but also prominent on lung cancer cells with Gef resistant phenotype. Furthermore, in vivo xenograft assay confirmed that FX inhibited tumor growth and enhanced the sensitivity of lung cancer cells to Gef and this effect may be due to inhibition of tumor cell proliferation and activation of apoptosis. CONCLUSION: Collectively, our findings suggested that FX suppresses metastasis of lung cancer cells and overcomes EGFR TKIs resistance. Thus, FX is worthy of further investigation as a drug candidate for the treatment of lung cancer.

Synergistic effects of UVA irradiation and phlorotannin extracts of Laminaria japonica on properties of grass carp myofibrillar protein gel.

BACKGROUND: Oxidized phlorotannin can be used as a protein crosslinking agent to produce high-quality fish gel products. Phlorotannin can be easily induced to form quinone compounds in an oxidizing environment, while o-quinone has been proven to be a reactive, electrophilic intermediate that easily reacts with proteins to form rigid molecular crosslinking networks. The objective of this study was to investigate the synergistic effects of ultraviolet A (UVA) irradiation (1 h, 15 W m-2 ) and various concentrations of Laminaria japonica phlorotannin extracts (PTE) on the gel properties of grass carp myofibrillar protein (MP). RESULTS: UVA treatment and PTE could synergistically improve the MP gel properties more than PTE alone (P < 0.05). At 625 mmol kg-1 MP PTE alone, the gel strength and cooking yield reached 3.10 ± 0.16 g cm and 47.45 ± 0.35%, respectively, while with the same level of PTE plus UVA they became 4.26 ± 0.19 g cm and 53.89 ± 1.54%, respectively. The three-dimensional network structure of the gel (with PTE + UVA) showed higher connectivity and tightness than that of the control group (no treatment). CONCLUSIONS: The synergistic effects of PTE and UVA could effectively induce crosslinking of grass carp MP, which could lead to an improvement of MP gel quality. These findings would provide a new technical approach to produce high-quality protein gel products in the fish processing industry. © 2020 Society of Chemical Industry.

Brown Seaweeds for the Management of Metabolic Syndrome and Associated Diseases.

Metabolic syndrome is characterized by the coexistence of different metabolic disorders which increase the risk of developing type 2 diabetes mellitus and cardiovascular diseases. Therefore, metabolic syndrome leads to a reduction in patients' quality of life as well as to an increase in morbidity and mortality. In the last few decades, it has been demonstrated that seaweeds exert multiple beneficial effects by virtue of their micro- and macronutrient content, which could help in the management of cardiovascular and metabolic diseases. This review aims to provide an updated overview on the potential of brown seaweeds for the prevention and management of metabolic syndrome and its associated diseases, based on the most recent evidence obtained from in vitro and in vivo preclinical and clinical studies. Owing to their great potential for health benefits, brown seaweeds are successfully used in some nutraceuticals and functional foods for treating metabolic syndrome comorbidities. However, some issues still need to be tackled and deepened to improve the knowledge of their ADME/Tox profile in humans, in particular by finding validated indexes of their absorption and obtaining reliable information on their efficacy and long-term safety.

Inhibitory Effects of Laminaria japonica Fucoidans Against Noroviruses.

Norovirus is the leading cause of nonbacterial foodborne disease outbreaks. Human noroviruses (HuNoVs) bind to histo-blood group antigens as the host receptor for infection. In this study, the inhibitory effects of fucoidans from brown algae, Laminaria japonica (LJ), Undaria pinnatifida and Undaria pinnatifida sporophyll, were evaluated against murine norovirus (MNoV), feline calicivirus (FCV) and HuNoV. Pretreatment of MNoV or FCV with the fucoidans at 1 mg/mL showed high antiviral activities, with 1.1 average log reductions of viral titers in plaque assays. They also showed significant inhibition on the binding of the P domains of HuNoV GII.4 and GII.17 to A- or O-type saliva and the LJ fucoidan was the most effective, reaching 54-72% inhibition at 1 mg/mL. In STAT1-/- mice infected with MNoV, oral administration of the LJ fucoidan, composed of mainly sulfated fucose and minor amounts of glucose and galactose, improved the survival rates of mice and significantly reduced the viral titers in their feces. Overall, these results provide the LJ fucoidan can be used to reduce NoV outbreaks.

Preventive Effects of Three Polysaccharides on the Oxidative Stress Induced by Acrylamide in a Saccharomyces cerevisiae Model.

Saccharomyces cerevisiae was used as a model to explore the preventive effect of two marine polysaccharides separately derived from Sepia esculenta ink (SIP) and Laminaria japonica (FL) as well as one terrestrial polysaccharides from Eleocharis tuberosa peel (WCPP) on toxic injury induced by acrylamide (AA). The growth of yeast was evaluated by kinetics indexes including doubling time, lag phase and maximum proliferation density. Meanwhile, intracellular redox state was determined by contents of MDA and GSH, and SOD activity. The results showed that AA inhibited yeast growth and destroyed the antioxidant defense system. Supplement with polysaccharides, the oxidative damage of cells was alleviated. According to the growth recovery of yeast, FL and WCPP had similar degree of capacity against AA associated cytotoxicity, while SIP was 1.5~2 folds as strong as FL and WCPP. SIP and FL significantly reduced production of MDA by AA administration. Moreover, SIP, FL and WCPP increased SOD activity and repressed GSH depletion caused by AA.

Optimisation of Ultrasound Frequency, Extraction Time and Solvent for the Recovery of Polyphenols, Phlorotannins and Associated Antioxidant Activity from Brown Seaweeds.

This study investigates ultrasound assisted extraction (UAE) process parameters (time, frequency and solvent) to obtain high yields of phlorotannins, flavonoids, total phenolics and associated antioxidant activities from 11 brown seaweed species. Optimised UAE conditions (35 kHz, 30 min and 50% ethanol) significantly improved the extraction yield from 1.5-fold to 2.2-fold in all seaweeds investigated compared to solvent extraction. Using ultrasound, the highest recovery of total phenolics (TPC: 572.3 ± 3.2 mg gallic acid equivalent/g), total phlorotannins (TPhC: 476.3 ± 2.2 mg phloroglucinol equivalent/g) and total flavonoids (TFC: 281.0 ± 1.7 mg quercetin equivalent/g) was obtained from Fucus vesiculosus seaweed. While the lowest recovery of TPC (72.6 ± 2.9 mg GAE/g), TPhC (50.3 ± 2.0 mg PGE/g) and TFC (15.2 ± 3.3 mg QE/g) was obtained from Laminaria digitata seaweed. However, extracts from Fucus serratus obtained by UAE exhibited the strongest 1,1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging activity (29.1 ± 0.25 mg trolox equivalent/g) and ferric reducing antioxidant power (FRAP) value (63.9 ± 0.74 mg trolox equivalent/g). UAE under optimised conditions was an effective, low-cost and eco-friendly technique to recover biologically active polyphenols from 11 brown seaweed species.

The Antithrombotic Effects of Low Molecular Weight Fragment from Enzymatically Modified of Laminaria Japonica Polysaccharide.

BACKGROUND Laminaria japonica polysaccharide (LJP), a fucose enriched sulfated polysaccharide has been demonstrated to have excellent anticoagulant and antithrombotic activities. However, the antithrombotic effect of low molecular weight polysaccharide from enzymatically modified of LJP (LMWEP) remains unknown. MATERIAL AND METHODS LMWEP was prepared by fucoidanase enzymatic hydrolysis, and the antithrombotic and anticoagulant activities, and the underlying mechanism were investigated thoroughly. Rats were randomly divided into 6 groups (8 rats in each group): the blank control group, the blank control group treated with LMWEP (20 mg/kg), the model group, the model group treated with heparin (2 mg/kg), the model group treated with LJP (20 mg/kg), and the model group treated with LMWEP (20 mg/kg). After 7 days of intravenous administration, blood was collected for biochemical parameters examinations. RESULTS LMWEP increased the activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), 6-keto prostaglandin F1alpha (6-Keto-PGF1alpha), and endothelial nitric oxide synthase (eNOS). In addition, LMWEP decreased fibrinogen (FIB), endothelin-1 (ET-1), thromboxane B2 (TXB2), erythrocyte sedimentation rate (ESR), and hematocrit (HCT). CONCLUSIONS LMWEP, an enzymatically modified fragment with a molecular weight of 25.8 kDa, is a potential antithrombotic candidate for treatment of thrombosis related diseases.

Acid-free preparation and characterization of kelp (Laminaria japonica) nanocelluloses and their application in Pickering emulsions.

Cellulose nanofibers (CNFs) from kelp were prepared by cellulase treatment with lengths greater than 3 µm. CNFs were further oxidized by TEMPO-oxidized system, and the lengths of the oxidized CNFs (TEMPO-CNFs) were 0.6-1 µm. AFM and TEM images showed that intertwined CNFs fibers were divided into individual nanofibrils. The crystallinity of TEMPO-CNFs increased to 66.5 %. TGA analysis indicated that TEMPO-CNFs were more sensitive to temperature than cellulose and CNFs. FT-IR spectra revealed no changes in the basic cellulose structures of CNFs and TEMPO-CNFs. In the sunflower oil/water (20/80, v/v) model emulsions, the oil droplet sizes were less than 20 µm in CNFs emulsions, which became smaller in TEMPO-CNFs emulsions. Delamination was found in CNFs emulsions after three days of storage. Addition of NaCl increased the volumes of TEMPO-CNFs emulsions but enlarged the oil droplets sizes. TEMPO-CNFs emulsions had the largest volume with smallest and most homogeneous oil droplets at pH 3. TEMPO-CNFs emulsions showed good stability after storage for 30 days. Further, TEMPO-CNFs could also emulsify 50 % (v/v) of sunflower oil. All these results indicated that TEMPO-CNFs can be used in preparing Pickering emulsions.

Synergistic Antibacterial Efficacies of Chlorhexidine Digluconate or Protamine Sulfate Combined with Laminaria japonica or Rosmarinus officinalis Extracts against Streptococcus mutans.

Chlorhexidine digluconate inhibits oral bacteria and the formation of dental plaque. Protamine sulfate, a polycationic protein, exerts antibacterial activity by altering the cell wall of bacteria. Extracts of Laminaria japonica and Rosmarinus officinalis display antimicrobial effects against oral pathogens. The purpose of this study was to investigate the synergistic effect of chlorhexidine digluconate and protamine sulfate on the inhibitory activity of L. japonica and R. officinalis extracts against Streptococcus mutans, a major etiological agent for dental caries. Minimal inhibitory concentrations (MICs) of chlorhexidine digluconate, protamine sulfate, and L. japonica and R. officinalis extracts were determined by broth dilution method. Synergistic effect of chlorhexidine digluconate or protamine sulfate and extracts of L. japonica or R. officinalis was determined by fractional inhibitory concentration index (FIC). FIC demonstrated the synergistic effects of the different combinations of antibacterial agents. In this study, the use of sub-MIC of chlorhexidine digluconate or protamine sulfate with sub-MIC of L. japonica and R. officinalis extracts resulted in synergistic inhibitory effects of these antibacterial agents except for chlorhexidine digluconate and L. japonica combination.

Effects of whole plant brown algae (Laminaria japonica) on zootechnical performance, apparent total tract digestibility, faecal characteristics and blood plasma urea in weaned piglets.

Two trials were conducted with 48 newly weaned piglets (28 d old) each 8.6 ± 0.05 kg to study how Laminaria japonica plants (LJ) affect zootechnical performance, feed conversion and the apparent total tract digestibility (ATTD) of crude nutrients. All basal diets consisted of cereals, soybean meal, skim milk powder and premixes according to recommendations (no growth promoters or enzymes). For Trial 1, piglets from 16 litters (50% male-castrated, 50% female) were assigned to three treatment groups (n = 16) in a completely randomised block design. Groups received either 2.5% supplementation with sun dried (SD) or drum dried (DD) LJ powder or 2.5% of diatomaceous earth (control). For Trial 2, piglets from 12 litters received either 5% of diatomaceous earth (control) or one of three mixtures of diatomaceous earth + DD LJ powder (3.3%+1.7%, 1.7%+3.3% or 0.0%+5%; n = 12). Data collection included zootechnical performance, faecal consistency, blood plasma urea (Trial 1 and 2) and ATTD (Trial 2). Metabolisable energy (ME) of DD LJ and diets in Trial 2 was estimated using digestible nutrients. Statistical analysis included two-way ANOVA (treatment, block) and mixed linear regression. During both trials, LJ at dosages ≥2.5% significantly reduced feed:gain ratio compared to control (p ≤ 0.0001, = 0.01 for Trial 1, Trial 2) irrespective of the drying method. ATTD from Trial 2 significantly increased digestibilities of dry matter (DM) and crude ash (CA) (p ≤ 0.01) and significantly decreased digestibilities of organic matter and crude fibre in animals fed ≥3.33% DD LJ (p = 0.01). Fractional digestibility of the DD LJ resulted in limited ME of ~9.3 ± 2.5 MJ/kg DM. Dietary conversion ratios of ME and digestible DM of DD LJ diets from Trial 2 decreased linearly with increasing algal supplementation (R2 = 0.93, 0.94 and pslope = 0.002, 0.002 for MCR, DCR). In conclusion, dried LJ powder was included up to 5% into diets without impairing zootechnical performance. The improved feed conversion in the presence of LJ was partly due to slightly higher ME within the algae diets compared to control. However, piglets receiving LJ during Trial 2 needed significantly lower dietary ME and digestible DM to maintain growth performance. Thus, LJ exerted a performance enhancing effect on weaned piglets. The precise mode-of-action is yet unclear.

Protective effects of a mixed plant extracts derived from Astragalus membranaceus and Laminaria japonica on PTU-induced hypothyroidism and liver damages.

Protective effects of a mixed hot water extracts of Astragalus membranaceus (AWE) and Laminaria japonica (LWE), AWE: LWE 85:15 (g/g; AL mix), were investigated against propylthiouracil (PTU)-induced hypothyroidism in rats. Rats were challenged with PTU, resulting in, increased thyroid gland weight, decreased liver weight and antioxidant activities, reduced serum tri-iodothyronine and thyroxine levels with increased thyroid stimulating hormone levels, and elevated serum aspartate aminotransferase level. However, orally administered AL mix with 100, 200, and 400 mg kg-1  day-1 , significantly inhibited such abnormalities, dose-dependently. Moreover, PTU-induced abnormal histological architecture of the rat thyroid gland and liver were also significantly ameliorated by an AL mix. The results suggested that, therapeutic use of AL mix for treating hypothyroidism can be characterized by its diversified active ingredients particularly iodine and ferulic acid as confirmed by phytochemical analyses. PRACTICAL APPLICATIONS: The AL mix has synergistic effects in modulating thyroid hormone synthesis and preventing liver damages in PTU-induced hypothyroid rats. These effects of AL mix are mainly related to its richness specifically in iodine and ferulic acid. The growing interests of iodine and ferulic acid in AL mix are principally due to their beneficial effects in releasing sufficient thyroid hormones in hypothyroid conditions and promoting liver-protective functions through its antioxidant and anti-inflammatory potentials, respectively. Moreover, the results of AL mix are well-matched with the effects of standard drug levothyroxine in the present study. Therefore, appropriate dosage of AL mix will be promising as new medicinal food for preventing thyroid dysfunctions and its related liver damages.

Laminaria japonica Extract Enhances Intestinal Barrier Function by Altering Inflammatory Response and Tight Junction-Related Protein in Lipopolysaccharide-Stimulated Caco-2 Cells.

In the normal physiological state, intestinal epithelial cells act as a defensive frontline of host mucosal immunity to tolerate constant exposure to external stimuli. In this study, we investigated the potential anti-inflammatory and gut permeability protective effects of Laminaria japonica (LJ) water extract (LJE) and three types of fermented Laminaria japonica water extracts (LJE-F1, LJE-F2, and LJE-F3) in lipopolysaccharide (LPS)-stimulated Caco-2, human intestinal epithelial cells. All four extracts significantly decreased the production of nitric oxide and interleukin-6 induced by LPS stimulus. In addition, LJE and the three types of LJE-Fs also inhibited LPS-induced loss of monolayer permeability, as assessed by changes in transepithelial electrical resistance. All four LJ extracts significantly prevented the inhibition of the protein levels of occludin, whereas LJE, LJE-F1, and LJE-F3 significantly attenuated the reduction in phosphorylation of adenosine monophosphate-activated protein kinase compared with the LPS-treated group in Caco-2 cells. In conclusion, LJE and its fermented water extracts appear to have potential gut health-promoting effects by reducing inflammation and partially regulating the tight junction-related proteins in human intestinal epithelial cells. Thus, additional studies are warranted to evaluate Laminaria japonica as a therapeutic agent for inflammatory bowel diseases.

In Vitro Digestion and Fermentation of Three Polysaccharide Fractions from Laminaria japonica and Their Impact on Lipid Metabolism-Associated Human Gut Microbiota.

Our previous study has proved that the three polysaccharide fractions from L. japonica (LP-A4, LP-A6, and LP-A8) had significantly different structure characterization. Herein, we conducted in vitro simulated digestion and fermentation to study the digestive mechanism of LP-As. The results of gastrointestinal digestion indicated that LP-A6 and LP-A8 would be easier to trap the enzyme molecules for their denser interconnected macromolecule network compared with LP-A4. Fermentation of LP-As by human gut microbiota, especially for LP-A8, generated a large amount of short-chain fatty acids (SCFAs), which could upregulate the abundance of Firmicutes ( Lachnoclostridium and Eubacterium). The high content of sulfate and highly branched sugar residue of LP-A8 might help it be easily used by Firmicutes in gut microbiota of hyperlipidemic patients. Functional analysis revealed that the increased metabolic activities of glycerophospholipid metabolism, ether lipid metabolism, and fatty acid metabolism induced by LP-A8 treatment were closely associated with metabolic syndromes and hyperlipidemia.

The Inhibitory Effect of Propylene Glycol Alginate Sodium Sulfate on Fibroblast Growth Factor 2-Mediated Angiogenesis and Invasion in Murine Melanoma B16-F10 Cells In Vitro.

Melanoma is one of the most malignant and aggressive types of cancer worldwide. Fibroblast growth factor 2 (FGF2) is one of the critical regulators of melanoma angiogenesis and metastasis; thus, it might be an effective anti-cancer strategy to explore FGF2-targeting drug candidates from existing drugs. In this study, we evaluate the effect of the marine drug propylene glycol alginate sodium sulfate (PSS) on FGF2-mediated angiogenesis and invasion. The data shows that FGF2 selectively bound to PSS with high affinity. PSS inhibited FGF2-mediated angiogenesis in a rat aortic ring model and suppressed FGF2-mediated invasion, but not the migration of murine melanoma B16-F10 cells. The further mechanism study indicates that PSS decreased the expression of activated matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and also suppressed their activity. In addition, PSS was found to decrease the level of Vimentin in B16-F10 cells, which is known to participate in the epithelial-mesenchymal transition. Notably, PSS did not elicit any changes in cancer cell viability. Based on the results above, we conclude that PSS might be a potential drug to regulate the tumor microenvironment in order to facilitate the recovery of melanoma patients.