Jung-Ae Kim

Flavonoid glycosides isolated from Salicornia herbacea inhibit matrix metalloproteinase in HT1080 cells

Flavonoid glycosides, isorhamnetin 3-capital O, Cyrillic-beta-d-glucoside, and quercetin 3-O-beta-d-glucoside were isolated from Salicornia herbacea and their inhibitory effects on matrix metalloproteinase-9 and -2 (MMP-9 and -2) were evaluated in human fibrosarcoma cell line (HT1080). In zymography experiments, these flavonoid glycosides led to the reduction of the expression levels and activities of MMP-9 and -2 without any significant difference between these flavonoid glycosides. Protein expression levels of both MMP-9 and MMP-2 were inhibited and TIMP-1 (tissue inhibitor of metalloproteinase-1) protein level was enhanced by these flavonoid glycosides. Moreover, a transfection study carried out with AP-1 reporter construct revealed that the reporter activity was suppressed by treatment with isorhamnetin 3-capital O, Cyrillic-beta-d-glucoside. Therefore, these results suggested that these flavonoid glycosides have a potential as valuable natural chemopreventive agents for cancer.

Protective effect of isorhamnetin 3-О-β-d-glucopyranoside from Salicornia herbacea against oxidation-induced cell damage

Isorhamnetin 3-O-beta-D-glucopyranoside (1) was isolated from Salicornia herbacea. The inhibitory effects of compound 1 on oxidative stress were evaluated in free-cellular and cellular systems. An increased concentration of compound 1 not only exhibited dose-dependent scavenging activities on the generation of 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl and carbon-centered radicals, but also significantly decreased levels of intracellular reactive oxygen species (ROS) in a dose-dependent manner. Further, antioxidative mechanisms by compound 1 were examined by measuring the intracellular glutathione (GSH) level and expression levels of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione reductase and heme oxygenase-1 (HO-1). Compound 1 significantly elevated GSH level as well as expression levels of antioxidant enzymes which were closely related with amount of cellular ROS. In addition, it significantly inhibited oxidative damage of purified genomic DNA and suppressed activity of myeloperoxidase (MPO), a generator of potent oxidant (hypochlorous acid), in tumor necrosis factor-alpha (TNF-alpha) stimulated human myeloid cells. Therefore, these results suggested that compound 1 has a therapeutic effectiveness in prevention of ROS-induced cellular damage and is a candidate worthy of being developed as a potential natural antioxidant related to oxidative stress.

Anti-obesity effect of sulfated glucosamine by AMPK signal pathway in 3T3-L1 adipocytes

In this study, we investigated the effect of sulfated glucosamine (SGlc) on adipogenesis of 3T3-L1 adipocytes during differentiation of preadipocytes into adipocytes by measuring lipid accumulation and adipogenesis related factors. Treatment with SGlc reduced the triglyceride content in Oil-Red O staining and enhanced glycerol secretion in adipocytes in a dose-dependent manner. In addition, SGlc induced the down-regulation of adipogenesis related factors and adipocyte specific gene promoters. Moreover, treatment of 3T3-L1 adipocytes with SGlc activated the phosphorylated adenosine monophosphate-activated protein kinase (AMPK) alpha and beta along with their substrate, acetyl-CoA carboxylase (ACC). These results suggest that inhibitory effect of SGlc on adipocyte differentiation might be mediated through the up-regulation of AMPK pathway.

1-(3′,5′-dihydroxyphenoxy)-7-(2″,4″,6-trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4-dioxin Inhibits Adipocyte Differentiation of 3T3-L1 Fibroblasts

In this study, we isolated the phloroglucinol derivative, 1-(3′,5′-dihydroxyphenoxy)-7-(2″,4″,6-trihydroxyphenoxy)-2,4,9-trihydroxydibenzo-1,4-dioxin (1), from Ecklonia cava and evaluated its potential inhibition on adipocyte differentiation in 3T3-L1 cells. Lipid accumulation along with the expression of several genes associated with adipogenesis and lipolysis was examined at the end of differentiation. Lipid accumulation level was examined by measuring triglyceride content and Oil-Red O staining. The expression levels of several genes and proteins were examined using reverse-transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and Western blot analysis. Compound 1 significantly reduced lipid accumulation and downregulated peroxisome proliferator-activated receptor-γ, sterol regulatory element-binding protein 1c, and CCAAT/enhancer-binding proteins α in a dose-dependent manner. Moreover, the presence of compound 1 induced downregulation of adipogenic target genes such as fatty acid binding protein 4, fatty acid transport protein 1, fatty acid synthase, acyl-CoA synthetase 1, lipoprotein lipase, and leptin. According to the lipolytic response, compound 1 downregulated perilipin and hormone-sensitive lipase while upregulating tumor necrosis factor alpha. Therefore, these results suggest that compound 1 might decrease lipid accumulation during adipocyte differentiation by modulating adipogenesis and lipogenesis. Furthermore, compound 1 could be developed as a functional agent effective in improving obesity.

Anti-obesity effect of carboxymethyl chitin by AMPK and aquaporin-7 pathways in 3T3-L1 adipocytes

The aim of this study was to investigate the anti-obesity effect of carboxymethyl-chitin (CM-chitin), a water-soluble derivative of chitin, by measuring lipid accumulation and adipogenesis related factors in 3T3-L1 adipocytes. CM-chitin was synthesized by means of carboxymethylation reaction. Its inhibitory effect on lipid accumulation was investigated by measuring triglyceride content and glycerol release level. The gene and protein levels associated with adipogenesis were determined using reverse transcriptase-polymerase chain reaction and Western blot analysis. Treatment with CM-chitin reduced triglyceride content and enhanced glycerol secretion in a dose-dependent manner. CM-chitin induced the down-regulation of adipogenesis related transcriptional factors and adipocyte specific gene promoters. Moreover, the specific mechanism by CM-chitin was confirmed by transcriptional activations of the phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and aquaporin-7. These results suggest that CM-chitin exerts anti-adipogenic effect on lipid accumulation through modulations of AMPK and aquaporin-7 signal pathways.

Phosphorylated glucosamine inhibits adipogenesis in 3T3-L1 adipocytes.

Phosphorylated glucosamine (glucosamine-6-phosphate, PGlc) was synthesized using methanesulfonic acid, phosphorus pentoxide (P(2)O(5)), NH(2)NH(2) and DMF. Its inhibitory effect on lipid accumulation in cultured 3T3-L1 adipocytes was investigated by measuring triglyceride contents and Oil Red O staining. In order to understand the mechanism by which lipid accumulation in adipocytes is decreased by PGlc, we examined the expression levels of several genes and proteins associated with adipogenesis and lipolysis using reverse transcription polymerase chain reaction, real-time polymerase chain reaction and Western blot analysis. Treatment with PGlc significantly reduced lipid accumulation during adipocyte differentiation and induced down-regulation of peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein 1 and CCAAT/enhancer binding protein-alpha in a dose-dependent manner. Moreover, treatment with PGlc during adipocyte differentiation induced significant up-regulation of preadipocyte factor 1 mRNA and down-regulation of such adipocyte-specific gene promoters as adipocyte fatty acid binding protein, fatty acid synthase, lipoprotein lipase and leptin. According to the lipolytic response, PGlc up-regulated hormone-sensitive lipase mRNA expression and suppressed the expression levels of tumor necrosis factor-alpha mRNA compared with fully differentiated adipose tissue. These results suggest that the inhibitory effect of PGlc on adipocyte differentiation might be mediated through the down-regulation of adipogenic transcription factors, such as peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein 1 and CCAAT/enhancer binding protein-alpha, which are related to the downstream adipocyte-specific gene promoters.

Bioactive peptides from marine sources as potential anti-inflammatory therapeutics.

Marine organisms are important sources for bioactive molecules that have been developed into treatments for various diseases. The unusual marine environment associated with chemical diversity constitutes an actually unlimited resource of new active substances in the field of the development of bioactive products. In this review, the molecular diversity of marine peptides is described as well as information about their anti-inflammatory properties and mechanisms of action. Moreover, novel bioactive peptides from sponges, bacterium and microalgae are also described with their pharmacological effects in relation with anti-inflammation.

The chromene sargachromanol E inhibits ultraviolet A-induced ageing of skin in human dermal fibroblasts.

Background  Skin ageing is influenced by environmental factors such as ultraviolet (UV) radiation. The effects of UV radiation on skin functions should be investigated using human in vitro models to understand the mechanisms of skin ageing. Additionally, marine algae provide a valuable source for identifying and extracting biologically active substances.

Bioactive quinone derivatives from the marine brown alga Sargassum thunbergii induce anti-adipogenic and pro-osteoblastogenic activities.

BACKGROUND Health problems related to the lack of bone formation are a major problem for ageing populations in the modern world. As a part of the ongoing trend to develop natural substances that attenuate bone loss in osteoporosis, the effects of the edible brown alga Sargassum thunbergii and its active contents on adipogenic differentiation in 3T3-L1 fibroblasts and osteoblast differentiation in MC3T3-E1 pre-osteoblasts were evaluated. RESULTS Treatment with S. thunbergii significantly reduced lipid accumulation and expression of adipogenic differentiation markers such as peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α and sterol regulatory element binding protein 1c. In addition, S. thunbergii successfully enhanced osteoblast differentiation as indicated by increased alkaline phosphatase activity along raised levels of osteoblastogenesis indicators, namely bone morphogenetic protein-2, osteocalcin and collagen type I. Two compounds, sargaquinoic and sargahydroquinoic acid, were isolated from active extract and shown to be active by means of osteogenesis inducement. CONCLUSION S. thunbergii could be a source for functional food ingredients for improved treatment of osteoporosis and obesity.

Phosphorylated glucosamine inhibits the inflammatory response in LPS-stimulated PMA-differentiated THP-1 cells

This study evaluated the effect of phosphorylated glucosamine (pGlc) on the regulation of cytokines involved in immunological activities. Changes in the inflammatory profiles of lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage models were investigated following pGlc treatment. Treatment with pGlc inhibited the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6). In addition, pGlc suppressed the regulation of inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) in LPS-stimulated THP-1 macrophages. Furthermore, we confirmed that the LPS-stimulated transcription of MAP kinases in PMA-differentiated THP-1 macrophages was inhibited by pGlc. According to this study, pGlc can be considered as a potential anti-inflammatory agent.