• Molecules and Cells
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• v.19 no.3
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• pp.350-355
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• 2005

Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Heparin can bind to P-selectin, and its anti-inflammatory property is mainly due to inhibition of P-selectin. However, the strong anticoagulant activity of heparin limits its clinical use. We prepared periodate-oxidized, borohydride-reduced heparin (RO-heparin) by chemical modification and tested its anticoagulant and anti-inflammatory activities. Activated partial thromboplastin time (aPTT) assays showed that, compared with heparin, RO-heparin had greatly reduced anticoagulant activity. Intravenous administration of this compound led to reduction in the peritoneal infiltration of neutrophils in a mouse acute inflammation model. In vitro cell adhesion experiments demonstrated that the effect of RO-heparin on inflammatory responses was mainly due to inhibiting the interaction of P-selectin with its ligands. These results indicate that RO-heparin may be a safer treatment for inflammation than heparin, especially when selectin is targeted.

• Macromolecular Research
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• v.17 no.2
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• pp.79-83
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• 2009

The oral delivery of heparin is the preferred therapy in the treatment of patients with a high risk of deep vein thrombosis and pulmonary embolism. New conjugates of heparin and sodium deoxycholate were synthesized in order to enhance the heparin absorption in the GI tract. After oral administration of DOC-heparin, the concentration in anti-FXa assay was increased with increasing amount of coupled DOC. The maximum concentration of DOC-heparin VIII conjugate was $3.3{\pm}0.5\;IU/mL$ at an oral dose of 10 mg/kg, which was 3-fold higher than the baseline level. Finally, DOC coupled to heparin greatly enhanced the absorption of heparin in the GI tract, and this enhancing effect was not induced by changing the tissue structure of the GI wall.

• Toxicological Research
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• v.23 no.2
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• pp.159-164
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• 2007

Toxicity screening of a newly developed oral heparin derivative were carried out in 6 male cynomolgus monkeys (Macaca fascicularis), composed of a treatment group and vehicle control group. A newly orally active heparin derivative, developed by Seoul National University, was once given to treatment group at dose of 500 mg/kg. A treatment group did not show any change in body weights, hematological parameters including platelet-related varivables (platelet, PDW, PCT, MPV) and serum biochemical parameters (e.g., AST, ALT, BUN, etc.) for 2 weeks compared with those of vehicle control group. We also confirmed the maximum plasma concentration (Cmax, 1.73 IU/ml) and the time (Tmax, 1 hr) to reach Cmax. The present study will be valuable in the proper interpretation for nonclinical study using cynomolgus monkeys in the development of new drug of heparin derivative.

• Journal of Nutrition and Health
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• v.17 no.4
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• pp.297-304
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• 1984

The effect of dietary fish oil ( mackerel oil : MO, eel oil : EO) on energy utilization in rats was studied with measurements of various tissue lipoprotein lipase( LPL ) and live and heart mitochondrial respiration. Fatty acid composition of mitrochondrial inner membrane matrix was also investigated. Dietary fat level was 10%( w/w) and reference groups were fed soybean oil (SO), repeseed oil ( RO) and beef tallow( BT ). Activity of LPL was about 60% higher in post-heparin plasma and 2 to 3 times higher in adipose tissue of BT group than fish oil or vegetable oil group. But there was no significant difference between fish oil and vegetable oil groups. Inclusion of EO above 2% (w/w) in dietary fat with fille oil of BT, markedly reduced both post -heparin plasma and adipose tissue LPL. Effects of MO and EO were not different in adipose tissue LPL, but EO was more effective than MO, in reducing post -heparin plasma LPL when mixed fat with varying amount of fish oil was used. Hepatic mitochondria isolated from fish oil-fed group showed the lowest rate of respiration but had P/O ratio comparable to SO and BT groups. On the other hand, cardiac mitochondria of fish oil group showed no difference in all the mitochondrial respiration parameters observed RO group had lowest P/O ratio both in hepatic and cardiac mitochondria. Fatty acid compositions of mitochondrial lipid differ between SO, RO, BT and MO groups, notably in the content of $C_{22:1}$ fatty acid.

• Archives of Pharmacal Research
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• v.28 no.9
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• pp.1037-1041
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• 2005

Geranium (Pelargonium inquinans Ait) leaves were extracted with $80\%$ MeOH, and partitioned into n-hexane, ethyl acetate, BuOH and $H_2O$ to isolate the anticoagulant principles. The EtOAc fraction was found to be the most active, and was further purified using silica and octadecylisilane column chromatography employing a bioassay-guided fractionation method. The active compound was isolated and identified as $1,2,3,4,6-pentagalloyl-\beta-D-glucopyranose$(PGG) (compound I). The isolated anticoagulant significantly prolonged the activated partial thrombin time (APTT) and thrombin time (TT) using normal human plasma. One microgram of $1,2,3,4,6-pentagalloyl-\beta-D-glucopyranose$ showed 0.063 heparin units in the APTT and 2.73 heparin units in the TT for anti-thrombosis. This is the first report of the isolation of PGG from geranium plants.

• Journal of Microbiology and Biotechnology
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• v.13 no.6
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• pp.897-905
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• 2003

Phospholipase D (PLD) and ADP-ribosylation factor (ARF) were partially purified on a series of column chromatography, and their biochemical properties were characterized to understand the regulatory mechanism of PLD activation by ARF protein in the antigen-induced immune responses in guinea pigs. Heparin Sepharose and high-Q Sepharose column chromatographies were used for the purification of PLD, and Sephadex G-25, DEAE Sephacel, Source 15 PHE (HIC), Superdex-75, and Uno-Q column chromatographies were used for the purification of ARF. The purified PLD and ARF proteins were identified with anti-rabbit PLD- or ARF-specific antibodies, showing about 64 or 85 kDa for the molecular mass of PLD and 29 or 35 kDa for the sizes of ARF. Partial cDNA of ARF3 was cloned by RT-PCR in guinea pig lung tissue and its nucleotides and amino acids were sequenced. Guinea pig ARF3 showed 92% of nucleotides sequence identity and 100% of amino acid sequence homology with human ARF3. The ARF-regulated PLD activity was measured in the oleate or ARFs-containing mixed lipid vesicles. The purified and recombinant ARF (rARF) activities were assessed with the $GTP{\gamma}S$ binding assay. The PLD activity was induced by oleate in a dose-dependent manner. The purified ARF and recombinant ARF3 increased PLD activity in guinea pig lung tissues. These data show that the activity of membrane-bound PLD can be regulated by the cytosolic ARF proteins, suggesting that ARF proteins in guinea pig lung can act as a regulatory factor in controlling the PLD activity in allergic reaction.