Marine Drugs

2024

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28 pages, 3065 KiB

Open AccessReview

Biomarkers and Seaweed-Based Nutritional Interventions in Metabolic Syndrome: A Comprehensive Review

by Ana Valado, Margarida Cunha and Leonel Pereira

Mar. Drugs 2024, 22(12), 550; https://doi.org/10.3390/md22120550 - 4 Dec 2024

Viewed by 858

Abstract

Metabolic Syndrome (MetS) is a complex, multifactorial condition characterized by risk factors such as abdominal obesity, insulin resistance, dyslipidemia and hypertension, which significantly contribute to the development of cardiovascular disease (CVD), the leading cause of death worldwide. Early identification and effective monitoring of [...] Read more.

Metabolic Syndrome (MetS) is a complex, multifactorial condition characterized by risk factors such as abdominal obesity, insulin resistance, dyslipidemia and hypertension, which significantly contribute to the development of cardiovascular disease (CVD), the leading cause of death worldwide. Early identification and effective monitoring of MetS is crucial for preventing serious cardiovascular complications. This article provides a comprehensive overview of various biomarkers associated with MetS, including lipid profile markers (triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio), inflammatory markers (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), leptin/adiponectin ratio, omentin and fetuin-A/adiponectin ratio), oxidative stress markers (lipid peroxides, protein and nucleic acid oxidation, gamma-glutamyl transferase (GGT), uric acid) and microRNAs (miRNAs) such as miR-15a-5p, miR5-17-5p and miR-24-3p. Additionally, this review highlights the importance of biomarkers in MetS and the need for advancements in their identification and use for improving prevention and treatment. Seaweed therapy is also discussed as a significant intervention for MetS due to its rich content of fiber, antioxidants, minerals and bioactive compounds, which help improve cardiovascular health, reduce inflammation, increase insulin sensitivity and promote weight loss, making it a promising nutritional strategy for managing metabolic and cardiovascular health. Full article

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15 pages, 2978 KiB

Open AccessArticle

Initial Exploration of the In Vitro Activation of GLP-1 and GIP Receptors and Pancreatic Islet Cell Protection by Salmon-Derived Bioactive Peptides

by Crawford Currie, Christian Bjerknes and Bomi Framroze

Mar. Drugs 2024, 22(11), 490; https://doi.org/10.3390/md22110490 - 30 Oct 2024

Viewed by 1139

Abstract

This study examines the in vitro effects of a soluble protein hydrolysate (SPH) derived from Atlantic salmon (Salmo salar) on incretin receptor activity and pancreatic islet cell protection to explore the mechanisms underlying SPH’s observed benefits on weight loss and metabolic health in [...] Read more.

This study examines the in vitro effects of a soluble protein hydrolysate (SPH) derived from Atlantic salmon (Salmo salar) on incretin receptor activity and pancreatic islet cell protection to explore the mechanisms underlying SPH’s observed benefits on weight loss and metabolic health in overweight individuals. SPH demonstrated a dose-dependent enhancement of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) receptor activity, with significant increases of 2.4-fold (p < 0.05) and 2.6-fold (p < 0.01) at 10 mg/mL, respectively, compared to the control. Pancreatic islet cell assays showed a substantial proliferation effect, with up to a 57% increase at 50 µL/well, indicating potential protective properties against inflammation-induced cell loss. Notably, the smallest SPH peptide fraction (<1000 Da) exhibited GLP-1 agonist activity comparable to semaglutide, a widely used therapeutic agent, underscoring SPH’s potential efficacy in modulating metabolic pathways. These results suggest that SPH not only enhances key incretin signaling but also promotes islet cell health, positioning it as a promising dietary intervention to improve age-related metabolic health, including the weight gain and underlying adverse metabolic changes frequently encountered through the menopause. Full article

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25 pages, 7587 KiB

Open AccessArticle

Exploring Marine-Derived Compounds: In Silico Discovery of Selective Ketohexokinase (KHK) Inhibitors for Metabolic Disease Therapy

by Mansour S. Alturki

Mar. Drugs 2024, 22(10), 455; https://doi.org/10.3390/md22100455 - 3 Oct 2024

Viewed by 3348

Abstract

The increasing prevalence of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes, poses significant global health challenges. Ketohexokinase (KHK), an enzyme crucial in fructose metabolism, is a potential therapeutic target due to its role in these conditions. This [...] Read more.

The increasing prevalence of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes, poses significant global health challenges. Ketohexokinase (KHK), an enzyme crucial in fructose metabolism, is a potential therapeutic target due to its role in these conditions. This study focused on the discovery of selective KHK inhibitors using in silico methods. We employed structure-based drug design (SBDD) and ligand-based drug design (LBDD) approaches, beginning with molecular docking to identify promising compounds, followed by induced-fit docking (IFD), molecular mechanics generalized Born and surface area continuum solvation (MM-GBSA), and molecular dynamics (MD) simulations to validate binding affinities. Additionally, shape-based screening was conducted to assess structural similarities. The findings highlight several potential inhibitors with favorable ADMET profiles, offering promising candidates for further development in the treatment of fructose-related metabolic disorders. Full article

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2023

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16 pages, 4281 KiB

Open AccessArticle

Laminarin Reduces Cholesterol Uptake and NPC1L1 Protein Expression in High-Fat Diet (HFD)-Fed Mice

by Zhuoqian He, Zhongyin Zhang, Pengfei Xu, Verena M. Dirsch, Limei Wang and Kewei Wang

Mar. Drugs 2023, 21(12), 624; https://doi.org/10.3390/md21120624 - 29 Nov 2023

Cited by 1 | Viewed by 2337

Abstract

Aberrantly high dietary cholesterol intake and intestinal cholesterol uptake lead to dyslipidemia, one of the risk factors for cardiovascular diseases (CVDs). Based on previous studies, laminarin, a polysaccharide found in brown algae, has hypolipidemic activity, but its underlying mechanism has not been elucidated. [...] Read more.

Aberrantly high dietary cholesterol intake and intestinal cholesterol uptake lead to dyslipidemia, one of the risk factors for cardiovascular diseases (CVDs). Based on previous studies, laminarin, a polysaccharide found in brown algae, has hypolipidemic activity, but its underlying mechanism has not been elucidated. In this study, we investigated the effect of laminarin on intestinal cholesterol uptake in vitro, as well as the lipid and morphological parameters in an in vivo model of high-fat diet (HFD)-fed mice, and addressed the question of whether Niemann–Pick C1-like 1 protein (NPC1L1), a key transporter mediating dietary cholesterol uptake, is involved in the mechanistic action of laminarin. In in vitro studies, BODIPY-cholesterol-labeled Caco-2 cells were examined using confocal microscopy and a fluorescence reader. The results demonstrated that laminarin inhibited cholesterol uptake into Caco-2 cells in a concentration-dependent manner (EC₅₀ = 20.69 μM). In HFD-fed C57BL/6J mice, laminarin significantly reduced the serum levels of total cholesterol (TC), total triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). It also decreased hepatic levels of TC, TG, and total bile acids (TBA) while promoting the excretion of fecal cholesterol. Furthermore, laminarin significantly reduced local villous damage in the jejunum of HFD mice. Mechanistic studies revealed that laminarin significantly downregulated NPC1L1 protein expression in the jejunum of HFD-fed mice. The siRNA-mediated knockdown of NPC1L1 attenuated the laminarin-mediated inhibition of cholesterol uptake in Caco-2 cells. This study suggests that laminarin significantly improves dyslipidemia in HFD-fed mice, likely by reducing cholesterol uptake through a mechanism that involves the downregulation of NPC1L1 expression. Full article

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2022

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17 pages, 4358 KiB

Open AccessArticle

A Nutraceutical Formulation Containing Brown Algae Reduces Hepatic Lipid Accumulation by Modulating Lipid Metabolism and Inflammation in Experimental Models of NAFLD and NASH

by Daniela Gabbia, Marco Roverso, Ilaria Zanotto, Martina Colognesi, Katia Sayaf, Samantha Sarcognato, Diletta Arcidiacono, Alice Zaramella, Stefano Realdon, Nicola Ferri, Maria Guido, Francesco Paolo Russo, Sara Bogialli, Maria Carrara and Sara De Martin

Mar. Drugs 2022, 20(9), 572; https://doi.org/10.3390/md20090572 - 8 Sep 2022

Cited by 6 | Viewed by 3178

Abstract

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models [...] Read more.

Recently, some preclinical and clinical studies have demonstrated the ability of brown seaweeds in reducing the risk factors for metabolic syndrome. Here, we analyzed the beneficial effect of a nutraceutical formulation containing a phytocomplex extracted from seaweeds and chromium picolinate in animal models of liver steatosis of differing severities (rats with non-alcoholic fatty liver disease (NAFLD) and its complication, non-alcoholic steatohepatitis (NASH)). This treatment led to a significant drop in hepatic fat deposition in both models (p < 0.01 vs. untreated animals), accompanied by a reduction in plasma inflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and C reactive protein, and myeloperoxidase expression in liver tissue. Furthermore, a modulation of the molecular pathways involved in lipid metabolism and storage was demonstrated, since we observed the significant reduction of the mRNA levels of fatty acid synthase, diacylglycerol acyltransferases, the sterol-binding protein SREBP-1, and the lipid transporter perilipin-2, in both treated NAFLD and NASH rats in comparison to untreated ones. In conclusion, this nutraceutical product was effective in reducing liver steatosis and showed further beneficial effects on hepatic inflammation and glycemic control, which were particularly evident in rats characterized by a more severe condition, thus representing a therapeutic option for the treatment of NAFLD and NASH patients. Full article

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2021

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15 pages, 2998 KiB

Open AccessArticle

Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes

by Massimo Genovese, Concetta Imperatore, Marcello Casertano, Anna Aiello, Francesco Balestri, Lucia Piazza, Marialuisa Menna, Antonella Del Corso and Paolo Paoli

Mar. Drugs 2021, 19(10), 535; https://doi.org/10.3390/md19100535 - 24 Sep 2021

Cited by 15 | Viewed by 3204

Abstract

An in-depth study on the inhibitory mechanism on protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) enzymes, including analysis of the insulin signalling pathway, of phosphoeleganin, a marine-derived phosphorylated polyketide, was achieved. Phosphoeleganin was demonstrated to inhibit both enzymes, acting respectively as [...] Read more.

An in-depth study on the inhibitory mechanism on protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) enzymes, including analysis of the insulin signalling pathway, of phosphoeleganin, a marine-derived phosphorylated polyketide, was achieved. Phosphoeleganin was demonstrated to inhibit both enzymes, acting respectively as a pure non-competitive inhibitor of PTP1B and a mixed-type inhibitor of AR. In addition, in silico docking analyses to evaluate the interaction mode of phosphoeleganin with both enzymes were performed. Interestingly, this study showed that phosphoeleganin is the first example of a dual inhibitor polyketide extracted from a marine invertebrate, and it could be used as a versatile scaffold structure for the synthesis of new designed multiple ligands. Full article

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17 pages, 3685 KiB

Open AccessArticle

Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis

by Ping-Hsiao Shih, Sheng-Jie Shiue, Chun-Nan Chen, Sheng-Wei Cheng, Hsin-Yi Lin, Li-Wei Wu and Ming-Shun Wu

Mar. Drugs 2021, 19(3), 148; https://doi.org/10.3390/md19030148 - 12 Mar 2021

Cited by 49 | Viewed by 7750

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRG^TM cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD. Full article

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14 pages, 2184 KiB

Open AccessArticle

Effects of Ethanol Extracts from Grateloupia elliptica, a Red Seaweed, and Its Chlorophyll Derivative on 3T3-L1 Adipocytes: Suppression of Lipid Accumulation through Downregulation of Adipogenic Protein Expression

by Hyo-Geun Lee, Yu-An Lu, Jun-Geon Je, Thilina U. Jayawardena, Min-Cheol Kang, Seung-Hong Lee, Tae-Hee Kim, Dae-Sung Lee, Jeong-Min Lee, Mi-Jin Yim, Hyun-Soo Kim and You-Jin Jeon

Mar. Drugs 2021, 19(2), 91; https://doi.org/10.3390/md19020091 - 4 Feb 2021

Cited by 18 | Viewed by 5031

Abstract

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular [...] Read more.

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity. Full article

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20 pages, 1381 KiB

Open AccessReview

Fucoidan Structure and Its Impact on Glucose Metabolism: Implications for Diabetes and Cancer Therapy

by Blessing Mabate, Chantal Désirée Daub, Samkelo Malgas, Adrienne Lesley Edkins and Brett Ivan Pletschke

Mar. Drugs 2021, 19(1), 30; https://doi.org/10.3390/md19010030 - 11 Jan 2021

Cited by 57 | Viewed by 7778

Abstract

Fucoidans are complex polysaccharides derived from brown seaweeds which consist of considerable proportions of L-fucose and other monosaccharides, and sulphated ester residues. The search for novel and natural bioproduct drugs (due to toxicity issues associated with chemotherapeutics) has led to the extensive study [...] Read more.

Fucoidans are complex polysaccharides derived from brown seaweeds which consist of considerable proportions of L-fucose and other monosaccharides, and sulphated ester residues. The search for novel and natural bioproduct drugs (due to toxicity issues associated with chemotherapeutics) has led to the extensive study of fucoidan due to reports of it having several bioactive characteristics. Among other fucoidan bioactivities, antidiabetic and anticancer properties have received the most research attention in the past decade. However, the elucidation of the fucoidan structure and its biological activity is still vague. In addition, research has suggested that there is a link between diabetes and cancer; however, limited data exist where dual chemotherapeutic efforts are elucidated. This review provides an overview of glucose metabolism, which is the central process involved in the progression of both diseases. We also highlight potential therapeutic targets and show the relevance of fucoidan and its derivatives as a candidate for both cancer and diabetes therapy. Full article

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2020

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8 pages, 1939 KiB

Open AccessArticle

Fucus vesiculosus and Ascophyllum nodosum Ameliorate Liver Function by Reducing Diet-Induced Steatosis in Rats

by Daniela Gabbia, Miriam Saponaro, Samantha Sarcognato, Maria Guido, Nicola Ferri, Maria Carrara and Sara De Martin

Mar. Drugs 2020, 18(1), 62; https://doi.org/10.3390/md18010062 - 17 Jan 2020

Cited by 20 | Viewed by 4224

Abstract

The Asian coastal communities have used the brown seaweeds Fucus vesiculosus and Ascophyllum nodosum since ancient times. Recently, some in vitro and in vivo studies have demonstrated their abilities in reducing risk factors for metabolic syndrome. Here, we analyzed the protective effect of [...] Read more.

The Asian coastal communities have used the brown seaweeds Fucus vesiculosus and Ascophyllum nodosum since ancient times. Recently, some in vitro and in vivo studies have demonstrated their abilities in reducing risk factors for metabolic syndrome. Here, we analyzed the protective effect of a phytocomplex extracted from these seaweeds on the deposition of fat in the liver after the administration of a high-fat diet (HFD) to rats for five weeks. The administration of F. vesiculosus and A. nodosum led to significant reductions in microvescicular steatosis and plasma biochemical and lipid parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total and conjugated bilirubin, and triglycerides. Furthermore, the postprandial glycemic peak was delayed and significantly reduced (p < 0.01) by the algal extract administration. In conclusion, this extract is effective in reducing microvescicular steatosis and improving glycemic control, thereby lowering the risk of nonalcoholic fatty liver disease, obesity, and diabetes, diseases related to the consumption of fat and sugar-enriched diets. Full article

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2019

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15 pages, 6319 KiB

Open AccessArticle

Chitosan Oligosaccharide Attenuates Nonalcoholic Fatty Liver Disease Induced by High Fat Diet through Reducing Lipid Accumulation, Inflammation and Oxidative Stress in C57BL/6 Mice

by Wenjing Tao, Wanjing Sun, Lujie Liu, Geng Wang, Zhiping Xiao, Xun Pei and Minqi Wang

Mar. Drugs 2019, 17(11), 645; https://doi.org/10.3390/md17110645 - 16 Nov 2019

Cited by 71 | Viewed by 4869

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease closely associated with metabolic syndrome, but there are no validated pharmacological therapies. The aim of this study was to investigate the effect of chitosan oligosaccharide (COS) on NAFLD. Mice were [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease closely associated with metabolic syndrome, but there are no validated pharmacological therapies. The aim of this study was to investigate the effect of chitosan oligosaccharide (COS) on NAFLD. Mice were fed either a control diet or a high-fat diet (HFD) with or without COS (200 or 400 mg/kg body weight (BW)) by oral gavage for seven weeks. Administration with COS significantly lowered serum lipid levels in the HFD-fed mice. The hepatic lipid accumulation was significantly decreased by COS, which was attributed to decreased expressions of lipogenic genes and increased expressions of fatty β-oxidation-related genes. Moreover, pro-inflammatory cytokines, neutrophils infiltration, and macrophage polarization were decreased by COS in the liver. Furthermore, COS ameliorated hepatic oxidative stress by activating the nuclear factor E2-related factor 2 (Nrf2) pathway and upregulating gene expressions of antioxidant enzymes. These beneficial effects were mediated by the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Therefore, COS might be a potent dietary supplement to ameliorate NAFLD. Full article

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11 pages, 1576 KiB

Open AccessArticle

Anti-Obesity Effect of Diphlorethohydroxycarmalol Isolated from Brown Alga Ishige okamurae in High-Fat Diet-Induced Obese Mice

by Yuling Ding, Lei Wang, SeungTae Im, Ouibo Hwang, Hyun-Soo Kim, Min-Cheol Kang and Seung-Hong Lee

Mar. Drugs 2019, 17(11), 637; https://doi.org/10.3390/md17110637 - 10 Nov 2019

Cited by 26 | Viewed by 4322

Abstract

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current [...] Read more.

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases. Full article

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39 pages, 19585 KiB

Open AccessReview

Antihypertensive and Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Fish as Potential Cardioprotective Compounds

by Soheila Abachi, Laurent Bazinet and Lucie Beaulieu

Mar. Drugs 2019, 17(11), 613; https://doi.org/10.3390/md17110613 - 29 Oct 2019

Cited by 83 | Viewed by 7286

Abstract

The term metabolic/cardiometabolic/insulin resistance syndrome could generally be defined as the co-occurrence of several risk factors inclusive of systemic arterial hypertension. Not only that organizations, such as the world health organization (WHO) have identified high blood pressure as one of the main risk [...] Read more.

The term metabolic/cardiometabolic/insulin resistance syndrome could generally be defined as the co-occurrence of several risk factors inclusive of systemic arterial hypertension. Not only that organizations, such as the world health organization (WHO) have identified high blood pressure as one of the main risk factors of the cardiometabolic syndrome, but there is also a link between the occurrence of insulin resistance/impaired glucose tolerance and hypertension that would consequently lead to type-2 diabetes (T2D). Hypertension is medicated by various classes of synthetic drugs; however, severe or mild adverse effects have been repeatedly reported. To avoid and reduce these adverse effects, natural alternatives, such as bioactive peptides derived from different sources have drawn the attention of researchers. Among all types of biologically active peptides inclusive of marine-derived ones, this paper’s focus would solely be on fish and fishery by-processes’ extracted peptides and products. Isolation and fractionation processes of these products alongside their structural, compositional and digestion stability characteristics have likewise been briefly discussed to better address the structure-activity relationship, expanding the reader’s knowledge on research and discovery trend of fish antihypertensive biopeptides. Furthermore, drug-likeness of selected biopeptides was predicted by Lipinski’s rules to differentiate a drug-like biopeptide from nondrug-like one. Full article

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14 pages, 1398 KiB

Open AccessArticle

Pyrogallol-Phloroglucinol-6,6-Bieckol Alleviates Obesity and Systemic Inflammation in a Mouse Model by Reducing Expression of RAGE and RAGE Ligands

by Junwon Choi, Seyeon Oh, Myeongjoo Son and Kyunghee Byun

Mar. Drugs 2019, 17(11), 612; https://doi.org/10.3390/md17110612 - 28 Oct 2019

Cited by 20 | Viewed by 3617

Abstract

Ecklonia cava (E. cava) can alleviate diet-induced obesity in animal models, and phlorotannins contained in E. cava help prevent hypertrophy-induced adipocyte differentiation. Receptor for advanced glycation end-products (RAGE) is well known to induce hypertrophy of visceral fat and to trigger inflammation [...] Read more.

Ecklonia cava (E. cava) can alleviate diet-induced obesity in animal models, and phlorotannins contained in E. cava help prevent hypertrophy-induced adipocyte differentiation. Receptor for advanced glycation end-products (RAGE) is well known to induce hypertrophy of visceral fat and to trigger inflammation substantially. While the relationship between RAGE and obesity and inflammation has been well-characterized, few studies describe the effects of phlorotannin on RAGE. In this study, we investigated the anti-obesity effects of pyrogallol-phloroglucinol-6,6-bieckol (PPB)—a single compound from the ethanoic extract of E. cava—mediated by a reduction in the inflammation caused by RAGE and RAGE ligands. In visceral fat, PPB (i) significantly inhibited RAGE ligands, (ii) reduced the expression of RAGE, and (iii) reduced the binding ratio between RAGE and RAGE ligands. Under lower expression of RAGE, RAGE ligands and their cognate binding, the differentiation of macrophages found in visceral fat into M1-type—the pro-inflammatory form of this immune cell—was reduced. As the M1-type macrophage decreased, pro-inflammatory cytokines, which cause obesity, decreased in visceral fat. The results of this study highlight the anti-obesity effects of PPB, with the effects mediated by reductions in RAGE, RAGE ligands, and inflammation. Full article

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13 pages, 2030 KiB

Open AccessArticle

Phlorotannins from Ecklonia cava Attenuates Palmitate-Induced Endoplasmic Reticulum Stress and Leptin Resistance in Hypothalamic Neurons

by Seyeon Oh, Myeongjoo Son, Junwon Choi, Chang Hu Choi, Kook Yang Park, Kuk Hui Son and Kyunghee Byun

Mar. Drugs 2019, 17(10), 570; https://doi.org/10.3390/md17100570 - 9 Oct 2019

Cited by 23 | Viewed by 3789

Abstract

Leptin resistance in the hypothalamus has an essential role in obesity. Saturated fatty acids such as palmitate bind to Toll-like receptor 4 (TLR4) and lead to endoplasmic reticulum (ER) stress and leptin resistance. In this study, we evaluated whether extracts of Ecklonia cava [...] Read more.

Leptin resistance in the hypothalamus has an essential role in obesity. Saturated fatty acids such as palmitate bind to Toll-like receptor 4 (TLR4) and lead to endoplasmic reticulum (ER) stress and leptin resistance. In this study, we evaluated whether extracts of Ecklonia cava would attenuate the ER stress induced by palmitate and reduce leptin resistance in hypothalamic neurons and microglia. We added palmitate to these cells to mimic the environment induced by high-fat diet in the hypothalamus and evaluated which of the E. cava phlorotannins—dieckol (DK), 2,7-phloroglucinol-6,6-bieckol (PHB), pyrogallol-phloroglucinol-6,6-bieckol (PPB), or phlorofucofuroeckol-A (PFFA)—had the most potent effect on attenuating leptin resistance. TLR4 and NF-κB expression induced by palmitate was attenuated most effectively by PPB in both hypothalamic neurons and microglia. ER stress markers were increased by palmitate and were attenuated by PPB in both hypothalamic neurons and microglia. Leptin resistance, which was evaluated as an increase in SOCS3 and a decrease in STAT3 with leptin receptor expression, was increased by palmitate and was decreased by PPB in hypothalamic neurons. The culture medium from palmitate-treated microglia increased leptin resistance in hypothalamic neurons and this resistance was attenuated by PPB. In conclusion, PPB attenuated leptin resistance by decreasing ER stress in both hypothalamic neurons and microglia. Full article

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11 pages, 1575 KiB

Open AccessArticle

Omega-3 Fatty Acids-Enriched Fish Oil Activates AMPK/PGC-1α Signaling and Prevents Obesity-Related Skeletal Muscle Wasting

by Shing-Hwa Liu, Chen-Yuan Chiu, Lou-Pin Wang and Meng-Tsan Chiang

Mar. Drugs 2019, 17(6), 380; https://doi.org/10.3390/md17060380 - 25 Jun 2019

Cited by 39 | Viewed by 6609

Abstract

Obesity is known to cause skeletal muscle wasting. This study investigated the effect and the possible mechanism of fish oil on skeletal muscle wasting in an obese rat model. High-fat (HF) diets were applied to induce the defects of lipid metabolism in male [...] Read more.

Obesity is known to cause skeletal muscle wasting. This study investigated the effect and the possible mechanism of fish oil on skeletal muscle wasting in an obese rat model. High-fat (HF) diets were applied to induce the defects of lipid metabolism in male Sprague-Dawley rats with or without substitution of omega-3 fatty acids-enriched fish oil (FO, 5%) for eight weeks. Diets supplemented with 5% FO showed a significant decrease in the final body weight compared to HF diet-fed rats. The decreased soleus muscle weights in HF diet-fed rats could be improved by FO substitution. The decreased myosin heavy chain (a muscle thick filament protein) and increased FOXO3A and Atrogin-1 (muscle atrophy-related proteins) protein expressions in soleus muscles of HF diet-fed rats could also be reversed by FO substitution. FO substitution could also significantly activate adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation, peroxisome-proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α), and PPARγ protein expression and lipoprotein lipase (LPL) mRNA expression in soleus muscles of HF diet-fed rats. These results suggest that substitution of FO exerts a beneficial improvement in the imbalance of lipid and muscle metabolisms in obesity. AMPK/PGC-1α signaling may play an important role in FO-prevented obesity-induced muscle wasting. Full article

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9 pages, 3270 KiB

Open AccessFeature PaperArticle

An Algal Metabolite-Based PPAR-γ Agonist Displayed Anti-Inflammatory Effect via Inhibition of the NF-κB Pathway

by Zhiran Ju, Mingzhi Su, Dandan Li, Jongki Hong, Dong-Soon Im, Suhkmann Kim, Eun La Kim and Jee H. Jung

Mar. Drugs 2019, 17(6), 321; https://doi.org/10.3390/md17060321 - 30 May 2019

Cited by 13 | Viewed by 4568

Abstract

In our previous study, a synthetic compound, (+)-(R,E)-6a1, that incorporated the key structures of anti-inflammatory algal metabolites and the endogenous peroxisome proliferator-activated receptor γ (PPAR-γ) ligand 15-deoxy-∆^12,14-prostaglandin J₂ (15d-PGJ₂), exerted significant PPAR-γ [...] Read more.

In our previous study, a synthetic compound, (+)-(R,E)-6a1, that incorporated the key structures of anti-inflammatory algal metabolites and the endogenous peroxisome proliferator-activated receptor γ (PPAR-γ) ligand 15-deoxy-∆^12,14-prostaglandin J₂ (15d-PGJ₂), exerted significant PPAR-γ transcriptional activity. Because PPAR-γ expressed in macrophages has been postulated as a negative regulator of inflammation, this study was designed to investigate the anti-inflammatory effect of the PPAR-γ agonist, (+)-(R,E)-6a1. Compound (+)-(R,E)-6a1 displayed in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages. Compound (+)-(R,E)-6a1 suppressed the expression of proinflammatory factors, such as nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), possibly by the inhibition of the nuclear factor-κB (NF-κB) pathway. In macrophages, (+)-(R,E)-6a1 suppressed LPS-induced phosphorylation of NF-κB, inhibitor of NF-κB α (IκBα), and IκB kinase (IKK). These results indicated that PPAR-γ agonist, (+)-(R,E)-6a1, exerts anti-inflammatory activity via inhibition of the NF-κB pathway. Full article

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15 pages, 2514 KiB

Open AccessArticle

CYC27 Synthetic Derivative of Bromophenol from Red Alga Rhodomela confervoides: Anti-Diabetic Effects of Sensitizing Insulin Signaling Pathways and Modulating RNA Splicing-Associated RBPs

by Jiao Luo, Bo Jiang, Chao Li, Xiaoling Jia and Dayong Shi

Mar. Drugs 2019, 17(1), 49; https://doi.org/10.3390/md17010049 - 11 Jan 2019

Cited by 10 | Viewed by 4195

Abstract

RNA-binding proteins (RBPs) lie at the center of posttranscriptional regulation and the dysregulation of RBPs contributes to diabetes. Therefore, the modulation of RBPs is anticipated to become a potential therapeutic approach to diabetes. CYC27 is a synthetic derivative of marine bromophenol BDB, which [...] Read more.

RNA-binding proteins (RBPs) lie at the center of posttranscriptional regulation and the dysregulation of RBPs contributes to diabetes. Therefore, the modulation of RBPs is anticipated to become a potential therapeutic approach to diabetes. CYC27 is a synthetic derivative of marine bromophenol BDB, which is isolated from red alga Rhodomela confervoides. In this study, we found that CYC27 significantly lowered the blood glucose levels of diabetic BKS db mice. Moreover, CYC27 effectively ameliorated dyslipidemia in BKS db mice by reducing their total serum cholesterol (TC) and triglyceride (TG) levels. Furthermore, CYC27 was an insulin-sensitizing agent with increased insulin-stimulated phosphorylation of insulin receptors and relevant downstream factors. Finally, to systemically study the mechanisms of CYC27, label-free quantitative phosphoproteomic analysis was performed to investigate global changes in phosphorylation. Enriched GO annotation showed that most regulated phosphoproteins were related to RNA splicing and RNA processing. Enriched KEGG analysis showed that a spliceosome-associated pathway was the predominant pathway after CYC27 treatment. Protein-protein interaction (PPI) analysis showed that CYC27 modulated the process of mRNA splicing via phosphorylation of the relevant RBPs, including upregulated Cstf3 and Srrt. Our results suggested that CYC27 treatment exerted promising anti-diabetic effects by sensitizing the insulin signaling pathways and modulating RNA splicing-associated RBPs. Full article

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2018

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14 pages, 3366 KiB

Open AccessArticle

Effect of Marine Microalga Chlorella pyrenoidosa Ethanol Extract on Lipid Metabolism and Gut Microbiota Composition in High-Fat Diet-Fed Rats

by Xuzhi Wan, Tiantian Li, Dan Liu, Yihan Chen, Yuanyuan Liu, Bin Liu, Huiying Zhang and Chao Zhao

Mar. Drugs 2018, 16(12), 498; https://doi.org/10.3390/md16120498 - 9 Dec 2018

Cited by 54 | Viewed by 5900

Abstract

Effects of marine microalga Chlorella pyrenoidosa 55% ethanol extract (CPE55) on lipid metabolism, gut microbiota and regulation mechanism in high fat diet-fed induced hyperlipidaemia rats were investigated. Structure characterizations of major compounds in CPE55 were determined by ultra-performance liquid chromatography-quadrupole/time of flight mass [...] Read more.

Effects of marine microalga Chlorella pyrenoidosa 55% ethanol extract (CPE55) on lipid metabolism, gut microbiota and regulation mechanism in high fat diet-fed induced hyperlipidaemia rats were investigated. Structure characterizations of major compounds in CPE55 were determined by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The compositions of gut microbiota in rats were analyzed by high-throughput next-generation 16S rRNA gene sequencing. Oral administration with CPE55 markedly alleviated dyslipidemia through improving adverse blood lipid profile and inhibiting hepatic lipid accumulation and steatosis. CPE55 has downregulated the gene expression levels of acetyl CoA carboxylase, sterol regulatory element-binding transcription factor-1c, and 3-hydroxy-3-methyl glutaryl coenzyme A reductase and upregulated adenosine 5′-monophosphate-activated protein kinase-α. It has also improved the abundance of bacteria Alistipes, Prevotella, Alloprevotella, and Ruminococcus1 and decreased the abundances of Turicibacter and Lachnospira. Turicibacter and Lachnospira were both positive correlations of metabolic phenotypes. The findings above illustrated that CPE55 might be developed as food ingredients to ameliorate lipid metabolic disorders and hyperlipidaemia. Full article

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11 pages, 3608 KiB

Open AccessArticle

Effect of Omega-3 Fatty Acid on STAMP2 Expression in the Heart and Kidney of 5/6 Nephrectomy Rat Model

by Hye Won Lee, Su Mi Lee, Mi Hwa Lee, Young Ki Son, Seong Eun Kim and Won Suk An

Mar. Drugs 2018, 16(11), 398; https://doi.org/10.3390/md16110398 - 23 Oct 2018

Cited by 9 | Viewed by 3651

Abstract

Six transmembrane protein of prostate 2 (STAMP2) is a critical modulator of inflammation and metabolism in adipose tissue. There are no data on the expression of STAMP2 in chronic kidney disease, which is an inflammatory disease related to metabolic disorders. This study aimed [...] Read more.

Six transmembrane protein of prostate 2 (STAMP2) is a critical modulator of inflammation and metabolism in adipose tissue. There are no data on the expression of STAMP2 in chronic kidney disease, which is an inflammatory disease related to metabolic disorders. This study aimed to investigate STAMP2 expression in the kidney and heart in 5/6 nephrectomy (Nx) rats, and the effect of omega-3 fatty acid (FA) on STAMP2 expression. Male Sprague Dawley rats were divided into three groups: sham control (0.9% saline), 5/6 Nx (0.9% saline), and 5/6 Nx treated with omega-3 FA (300 mg per kg per day by gastric gavage). The expression of STAMP2 in the kidney and heart were examined by western blotting. Serum creatinine levels were higher in 5/6 Nx rats than in controls. Compared with sham controls, the expression of IκB, NF-κB, NOX4, SREBP-1, and LXR were upregulated and STAMP2 and phosphorylated-AMPK expression were downregulated in the kidney and heart of 5/6 Nx rats. Omega-3 FA supplementation prevented these changes in biomarkers related to inflammation and metabolic lipid disorders. Omega 3-FA supplementation induced the upregulation of STAMP2 protein in 5/6 Nx rats, which was associated with an attenuation of inflammation- and metabolic disease-related markers. Full article

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13 pages, 1816 KiB

Open AccessArticle

Effect of Arthrospira (Spirulina) maxima Supplementation and a Systematic Physical Exercise Program on the Body Composition and Cardiorespiratory Fitness of Overweight or Obese Subjects: A Double-Blind, Randomized, and Crossover Controlled Trial

by Marco Antonio Hernández-Lepe, José Alberto López-Díaz, Marco Antonio Juárez-Oropeza, Rosa Patricia Hernández-Torres, Abraham Wall-Medrano and Arnulfo Ramos-Jiménez

Mar. Drugs 2018, 16(10), 364; https://doi.org/10.3390/md16100364 - 1 Oct 2018

Cited by 25 | Viewed by 7862

Abstract

Excess weight and obesity are major risk factors for many chronic diseases, and weight-loss interventions often include systematic exercise and nutritional supplements. The purpose of this study was to determine the independent/synergistic effects of Arthrospira (Spirulina) maxima supplementation (six weeks, 4.5 g·day⁻¹ [...] Read more.

Excess weight and obesity are major risk factors for many chronic diseases, and weight-loss interventions often include systematic exercise and nutritional supplements. The purpose of this study was to determine the independent/synergistic effects of Arthrospira (Spirulina) maxima supplementation (six weeks, 4.5 g·day⁻¹) and a systematic physical exercise program (six weeks, twice weekly) on the body composition and cardiorespiratory fitness of overweight and obese subjects. To achieve this, 27 overweight and 25 obese sedentary male subjects were assigned to four interventions through a randomized double-blind, crossover controlled trial: A physical exercise program, with (SE) or without (Ex) Spirulina maxima; or no-exercise program, with (Sm) and without (C) Spirulina maxima. The body composition and cardiorespiratory fitness parameters were taken during a maximum intensity test. As compared to the C group, the body fat percentage of the SE, Sm and Ex groups was reduced (p < 0.05), while their maximal oxygen uptake improved (r = −0.40), and obese subjects benefited more significantly. Weight loss, the time to reach fatigue and the onset of blood lactate accumulation were improved in both of the Spirulina maxima supplemented groups, regardless of the subjects’ body weight. Spirulina maxima supplementation synergistically improves the effects of systematic exercise on body composition and cardiorespiratory fitness parameters in overweight, but mostly in individuals with obesity. Trial registration: Clinical Trials, NCT02837666. Registered 19 July 2016. Full article

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15 pages, 819 KiB

Open AccessArticle

Daily Intake of Protein from Cod Residual Material Lowers Serum Concentrations of Nonesterified Fatty Acids in Overweight Healthy Adults: A Randomized Double-Blind Pilot Study

by Iselin Vildmyren, Huy John Vu Cao, Lina Bowitz Haug, Ida Ulrikke Valand, Øyvin Eng, Åge Oterhals, Maren Hoff Austgulen, Alfred Halstensen, Gunnar Mellgren and Oddrun A. Gudbrandsen

Mar. Drugs 2018, 16(6), 197; https://doi.org/10.3390/md16060197 - 5 Jun 2018

Cited by 19 | Viewed by 4513

Abstract

Improved process technologies have allowed fishing vessels to utilize residuals from cod fillet production (head, backbone, skin, cuttings, and entrails) and convert this to high-quality protein powders for human consumption. In this double-blind pilot study, 42 healthy overweight or obese adults were randomized [...] Read more.

Improved process technologies have allowed fishing vessels to utilize residuals from cod fillet production (head, backbone, skin, cuttings, and entrails) and convert this to high-quality protein powders for human consumption. In this double-blind pilot study, 42 healthy overweight or obese adults were randomized to three experimental groups consuming tablets corresponding to 6 g/day of proteins from cod residuals as presscake meal (Cod-PC), presscake and stickwater meal (Cod-PCW), or placebo tablets (control) for eight weeks. The primary outcome of this study was changes in metabolites related to glucose regulation in overweight or obese healthy adults after intake of proteins from cod residuals. Cod-PC supplementation decreased postprandial serum nonesterified fatty acids (NEFA) concentration and increased gene expressions of diglyceride acyltransferase 1 and 2 in subcutaneous adipose tissue compared with controls. Fasting insulin increased while fasting NEFA and 120-min postprandial glucose decreased within the Cod-PC group, but these changes did not differ from the other groups. In conclusion, supplementation with Cod-PC beneficially affected postprandial serum NEFA concentration compared with the other groups in overweight or obese adults. Supplementation with Cod-PCW, which contains a higher fraction of water-soluble protein compared to Cod-PC, did not affect serum markers of glucose regulation. Full article

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12 pages, 673 KiB

Open AccessArticle

Water-Soluble Fish Protein Intake Led to Lower Serum and Liver Cholesterol Concentrations in Obese Zucker fa/fa Rats

by Aslaug Drotningsvik, Linn Anja Vikøren, Svein Are Mjøs, Åge Oterhals, Daniela Pampanin, Ola Flesland and Oddrun Anita Gudbrandsen

Mar. Drugs 2018, 16(5), 149; https://doi.org/10.3390/md16050149 - 1 May 2018

Cited by 18 | Viewed by 5140

Abstract

Proteins from different fish species and different raw materials such as fish fillets and by-products have shown promising cardioprotective effects in rodents and humans, including effects on cholesterol metabolism. Blue whiting is used mainly to produce fish meal for the feed industry and [...] Read more.

Proteins from different fish species and different raw materials such as fish fillets and by-products have shown promising cardioprotective effects in rodents and humans, including effects on cholesterol metabolism. Blue whiting is used mainly to produce fish meal for the feed industry and during this production, a water-soluble protein fraction, containing small peptides that are easily absorbed and may hold bioactive properties, is isolated. The effects of water-soluble fish protein on cholesterol metabolism were investigated in twelve male obese Zucker fa/fa rats. Rats were fed diets with water-soluble protein from blue whiting (BWW) as 1/3 of the total protein and the remaining 2/3 as casein (BWW group) or with casein as the sole protein source (control group). After 5 weeks intervention, the BWW group had lower serum total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol concentrations and lower cholesteryl ester concentration compared to controls. Hepatic concentrations of cholesterol, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and LDL receptors were also lower in the BWW group. The groups had a similar concentration of serum total bile acids and similar fecal excretions of cholesterol and bile acids. To conclude, the BWW diet led to lower concentrations of serum and liver cholesterol in obese Zucker fa/fa rats, probably due to lower hepatic cholesterol synthesis. Full article

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12 pages, 303 KiB

Open AccessReview

Marine Omega-3 Fatty Acids, Complications of Pregnancy and Maternal Risk Factors for Offspring Cardio-Metabolic Disease

by Melinda Phang and Michael R. Skilton

Mar. Drugs 2018, 16(5), 138; https://doi.org/10.3390/md16050138 - 24 Apr 2018

Cited by 11 | Viewed by 5305

Abstract

Marine omega-3 polyunsaturated fatty acids (n-3 PUFA) are important nutrients during periods of rapid growth and development in utero and infancy. Maternal health and risk factors play a crucial role in birth outcomes and subsequently offspring cardio-metabolic health. Evidence from observational studies and [...] Read more.

Marine omega-3 polyunsaturated fatty acids (n-3 PUFA) are important nutrients during periods of rapid growth and development in utero and infancy. Maternal health and risk factors play a crucial role in birth outcomes and subsequently offspring cardio-metabolic health. Evidence from observational studies and randomized trials have suggested a potential association of maternal intake of marine n-3 PUFAs during pregnancy with pregnancy and birth outcomes. However, there is inconsistency in the literature on whether marine n-3 PUFA supplementation during pregnancy can prevent maternal complications of pregnancy. This narrative literature review summarizes recent evidence on observational and clinical trials of marine n-3 PUFA intake on maternal risk factors and effects on offspring cardio-metabolic health. The current evidence generally does not support a role of maternal n-3 PUFA supplementation in altering the incidence of gestational diabetes, pregnancy-induced hypertension, or pre-eclampsia. It may be that benefits from marine n-3 PUFA supplementation are more pronounced in high-risk populations, such as women with a history of complications of pregnancy, or women with low marine n-3 PUFA intake. Discrepancies between studies may be related to differences in study design, dosage, fatty acid interplay, and length of treatment. Further prospective double-blind studies are needed to clarify the impact of long-chain marine n-3 PUFAs on risk factors for cardio-metabolic disease in the offspring. Full article

17 pages, 4415 KiB

Open AccessArticle

Chitin Oligosaccharide Modulates Gut Microbiota and Attenuates High-Fat-Diet-Induced Metabolic Syndrome in Mice

by Junping Zheng, Gong Cheng, Qiongyu Li, Siming Jiao, Cui Feng, Xiaoming Zhao, Heng Yin, Yuguang Du and Hongtao Liu

Mar. Drugs 2018, 16(2), 66; https://doi.org/10.3390/md16020066 - 19 Feb 2018

Cited by 76 | Viewed by 8310

Abstract

Gut microbiota has been proved to be an indispensable link between nutrient excess and metabolic syndrome, and chitin oligosaccharide (NACOS) has displayed therapeutic effects on multiple diseases such as cancer and gastritis. In this study, we aim to confirm whether NACOS can ameliorate [...] Read more.

Gut microbiota has been proved to be an indispensable link between nutrient excess and metabolic syndrome, and chitin oligosaccharide (NACOS) has displayed therapeutic effects on multiple diseases such as cancer and gastritis. In this study, we aim to confirm whether NACOS can ameliorate high-fat diet (HFD)-induced metabolic syndrome by rebuilding the structure of the gut microbiota community. Male C57BL/6J mice fed with HFD were treated with NACOS (1 mg/mL) in drinking water for five months. The results indicate that NACOS improved glucose metabolic disorder in HFD-fed mice and suppressed mRNA expression of the protein regulators related to lipogenesis, gluconeogenesis, adipocyte differentiation, and inflammation in adipose tissues. Additionally, NACOS inhibited the destruction of the gut barrier in HFD-treated mice. Furthermore, 16S ribosome RNA sequencing of fecal samples demonstrates that NACOS promoted the growth of beneficial intestinal bacteria remarkably and decreased the abundance of inflammogenic taxa. In summary, NACOS partly rebuilt the microbial community and improved the metabolic syndrome of HFD-fed mice. These data confirm the preventive effects of NACOS on nutrient excess-related metabolic diseases. Full article

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13 pages, 1681 KiB

Open AccessArticle

Combination Treatment of Deep Sea Water and Fucoidan Attenuates High Glucose-Induced Insulin-Resistance in HepG2 Hepatocytes

by Shan He, Wei-Bing Peng and Hong-Lei Zhou

Mar. Drugs 2018, 16(2), 48; https://doi.org/10.3390/md16020048 - 2 Feb 2018

Cited by 14 | Viewed by 5862

Abstract

Insulin resistance (IR) plays a central role in the development of several metabolic diseases, which leads to increased morbidity and mortality rates, in addition to soaring health-care costs. Deep sea water (DSW) and fucoidans (FPS) have drawn much attention in recent years because [...] Read more.

Insulin resistance (IR) plays a central role in the development of several metabolic diseases, which leads to increased morbidity and mortality rates, in addition to soaring health-care costs. Deep sea water (DSW) and fucoidans (FPS) have drawn much attention in recent years because of their potential medical and pharmaceutical applications. This study investigated the effects and mechanisms of combination treatment of DSW and FPS in improving IR in HepG2 hepatocytes induced by a high glucose concentration. The results elucidated that co-treatment with DSW and FPS could synergistically repress hepatic glucose production and increase the glycogen level in IR-HepG2 cells. In addition, they stimulated the phosphorylation levels of the components of the insulin signaling pathway, including tyrosine phosphorylation of IRS-1, and serine phosphorylation of Akt and GSK-3β. Furthermore, they increased the phosphorylation of AMPK and ACC, which in turn decreased the intracellular triglyceride level. Taken together, these results suggested that co-treatment with DSW and FPS had a greater improving effect than DSW or FPS alone on IR. They might attenuate IR by targeting Akt/GSK-3β and AMPK pathways. These results may have some implications in the treatment of metabolic diseases. Full article

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16 pages, 7185 KiB

Open AccessArticle

Protective Effect of Meretrix meretrix Oligopeptides on High-Fat-Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

by Fangfang Huang, Jiajia Wang, Fangmiao Yu, Yunping Tang, Guofang Ding, Zuisu Yang and Yu Sun

Mar. Drugs 2018, 16(2), 39; https://doi.org/10.3390/md16020039 - 23 Jan 2018

Cited by 37 | Viewed by 5896

Abstract

The present study investigated the effects of MMO (Meretrix meretrix oligopeptides) on mice fed a high-fat diet. Mice were fed either a normal control diet (NC) or a high-fat diet (HFD) without or with MMO (50 mg/kg or 250 mg/kg) for four [...] Read more.

The present study investigated the effects of MMO (Meretrix meretrix oligopeptides) on mice fed a high-fat diet. Mice were fed either a normal control diet (NC) or a high-fat diet (HFD) without or with MMO (50 mg/kg or 250 mg/kg) for four weeks. Levels of ALT, AST, liver tissue GSH-Px, and SOD activities, MDA levels were measured using commercially available kits; HE staining was performed to analyze pathologic changes of the liver; a TEM assay was performed to measure the ultrastructural alterations of the mitochondria, and Western blotting was performed to detect the expression of gene proteins related to lipid metabolism, inflammation, and liver apoptosis. After six weeks, body weight, ALT, AST, and MDA levels were significantly increased, and GSH-Px levels and SOD activities were significantly decreased in the HFD control group compared with the NC group. Consumption of the HFD compared with the NC caused fatty liver abnormal mitochondria with loss of cristae, intramitochondrial granules, and a swollen and rarefied matrix. Administration of MMO significantly decreased body weight gain, and ALT, AST, and MDA levels; increased SOD activity and GSH-Px levels; alleviated fatty liver steatosis; decreased the early apoptosis population; downregulated SREBP-1c, Bax, Caspase-9, Caspase-3, TNF-α, and NF-κB protein levels; and upregulated PPAR-α, Bcl-2, and AMPK-α, compared with the HFD control group. MMO exhibited protective effects in mice with NAFLD by regulating the NF-κB anti-inflammation signaling pathways to inhibit inflammation, regulate AMPK-α, PPAR-α and SREBP-1c to improve lipid metabolism disorder, and regulate Bcl-2/Bax anti-apoptosis signaling pathways to prevent liver cell apoptosis. These results suggest that dietary supplementation with MMO ameliorates high-fat-diet-induced NAFLD. Full article

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13 pages, 2207 KiB

Open AccessArticle

Lipid-Lowering Polyketides from the Fungus Penicillium Steckii HDN13-279

by Guihong Yu, Shuai Wang, Lu Wang, Qian Che, Tianjiao Zhu, Guojian Zhang, Qianqun Gu, Peng Guo and Dehai Li

Mar. Drugs 2018, 16(1), 25; https://doi.org/10.3390/md16010025 - 12 Jan 2018

Cited by 21 | Viewed by 4926

Abstract

Seven new polyketides, named tanzawaic acids R–X (1–6, 11), along with seven known analogues (7–10 and 12–14), were isolated from Penicillium steckii HDN13-279. Their structures, including the absolute configurations, were elucidated by [...] Read more.

Seven new polyketides, named tanzawaic acids R–X (1–6, 11), along with seven known analogues (7–10 and 12–14), were isolated from Penicillium steckii HDN13-279. Their structures, including the absolute configurations, were elucidated by NMR, MS, X-ray diffraction, circular dichroism (CD) analyses and chemical derivatization. Five compounds (2, 3, 6, 10 and 12) significantly decreased the oleic acid (OA)-elicited lipid accumulation in HepG2 liver cells at the concentration of 10 μM, among which, four compounds (3, 6, 10 and 12) significantly decreased intracellular total cholesterol (TC) levels and three Compounds (3, 6, and 10) significantly decreased intracellular triglyceride (TG) levels. Moreover, the TG-lowering capacities of compounds 6 and 10 were comparable with those of simvastatin, with the TG levels being nearly equal to blank control. This is the first report on the lipid-lowering activity of tanzawaic acid derivatives. Full article

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2017

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3022 KiB

Open AccessArticle

Deep Sea Water Improves Abnormalities in Lipid Metabolism through Lipolysis and Fatty Acid Oxidation in High-Fat Diet-Induced Obese Rats

by Wei-Tang Chang, Tsung-Yueh Lu, Ming-Ching Cheng, Hsun-Chi Lu, Mei-Fang Wu and Chin-Lin Hsu

Mar. Drugs 2017, 15(12), 386; https://doi.org/10.3390/md15120386 - 11 Dec 2017

Cited by 12 | Viewed by 5169

Abstract

Deep sea water (DSW) is a natural marine resource that has been utilized for food, agriculture, cosmetics, and medicine. The aim of this study was to investigate whether DSW has beneficial lipid metabolic effects in an animal model. Our previous in vitro study [...] Read more.

Deep sea water (DSW) is a natural marine resource that has been utilized for food, agriculture, cosmetics, and medicine. The aim of this study was to investigate whether DSW has beneficial lipid metabolic effects in an animal model. Our previous in vitro study indicated that DSW significantly decreased the intracellular triglyceride and glycerol-3-phosphate dehydrogenase activity in 3T3-L1 adipocytes. DSW also inhibited the gene levels of adipocyte differentiation, lipogenesis, and adipocytokines, and up-regulated gene levels of lipolysis and fatty acid oxidation. In the present study, the results showed that body weight, liver, adipose tissue, hepatic triglycerides and cholesterol, and serum parameters in the high-fat diet (HFD) + DSW groups were significantly lower compared to the HFD group. Moreover, the fecal output of total lipids, triglycerides, and cholesterol in the HFD + DSW groups was significantly higher than that of the HFD group. Regarding gene expression, DSW significantly increased the gene levels of lipolysis and fatty acid oxidation, and decreased the gene levels of adipocytokine in the adipose tissue of rats with HFD-induced obesity. These results indicate a potential molecular mechanism by which DSW can suppress obesity in rats with HFD-induced obesity through lipolysis and fatty acid oxidation. Full article

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