Fatih Karadeniz

Anti-HIV-1 activity of low molecular weight sulfated chitooligosaccharides.

Chitooligosaccharides are nontoxic and water-soluble compounds obtained by enzymatic degradation of chitosan, which is derived from chitin by a deacetylation process. Chitooligosaccharides possess broad range of activities such as antitumour, antifungal, antibacterial activities. Sulfated chitooligosaccharides (SCOSs) with different molecular weights were synthesized by a random sulfation reaction. In the present study, anti-HIV-1 properties of SCOSs and the impact of molecular weight on their inhibitory activity were investigated. SCOS III (MW 3-5 kDa) was found to be the most effective compound to inhibit HIV-1 replication. At nontoxic concentrations, SCOS III exhibited remarkable inhibitory activities on HIV-1-induced syncytia formation (EC(50) 2.19 microg/ml), lytic effect (EC(50) 1.43 microg/ml), and p24 antigen production (EC(50) 4.33 microg/ml and 7.76 microg/ml for HIV-1(RF) and HIV-1(Ba-L), respectively). In contrast, unsulfated chitooligosaccharides showed no activity against HIV-1. Furthermore, it was found that SCOS III blocked viral entry and virus-cell fusion probably via disrupting the binding of HIV-1 gp120 to CD4 cell surface receptor. These results suggest that sulfated chitooligosaccharides represent novel candidates for the development of anti-HIV-1 agent.

Biological importance and applications of squalene and squalane.

Squalene is a polyunsaturated hydrocarbon with a formula of C₃₀H₅₀. Squalene can be found in certain fish oils, especially shark liver oil, in high amounts and some vegetable oils in relatively smaller amounts. Human sebum also contains 13% squalene as one of its major constituents. Squalane is a saturated derivative of squalene and also found in these sources. Interest in squalene has been raised after its characterization in shark liver oil which is used as a traditional medicine for decades. Several studies exhibited results that prove certain bioactivities for squalene and squalane. Up to date, anticancer, antioxidant, drug carrier, detoxifier, skin hydrating, and emollient activities of these substances have been reported both in animal models and in vitro environments. According to promising results from recent studies, squalene and squalane are considered important substances in practical and clinical uses with a huge potential in nutraceutical and pharmaceutical industries.

Anti-HIV Activity of Extracts and Compounds from Marine Algae

In recent years, elucidation of novel bioactive substances from different marine organisms is gaining importance rapidly not only from the research and publications but also from controlled clinical studies of natural product-derived substances. They offer important leads for the development of antiviral drugs against viral infections caused by human immunodeficiency virus type 1 (HIV-1). Regarding this issue, numerous anti-HIV-1 therapeutic agents from marine resources have been reported for their potential medicine/medical application as novel functional ingredients in anti-HIV therapy. In detail, marine macroalgae have attracted much of attention as a reliable source for potential anti-HIV compounds. Up to date, several types of compounds such as tannins, polysaccharides, lectins, and derivatives have been isolated, identified, and reported to possess significant anti-HIV-1 activity.

Antioxidant peptides from protein hydrolysate of microalgae Navicula incerta and their protective effects in HepG2/CYP2E1 cells induced by ethanol.

Marine microalgae have been reported as valuable new sources of pharmacologically active compounds and there are now numerous commercial applications of microalgae. Hence, in this study we evaluated the protective effects of peptides purified from marine microalgae, Navicula incerta, against alcohol‐induced damage in HepG2/CYP2E1 cells. To obtain bioactive peptides from microalgae, N. incerta was hydrolysed using various enzymes (alcalase, α‐chymotrypsin, neutrase, papain, pepsin, pronase‐E and trypsin), and the hydrolysates were evaluated for cytoprotective activity. Among them, papain‐derived hydrolysate exhibited higher antioxidant activities than those of other enzymes. Therefore, papain hydrolysate was purified in order to obtain potent antihepatotoxic and antioxidative peptides. The amino acid sequences of the purified peptides were analysed as; NIPP‐1 (Pro‐Gly‐Trp‐Asn‐Gln‐Trp‐Phe‐Leu) with molecular mass 1 171 Da, and NIPP‐2 (Val‐Glu‐Val‐Leu‐Pro‐Pro‐Ala‐Glu‐Leu) with molecular mass 1108 Da. Furthermore, this study demonstrated that NIPP‐1 and NIPP‐2 peptides inhibited ethanol‐induced cytotoxicity in HepG2/CYP2E1 cells. Copyright

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.

Hepatic Fibrosis Inhibitory Effect of Peptides Isolated from Navicula incerta on TGF-β1 Induced Activation of LX-2 Human Hepatic Stellate Cells

In this study, novel peptides (NIPP-1, NIPP-2) derived from Navicula incerta (microalgae) protein hydrolysate were explored for their inhibitory effects on collagen release in hepatic fibrosis with the investigation of its underlying mechanism of action. TGF-β1 activated fibrosis in LX-2 cells was examined in the presence or absence of purified peptides NIPP-1 and NIPP-2. Besides the mechanisms of liver cell injury, protective effects of NIPP-1 and NIPP-2 were studied to show the protective mechanism against TGF-β1 stimulated fibrogenesis. Our results showed that the core protein of NIPP-1 peptide prevented fibril formation of type I collagen, elevated the MMP level and inhibited TIMP production in a dose-dependent manner. The treatment of NIPP-1 and NIPP-2 on TGF-β1 induced LX-2 cells alleviated hepatic fibrosis. Moreover, α-SMA, TIMPs, collagen and PDGF in the NIPP-1 treated groups were significantly decreased. Therefore, it could be suggested that NIPP-1 has potential to be used in anti-fibrosis treatment.

Anti-adipogenic and Pro-osteoblastogenic Activities of Spergularia marina Extract

For decades, Spergularia marina, a local food that is popular in South Korea, has been regarded as a nutritious source of amino acids, vitamins, and minerals. While several halophytes are reported to possess distinct bioactivities, S. marina has yet to be promoted as a natural source of bioactives. In this study, the effects of S. marina on the adipogenic differentiation of 3T3-L1 fibroblasts and the osteoblastic differentiation of MC3T3-E1 pre-osteoblasts and C2C12 myoblast cells were evaluated. The anti-adipogenic effect of S. marina was assessed by measuring lipid accumulation and adipogenic differentiation marker expression. S. marina treatment significantly reduced lipid accumulation and notably decreased the gene levels of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and sterol regulatory element binding protein 1c. In addition, S. marina enhanced osteoblast differentiation, as indicated by increased alkaline phosphatase activity and increased levels of osteoblastogenesis indicators, namely bone morphogenetic protein-2, osteocalcin, and type I collagen. In conclusion, S. marina could be a source of functional food ingredients that improve osteoporosis and obesity. Further studies, including activity-based fractionation, will elucidate the mechanism of action and active ingredients of S. marina, which would provide researchers with a better understanding of the nutraceutical and therapeutic applications of S. marina.

Effect of Salicornia herbacea on Osteoblastogenesis and Adipogenesis in Vitro

Bone-related complications are among the highest concerning metabolic diseases in the modern world. Bone fragility and susceptibility to fracture increase with age and diseases like osteoporosis. Elevated adipogenesis in bone results in osteoporosis and loss of bone mass when coupled with lack of osteoblastogenesis. In this study the potential effect of Salicornia herbacea extract against osteoporotic conditions was evaluated. Adipogenesis inhibitory effect of S. herbacea has been evidenced by decreased lipid accumulation of differentiating cells and expression levels of crucial adipogenesis markers in 3T3-L1 pre-adipocytes. S. herbacea treatment reduced the lipid accumulation by 25% of the control. In addition, mRNA expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α and sterol regulatory element binding protein (SREBP)1c were inhibited by the presence of S. herbacea. Bone formation enhancement effect of S. herbacea was also confirmed in MC3T3-E1 pre-osteoblasts. The presence of S. herbacea significantly elevated the alkaline phosphatase (ALP) activity by 120% at a concentration of 100 μg/mL in differentiating osteoblasts. S. herbacea also significantly increased the expression of osteoblastogenesis indicators, ALP, bone morphogenetic protein (BMP)-2, osteocalcin and collagen type I (collagen-I). In conclusion, S. herbacea possess potential to be utilized as a source of anti-osteoporotic agent that can inhibit adipogenesis while promoting osteoblastogenesis.

Anti-HIV activities of novel synthetic peptide conjugated chitosan oligomers.

Chitosan and chitosan derived compounds are marine byproducts which have been shown to exhibit bioactivities including antibacterial, antioxidant, antidiabetic and anti-HIV. Proteins are among the most potent and selective molecules offering an endless potential of different structure and sequence preferences. The tripeptides which consist of tryptophan (W), methionine (M) and glutamine (Q) have been conjugated with chitosan oligomers. Among them QMW-COS and WMQ-COS protected C8166 cells from cell-lytic effects of HIV-1RF strain. Furthermore, these two compounds inhibited HIV-induced syncytia formation. We confirmed the decrease in viral-load in cell culture using p24 ELISA assay. To determine the specific mode of action of QMW-COS and WMQ-COS to inhibit HIV, we checked the inhibitory action of these compounds on viral reverse transcriptase and protease enzymes. However, we could not detect any inhibitory activity of conjugated compounds on recombinant reverse transcriptase and protease enzyme in vitro. When we co-cultured HIV-infected and uninfected C8166 cells, these two compounds actively inhibited the syncytia formation upon co-culture assay. Time-dependent addition of compounds and finally gp120-CD4 ELISA assay revealed that QMW-COS and WMQ-COS are bioactive compounds inhibiting HIV-induced cytopathic effects via exerting their effects on HIV entry stage.

Antidiabetic Activities of Chitosan and Its Derivatives: A Mini Review

Obesity and diabetes are two important closely related matters to world health with increasing morbidity and mortality rate. Many recent studies promoted chitosan-based substances as lead molecules for treatment and prevention of obesity, diabetes, and related complications due to their easy and potential utilization in the food, pharmaceutical, agricultural, and environmental fields. Although detailed action mechanism and how chitosan-based molecules act as antidiabetics and antiobesity specifically are remain to be enlightened, studies exhibited enough evidence to direct our intention to produce natural therapeutic agents using chitosan and its derivatives as lead substances. In this chapter, some reported antidiabetics and antiobesity applications of chitosan and its derivatives have been briefly summarized in regard to acting pathways and structure-based activity in order to obtain some valuable insights into novel chitosan-based derivatives and their utilization for antidiabetic and antiobesity purposes.