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1.
Int J Mol Sci ; 25(8)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38674060

ABSTRACT

Mandarin peel, a main by-product from the processing of citrus juice, has been highlighted for its various bioactivities and functional ingredients. Our previous study proved the inhibitory effects of Celluclast extract from mandarin peel (MPCE) on lipid accumulation and differentiation in 3T3-L1 adipocytes. Therefore, the current study aimed to evaluate the anti-obesity effect of MPCE in high-fat diet (HFD)-induced obese mice. The high-performance liquid chromatography (HPLC) analysis exhibited that narirutin and hesperidin are the main active components of MPCE. Our current results showed that MPCE supplementation decreased adiposity by reducing body and organ weights in HFD-induced obese mice. MPCE also reduced triglyceride (TG), alanine transaminase (ALT), aspartate transaminase (AST), and leptin contents in the serum of HFD-fed mice. Moreover, MPCE significantly inhibited hepatic lipid accumulation by regulating the expression levels of proteins associated with lipid metabolism, including sterol regulatory element-binding protein (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Furthermore, MPCE administration significantly inhibited both adipogenesis and lipogenesis, with modulation of energy metabolism by activating 5' adenosine monophosphate-activated protein kinase (AMPK) and lipolytic enzymes such as hormone-sensitive lipase (HSL) in the white adipose tissue (WAT). Altogether, our findings indicate that MPCE improves HFD-induced obesity and can be used as a curative agent in pharmaceuticals and nutraceuticals to alleviate obesity and related disorders.


Subject(s)
Adipogenesis , Citrus , Diet, High-Fat , Disaccharides , Energy Metabolism , Flavanones , Mice, Inbred C57BL , Obesity , Plant Extracts , Animals , Diet, High-Fat/adverse effects , Obesity/metabolism , Obesity/drug therapy , Obesity/etiology , Citrus/chemistry , Mice , Energy Metabolism/drug effects , Plant Extracts/pharmacology , Male , Adipogenesis/drug effects , Lipid Metabolism/drug effects , 3T3-L1 Cells , Anti-Obesity Agents/pharmacology , Liver/metabolism , Liver/drug effects , Lipogenesis/drug effects , Triglycerides/metabolism , Triglycerides/blood
2.
Mar Drugs ; 22(3)2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38535450

ABSTRACT

A biocompatible, heterogeneous, fucose-rich, sulfated polysaccharide (fucoidan) is biosynthesized in brown seaweed. In this study, fucoidan was isolated from Padina arborescens (PAC) using celluclast-assisted extraction, purified, and evaluated for its anti-inflammatory potential in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Structural analyses were performed using Fourier transform infrared (FTIR) and scanning electron microscopy. Among the purified fucoidans, fucoidan fraction 5 (F5) exhibited strong inhibitory activity against LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine generation through the regulation of iNOS/COX-2, MAPK, and NF-κB signaling in LPS-induced RAW 264.7 cells. Determination of the structural characteristics indicated that purified F5 exhibited characteristics similar to those of commercial fucoidan. In addition, further analyses suggested that F5 inhibits LPS-induced toxicity, cell death, and NO generation in zebrafish models. Taken together, these findings imply that P. arborescens fucoidans have exceptional anti-inflammatory action, both in vitro and in vivo, and that they may have prospective uses in the functional food sector.


Subject(s)
Lipopolysaccharides , Phaeophyceae , Animals , Zebrafish , Polysaccharides , Inflammation , Nitric Oxide
3.
Mar Drugs ; 21(8)2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37623739

ABSTRACT

The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, Gigantidas vrijenhoeki. The G. vrijenhoeki protein was hydrolyzed by various hydrolytic enzymes. The peptic hydrolysate exhibited the highest ACE-inhibitory activity and was fractionated into four molecular weight ranges by ultrafiltration. The <1 kDa fraction exhibited the highest ACE inhibitory activity and was found to have 11 peptide sequences. Among the analyzed peptides, KLLWNGKM exhibited stronger ACE inhibitory activity and an IC50 value of 0.007 µM. To investigate the ACE-inhibitory activity of the analyzed peptides, a molecular docking study was performed. KLLWNGKM exhibited the highest binding energy (-1317.01 kcal/mol), which was mainly attributed to the formation of hydrogen bonds with the ACE active pockets, zinc-binding motif, and zinc ion. These results indicate that G. vrijenhoeki-derived peptides can serve as nutritional and pharmacological candidates for controlling blood pressure.


Subject(s)
Mytilidae , Peptidyl-Dipeptidase A , Animals , Molecular Docking Simulation , Peptides/pharmacology , Zinc
4.
Mar Drugs ; 21(7)2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37504900

ABSTRACT

Microalgae are proposed to have powerful applications for human health in the pharmaceutical and food industries. Tetraselmis species (sp.), which are green microalgae, were identified as a source of broad-spectrum health-promoting biological activities. However, the bioactivity of these species has not been elucidated. We aimed to confirm the antioxidant, antiviral, and anti-inflammatory effects of Tetraselmis sp. extract (TEE). TEE showed 2,2-diphenyl-1-picryl-hydrazyl-hydrate radical and hydrogen peroxide scavenging activities and reduced plaque formation in Vero E6 cells infected with vaccinia virus. TEE treatment also significantly inhibited nitric oxide (NO) production and improved cell viability in lipopolysaccharide (LPS)-induced RAW264.7 cells. These anti-inflammatory effects were further analyzed in LPS-induced RAW 264.7 cells and the zebrafish model. Further, TEE reduced induced NO synthase expression and proinflammatory cytokine release, including tumor necrosis factor-α, interleukin-6, and interleukin-1ß, through MAPKs and NF-κB-dependent mechanisms. Further analysis revealed that TEE increased the survival rate and reduced cell death and NO production in an LPS-stimulated zebrafish model. Further, high-performance liquid chromatography revealed a strong presence of the carotenoid lutein in TEE. Overall, the results suggest that lutein-enriched TEE may be a potent antioxidant, antiviral, and anti-inflammatory agent that could be sustainably utilized in industrial applications.


Subject(s)
Antioxidants , Lutein , Animals , Mice , Humans , Antioxidants/pharmacology , Lutein/pharmacology , Lutein/metabolism , Zebrafish/metabolism , Lipopolysaccharides/pharmacology , Antiviral Agents/pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anti-Inflammatory Agents/pharmacology , NF-kappa B/metabolism , RAW 264.7 Cells , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism
5.
Appl Radiat Isot ; 199: 110881, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37267776

ABSTRACT

Thymus quinquecostatus Celak (TQC) is an aromatic herb, that possesses a wide range of biological properties. In the present study, we investigated the radio-protective effect of TQC water extract (TQCW) in gamma ray-exposed splenocytes, a peripheral immune cell and mice. Our results showed that the treatment with TQCW dose-dependently increased the viability of splenocytes. TQCW significantly increased the proliferation of splenocytes by reducing the production of intracellular reactive oxygen species (ROS) in 2 Gy-exposed splenocytes. Moreover, TQCW enhanced the hemopoietic system as increasing the number of endogenous spleen colony-forming units, and the number and the proliferation of splenocytes in 7 Gy-exposed mice. These results suggest that TQCW protects mice by enhancing the splenocytes proliferation and hemopoietic systems following exposure to gamma rays.


Subject(s)
Biological Products , Thymus Plant , Animals , Mice , Reactive Oxygen Species
6.
Food Chem Toxicol ; 177: 113864, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37263571

ABSTRACT

Recently, a new mechanism has revealed that gut microbiota plays a pivotal role in metabolizing fructose to acetate that facilitates hepatic lipogenesis. Therefore, our study investigated the role of microbiome on abnormal lipid synthesis in the presence of fructose and identified attenuating effects of Ishige okamurae Celluclast extract (IOCE) against fructose-induced fatty liver. The results indicated that oral administration of IOCE (150 and 300 mg/kg/day for 12 weeks) significantly reduced both gut microbiota-mediated and -non-mediated hepatic lipogenesis simultaneously triggered by fructose metabolism. IOCE reduced hepatic triglyceride accumulation and expression levels of key enzymes for glucolipid metabolism. In addition, IOCE regulated fatty acid synthesis, ß-oxidation, and improved hepatic inflammation. Furthermore, IOCE inhibited direct fructose-to-acetate conversion and altered the compositions of gut microbiota. These findings suggest that IOCE might serve as a potential prebiotic dietary supplement by ameliorating fatty liver through dual regulation of classical lipogenic pathway and gut microbiota.


Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Mice , Animals , Lipid Metabolism , Fructose/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Diet , Liver , Acetates/pharmacology , Mice, Inbred C57BL , Diet, High-Fat
7.
Food Sci Anim Resour ; 43(1): 184-194, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36789190

ABSTRACT

Recently, interest in food-derived bioactive peptides as promising ingredients for the prevention and improvement of hypertension is increasing. The purpose of this study was to determine the structure and antihypertensive effect of an antioxidant peptide purified from velvet antler in a previous study and evaluate its potential as a various bioactive peptide. Molecular weight (MW) and amino acid sequences of the purified peptide were determined by quadrupole time-of-flight electrospray ionization mass spectroscopy. The angiotensin I-converting enzyme (ACE) inhibition activity of the purified peptide was assessed by enzyme reaction methods and in silico molecular docking analysis to determine the interaction between the purified peptide and ACE. Also, antihypertensive effect of the purified peptide in spontaneously hypertensive rats (SHRs) was investigated. The purified antioxidant peptide was identified to be a pentapeptide Asp-Asn-Arg-Tyr-Tyr with a MW of 730.31 Da. This pentapeptide showed potent inhibition activity against ACE (IC50 value, 3.72 µM). Molecular docking studies revealed a good and stable binding affinity between purified peptide and ACE and indicated that the purified peptide could interact with HOH2570, ARG522, ARG124, GLU143, HIS387, TRP357, and GLU403 residues of ACE. Furthermore, oral administration of the pentapeptide significantly reduced blood pressure in SHRs. The pentapeptide derived from enzymatic hydrolysate of velvet antler is an excellent ACE inhibitor. It might be effectively applied as an animal-based functional food ingredient.

8.
Fitoterapia ; 163: 105342, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36330897

ABSTRACT

Ishophloroglucin A (IPA) is one of the most abundant and active compounds in Ishige okamurae and is known to be a potential therapeutic candidate for the improvement of metabolic diseases. However, IPA on the inhibitory effects of protein tyrosine phosphatase 1B (PTP1B) and adipogenesis have not been determined. In this study, we investigated the effects of IPA on the inhibition of PTP1B, the effects on adipogenesis, and its mechanisms of action in 3 T3-L1 adipocytes. The IC50 value of IPA against PTP1B was 0.43 µM, which evidenced the higher inhibition activity than that of ursolic acid, a known PTP1B inhibitor. For further insight, we predicted the 3D structure of PTP1B and used a docking algorithm to simulate the binding between PTP1B and IPA. Molecular docking studies revealed a high and stable binding affinity between IPA and PTP1B and indicated that the IPA could interacts with the amino acid residues located in a region to the active site of PTP1B. Further studies showed that IPA concentrations between 6.25 µM and 25 µM dose-dependently attenuated adipogenesis, which was accompanied by a reduction in adipogenesis-related factors, including PPARγ, C/EBPα, SREBP-1c, and FABP4. Our findings suggested that IPA may be a promising natural compound for the treatment of obesity and related diseases.


Subject(s)
Adipogenesis , Phaeophyceae , Mice , Animals , 3T3-L1 Cells , Molecular Docking Simulation , Molecular Structure , Adipocytes , Phaeophyceae/chemistry , Enzyme Inhibitors/pharmacology
9.
Mar Drugs ; 19(10)2021 Oct 13.
Article in English | MEDLINE | ID: mdl-34677466

ABSTRACT

Turbo cornutus, the horned turban sea snail, is found along the intertidal and basaltic shorelines of Jeju Island, Korea. T. cornutus feeds on seaweeds (e.g., Undaria sp., and Ecklonia sp.) composed of diverse antioxidants. This study identified potential antioxidant properties from T. cornutus viscera tissues. Diverse extracts were evaluated for their hydrogen peroxide (H2O2) scavenging activities. T. cornutus viscera protamex-assisted extracts (TVP) were purified by gel filtration chromatography (GFC), and potential antioxidant properties were analyzed for their amino acid sequences and its peroxidase inhibition effects by in silico molecular docking and in vitro analysis. According to the results, T. cornutus viscera tissues are composed of many protein contents with each over 50%. Among the extracts, TVP possessed the highest H2O2 scavenging activity. In addition, TVP-GFC-3 significantly decreased intracellular reactive oxygen species (ROS) levels and increased cell viability in H2O2-treated HepG2 cells without cytotoxicity. TVP-GFC-3 comprises nine low molecular bioactive peptides (ELR, VGPQ, TDY, ALPHA, PAH, VDY, WSDK, VFSP, and FAPQY). Notably, the peptides dock to the active site of the myeloperoxidase (MPO), especially TDY and FAPQY showed the MPO inhibition effects with IC50 values of 646.0 ± 45.0 µM and 57.1 ± 17.7 µM, respectively. Altogether, our findings demonstrated that T. cornutus viscera have potential antioxidant properties that can be used as high value-added ingredients.


Subject(s)
Antioxidants/pharmacology , Free Radical Scavengers/pharmacology , Snails , Animals , Antioxidants/chemistry , Aquatic Organisms , Hep G2 Cells/drug effects , Humans , Hydrogen Peroxide , Molecular Docking Simulation , Viscera/chemistry
10.
Fitoterapia ; 152: 104921, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33984434

ABSTRACT

Accumulating evidence has shown an association between osteoporosis and oxidative damage. In the present study, the protective effects of diphlorethohydroxycarmalol (DPHC) isolated from the brown algae Ishige okamurae against H2O2-induced oxidative damage via bone morphogenetic protein 2 (BMP2)/ runt-related transcription factor 2 (Runx2) signaling were investigated using MC3T3-E1 osteoblastic cells. DPHC counteracted the reduction in cell viability caused by H2O2 exposure and protected against H2O2-induced dysfunction, demonstrated by improved cellular alkaline phosphatase (ALP) activity and calcium deposition. In addition, treatment with 0.05-0.2 mM DPHC elevated the protein expression of osteoblast differentiation factors type 1 collagen, ALP, p-Smad1/5, Osterix, BMP2, and Runx2, in response to H2O2-induced oxidative damage. Importantly, DPHC decreased the expression levels of receptor activator of nuclear factor kappa-B ligand, which promotes bone resorption, and inhibited the H2O2-induced generation of reactive oxygen species. Taken together, the results suggest that DPHC counteracts the effects of oxidative stress in osteoblastic cells and has the potential to be effective in preventing and alleviating osteoporosis.


Subject(s)
Heterocyclic Compounds, 3-Ring/pharmacology , Osteoblasts/drug effects , Oxidative Stress/drug effects , Phaeophyceae/chemistry , Signal Transduction , 3T3 Cells , Animals , Bone Morphogenetic Protein 2 , Cell Differentiation/drug effects , Cell Survival/drug effects , Core Binding Factor Alpha 1 Subunit , Heterocyclic Compounds, 3-Ring/isolation & purification , Hydrogen Peroxide , Mice , Molecular Structure , Reactive Oxygen Species/metabolism , Republic of Korea
11.
Int J Mol Sci ; 22(8)2021 Apr 08.
Article in English | MEDLINE | ID: mdl-33917915

ABSTRACT

Protocatechuic aldehyde (PA) is a naturally occurring phenolic compound that is a potent inhibitor of mushroom tyrosinase. However, the molecular mechanisms of the anti-melanogenesis activity of PA have not yet been reported. The aim of the current study was to clarify the melanogenesis inhibitory effects of PA and its molecular mechanisms in murine melanoma cells (B16F10). We first predicted the 3D structure of tyrosinase and used a molecular docking algorithm to simulate binding between tyrosinase and PA. These molecular modeling studies calculated a binding energy of -527.42 kcal/mol and indicated that PA interacts with Cu400 and 401, Val283, and His263. Furthermore, PA significantly decreased α-MSH-induced intracellular tyrosinase activity and melanin content in a dose-dependent manner. PA also inhibited key melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH-stimulated B16F10 cells. In addition, PA decreased MITF expression levels by inhibiting phosphorylation of cAMP response element-binding protein (CREB) and cAMP-dependent protein kinase A (PKA). These results demonstrate that PA can effectively suppress melanin synthesis in melanoma cells. Taken together, our results show that PA could serve as a potential inhibitor of melanogenesis, and hence could be explored as a possible skin-lightening agent.


Subject(s)
Benzaldehydes/pharmacology , Catechols/pharmacology , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Melanins/biosynthesis , Microphthalmia-Associated Transcription Factor/genetics , alpha-MSH/metabolism , Animals , Benzaldehydes/chemistry , Catechols/chemistry , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP-Dependent Protein Kinases/genetics , Melanoma, Experimental , Mice , Microphthalmia-Associated Transcription Factor/metabolism , Monophenol Monooxygenase/metabolism
12.
Mar Drugs ; 19(2)2021 Feb 04.
Article in English | MEDLINE | ID: mdl-33557339

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 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.


Subject(s)
Adipogenesis/drug effects , Chlorophyll/pharmacology , Lipid Metabolism/drug effects , Seaweed , 3T3-L1 Cells , Animals , CCAAT-Enhancer-Binding Proteins/genetics , Chlorophyll/analogs & derivatives , Chlorophyll/therapeutic use , Chromatography, High Pressure Liquid , Down-Regulation , Fatty Acid-Binding Proteins/genetics , Mice , Obesity/drug therapy , PPAR gamma/genetics , Seaweed/chemistry , Sterol Regulatory Element Binding Protein 1/genetics
13.
Cell Biochem Funct ; 39(4): 546-554, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33474761

ABSTRACT

Diphlorethohydroxycarmalol (DPHC) is a marine polyphenolic compound derived from brown alga Ishige okamurae. A previously study has suggested that DPHC possesses strong mushroom tyrosinase inhibitory activity. However, the anti-melanogenesis effect of DPHC has not been reported at cellular level. The objective of the present study was to clarify the melanogenesis inhibitory effect of DPHC and its molecular mechanisms in murine melanoma cells (B16F10) and zebrafish model. DPHC significantly inhibited tyrosinase activity and melanin content dose-dependently in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. This polyphenolic compound also suppressed the expression of phosphorylation of cAMP response element-binding protein (CREB) by attenuating phosphorylation of cAMP-dependent protein kinase A, resulting in decreased MITF expression levels. Furthermore, DPHC downregulated MITF protein expression levels by promoting the phosphorylation of extracellular signal-regulated kinase. It also inhibited tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH stimulated B16F10 cells. In in vivo studies using zebrafish, DPHC also markedly inhibited melanin synthesis in a dose-dependent manner. These results demonstrate that DPHC can effectively inhibit melanogenesis in melanoma cells in vitro and in zebrafish in vivo, suggesting that DPHC could be applied in fields of pharmaceutical and cosmeceuticals as a skin-whitening agent. Significance of study: The present study showed for the first time that DPHC could inhibit a-MSH-stimulated melanogenesis via PKA/CREB and ERK pathway in melanoma cells. It also could inhibit pigmentation in vivo in a zebrafish model. This evidence suggests that DPHC has potential as a skin whitening agent. Taken together, DPHC could be considered as a novel anti-melanogenic agent to be applied in cosmetic, food, and medical industry.


Subject(s)
Antineoplastic Agents/pharmacology , Down-Regulation/drug effects , Heterocyclic Compounds, 3-Ring/pharmacology , Melanoma/drug therapy , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Cell Survival/drug effects , Cyclic AMP Response Element-Binding Protein/antagonists & inhibitors , Cyclic AMP Response Element-Binding Protein/metabolism , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Cyclic AMP-Dependent Protein Kinases/metabolism , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Extracellular Signal-Regulated MAP Kinases/metabolism , Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/isolation & purification , Melanoma/metabolism , Melanoma/pathology , Mice , Microphthalmia-Associated Transcription Factor/antagonists & inhibitors , Microphthalmia-Associated Transcription Factor/metabolism , Molecular Structure , Phaeophyceae/chemistry , Structure-Activity Relationship , Tumor Cells, Cultured , Zebrafish/embryology , alpha-MSH/antagonists & inhibitors , alpha-MSH/metabolism
14.
Int J Mol Sci ; 21(13)2020 Jun 29.
Article in English | MEDLINE | ID: mdl-32610570

ABSTRACT

Ultraviolet radiation (UV) is a major causative factor of DNA damage, inflammatory responses, reactive oxygen species (ROS) generation and a turnover of various cutaneous lesions resulting in skin photoaging. The purpose of this study is to investigate the protective effect of protocatechuic aldehyde (PA), which is a nature-derived compound, against UVA-induced photoaging by using human dermal fibroblast (HDF) cells. In this study, our results indicated that PA significantly reduced the levels of intracellular ROS, nitric oxide (NO), and prostaglandins-E2 (PGE2) in UVA-irradiated HDF cells. It also inhibited the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Besides, PA significantly suppressed the expression of matrix metalloproteinases-1 (MMP-1) and pro-inflammatory cytokines and promoted collagen synthesis in the UVA-irradiated HDF cells. These events occurred through the regulation of activator protein 1 (AP-1), nuclear factor-κB (NF-κB), and p38 signaling pathways in UVA-irradiated HDF cells. Our findings suggest that PA enhances the protective effect of UVA-irradiated photoaging, which is associated with ROS scavenging, anti-wrinkle, and anti-inflammatory activities. Therefore, PA can be a potential candidate for the provision of a protective effect against UVA-stimulated photoaging in the pharmaceutical and cosmeceutical industries.


Subject(s)
Benzaldehydes/pharmacology , Catechols/pharmacology , Fibroblasts/drug effects , Skin Aging/physiology , Anti-Inflammatory Agents/pharmacology , Benzaldehydes/metabolism , Catechols/metabolism , Cell Line , China , Dinoprostone/metabolism , Fibroblasts/radiation effects , Humans , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Skin/metabolism , Skin/physiopathology , Skin Physiological Phenomena/drug effects , Transcription Factor AP-1/metabolism , Ultraviolet Rays/adverse effects
15.
Mar Drugs ; 17(11)2019 Nov 10.
Article in English | MEDLINE | ID: mdl-31717668

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 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.


Subject(s)
Anti-Obesity Agents/pharmacology , Heterocyclic Compounds, 3-Ring/pharmacology , Obesity/drug therapy , Phaeophyceae/metabolism , Adipose Tissue/drug effects , Administration, Oral , Animals , Anti-Obesity Agents/administration & dosage , Anti-Obesity Agents/isolation & purification , Diet, High-Fat , Disease Models, Animal , Dose-Response Relationship, Drug , Heterocyclic Compounds, 3-Ring/administration & dosage , Heterocyclic Compounds, 3-Ring/isolation & purification , Lipid Metabolism/drug effects , Lipogenesis/drug effects , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/physiopathology , Weight Gain/drug effects
16.
Int J Mol Sci ; 20(20)2019 Oct 19.
Article in English | MEDLINE | ID: mdl-31635129

ABSTRACT

Velvet antler has a long history in traditional medicine. It is also an important healthy ingredient in food as it is rich in protein. However, there has been no report about antioxidant peptides extracted from velvet antler by enzymatic hydrolysis. Thus, the objective of this study was to hydrolyze velvet antler using different commercial proteases (Acalase, Neutrase, trypsin, pepsin, and α-chymotrypsin). Antioxidant activities of different hydrolysates were investigated using peroxyl radical scavenging assay by electron spin resonance spectrometry. Among all enzymatic hydrolysates, Alcalase hydrolysate exhibited the highest peroxyl radical scavenging activity. Alcalase hydrolysate was then purified using ultrafiltration, gel filtration, and reverse-phase high performance liquid chromatography. The purified peptide was identified to be Trp-Asp-Val-Lys (tetrapeptide) with molecular weight of 547.29 Da by Q-TOF ESI mass spectroscopy. This purified peptide exhibited strong scavenging activity against peroxyl radical (IC50 value, 0.028 mg/mL). In addition, this tetrapeptide showed significant protection ability against AAPH-induced oxidative stress by inhibiting of reactive oxygen species (ROS) generation in Chang liver cells in vitro and in a zebrafish model in vivo. This research suggests that the tetrapeptide derived from Alcalase-proteolytic hydrolysate of velvet antler are excellent antioxidants and could be effectively applied as functional food ingredients and pharmaceuticals.


Subject(s)
Antioxidants/pharmacology , Hepatocytes/drug effects , Hepatocytes/metabolism , Oxidative Stress/drug effects , Peptide Fragments/pharmacology , Subtilisins/chemistry , Animals , Antioxidants/chemistry , Antioxidants/isolation & purification , Antlers/chemistry , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Humans , Hydrolysis , Peptide Fragments/chemistry , Peptide Fragments/isolation & purification , Reactive Oxygen Species/metabolism , Zebrafish
17.
J Food Biochem ; 43(7): e12833, 2019 07.
Article in English | MEDLINE | ID: mdl-31353700

ABSTRACT

Seahorses, Hippocampus abdominalis, have a long history in traditional Chinese medicine as an important healthy ingredient in foods. This study evaluated the antioxidant activity of an enzymatic hydrolysate prepared from a seahorse bred in Jeju, South Korea. Experiments were performed in vitro using electron spin resonance spectrometry (ESR) to determine the free radical scavenging activity and in vivo using a zebrafish model to determine the protective effects against 2,2-azobis hydrochloride (AAPH)-induced oxidative damage. H. abdominalis protein hydrolysate (HPH) exhibited peroxyl radical scavenging activity (IC50  = 0.58 mg/ml) generated by the water-soluble AAPH (azo initiator of peroxyl radicals). HPH reduced dose-dependently both intracellular reactive oxygen species (ROS) levels in AAPH-induced cells and cell death in AAPH-induced zebrafish embryos. The antioxidant peptide purified from HPH was identified as a tripeptide (alanine-glycine-aspartic acid) using Q-TOF ESI mass spectroscopy. Thus, this study demonstrated that HPH contains antioxidant peptides that exhibit a strong antioxidant activity. PRACTICAL APPLICATIONS: Hippocampus abdominalis is one of the largest seahorse species and cultivated in many countries. Because of its large body size compared to other seahorse species, H. abdominalis has acquired considerable consumer attraction in the global market. Owing to its biologically useful properties, it recently gained attention as the natural products obtained from H. abdominalis have varied applications in the field of medicine, health care products, and functional foods. Thus, commercial products of this particular seahorse species are popular among customers, especially in China. The purpose of this study was to evaluate the antioxidant property of H. abdominalism, cultured in a commercial seahorse farm in Jeju Island. Owing to its prominent antioxidant activity, it could be used as an ingredient in medicinal preparations, nutraceuticals, and functional foods.


Subject(s)
Free Radical Scavengers/chemistry , Protein Hydrolysates/pharmacology , Smegmamorpha/metabolism , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Aquaculture , Chlorocebus aethiops , Dietary Supplements , Electron Spin Resonance Spectroscopy , Free Radical Scavengers/pharmacology , Oxidative Stress/drug effects , Peptides/chemistry , Peptides/pharmacology , Protein Hydrolysates/chemistry , Reactive Oxygen Species/metabolism , Spectrometry, Mass, Electrospray Ionization , Subtilisins/chemistry , Subtilisins/pharmacology , Vero Cells , Zebrafish
18.
Mar Drugs ; 17(1)2019 Jan 10.
Article in English | MEDLINE | ID: mdl-30634617

ABSTRACT

The purpose of this study was to investigate the antiobesity effect and the mechanism of action of diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae in 3T3-L1 cells. The antiobesity effects were examined by evaluating intracellular fat accumulation in Oil Red O-stained adipocytes. Based on the results, DPHC dose-dependently inhibited the lipid accumulation in 3T3-L1 adipocytes. DPHC significantly inhibited adipocyte-specific proteins such as SREBP-1c, PPARγ, C/EBP α, and adiponectin, as well as adipogenic enzymes, including perilipin, FAS, FABP4, and leptin in adipocytes. These results indicated that DPHC primarily acts by regulating adipogenic-specific proteins through inhibiting fat accumulation and fatty acid synthesis in adipocytes. DPHC treatment significantly increased both AMPK and ACC phosphorylation in adipocytes. These results indicate that DPHC inhibits the fat accumulation by activating AMPK and ACC in 3T3-L1 cells. Taken together, these results suggest that DPHC can be used as a potential therapeutic agent against obesity.


Subject(s)
Adenylate Kinase/metabolism , Adipocytes/drug effects , Adipogenesis/drug effects , Heterocyclic Compounds, 3-Ring/pharmacology , 3T3-L1 Cells , Adenylate Kinase/genetics , Animals , Cell Survival , Gene Expression Regulation, Enzymologic/drug effects , Heterocyclic Compounds, 3-Ring/chemistry , Mice , Molecular Structure , Seaweed/chemistry
19.
Phytother Res ; 33(3): 737-744, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30570192

ABSTRACT

The aim of the present study was to investigate the effect of 5-bromo-3,4-dihydroxybenzaldehyde (BD) isolated from Polysiphonia morrowii on adipogenesis and differentiation of 3T3-L1 preadipocytes into mature adipocytes and its possible mechanism of action. Levels of lipid accumulation and triglyceride were significantly lower in BD treated cells than those in untreated cells. In addition, BD treatment reduced protein expression levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding proteins α, and sterol regulatory element-binding protein 1 compared with control (no treatment). It also reduced expression levels of adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. AMP-activated protein kinase activation was found to be one specific mechanism involved in the effect of BD. These results demonstrate that BD possesses inhibitory effect on adipogenesis through activating AMP-activated protein kinase signal pathway.


Subject(s)
AMP-Activated Protein Kinases/physiology , Adipogenesis/drug effects , Benzaldehydes/pharmacology , Rhodophyta/chemistry , 3T3-L1 Cells , Animals , Benzaldehydes/isolation & purification , Cell Differentiation/drug effects , Enzyme Activation/drug effects , Lipid Metabolism/drug effects , Mice , Signal Transduction/drug effects
20.
Int J Mol Sci ; 19(9)2018 Sep 10.
Article in English | MEDLINE | ID: mdl-30201926

ABSTRACT

Marine-derived extract and/or bioactive compounds have attracted increasing demand due to their unique and potential uses as cures for various inflammation-based diseases. Several studies revealed anti-inflammatory candidates found in soft corals. However, the effects of soft corals on inflammation in an in vivo model remain to be determined. Therefore, the extract of soft coral Dendronephthya puetteri (DPE) was investigated for an in vivo anti-inflammatory effect in a lipopolysaccharide (LPS)-stimulated zebrafish model to determine its potential use as a natural anti-inflammatory agent. We also investigated whether DPE has toxic effects in a zebrafish model. No significant changes were observed in terms of survival, heart beat rate, or developmental abnormalities in the zebrafish embryos exposed to a concentration below 100 µg/mL of DPE. Treating the zebrafish model with LPS-treatment significantly increased the ROS, NO generation, and cell death. However, DPE inhibited this LPS-stimulated ROS, NO generation, and cell death in a dose-dependent manner. In addition, DPE significantly reduced the mRNA expression of both iNOS and COX-2 and markedly suppressed the expression levels of the proinflammatory cytokines, TNF-α and IL-6, in an LPS-stimulated zebrafish model. These findings demonstrate that DPE has profound anti-inflammatory effect in vivo, suggesting that DPE might be a strong natural anti-inflammatory agent.


Subject(s)
Anthozoa/chemistry , Biological Products/administration & dosage , Inflammation/drug therapy , Lipopolysaccharides/adverse effects , Animals , Biological Products/pharmacology , Cell Death/drug effects , Cytokines/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Down-Regulation , Inflammation/chemically induced , Inflammation/immunology , Oxidative Stress/drug effects , Zebrafish
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