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ABSTRACTS. PHYTOPHARM 2017
INVESTIGATION OF AN ANTI-ACTIVATED FACTOR X (ANTI-XA) ASSAY FOR THE QUANTIFICATION OF FUCOIDAN IN RODENTS PLASMA
© Pozharitskaya O.N.1, Kosman V.M.1, Faustova N.M.1, Obluchinskaya E.D.2, Shikov A.N.1
1 Saint-Petersburg Institute of Pharmacy, Leningrad region, Kuzmolovo, Russia;
2 Federal State Budgetary Scientific Institution of Murmansk Marine Biological Institute, Kola Scientific Center of the Russian Academy of Sciences (MMBI KSC RAS), Murmansk, Russia
Fucoidan is a fucose-rich sulfated polysaccharide mainly found in brown algae of the class Phaeophyceae. It shows a wide range of pharmaceutically important biological activities including anti-inflammatory, anticoagulant, procoagulant, anticancer, and antiviral activities [1]. In this study, a method for determining of fucoidan based on their ant-Xa activity was established. The method was used for the investigation of pharmacokinetic of Fucus vesiculosus fucoidan in rodents after single oral administration.
The brown seaweed F. vesiculosus were collected from the littoral of the Barents Sea (Dalnie Zelentsy, the Murmansk region, Russia) in August 2015 and fucoidan was isolated by the method as described early [2] with some modification.
The anti-Xa activity was analyzed by amidolytic assay using ReaChrom Heparin kit (Renam, Russia) with a lower limit of heparin detection of 0.01 lU/mL. The method was validated by the linearity, limit of detection (LOD), lower limit of quantification (LLOQ), upper limit of quantification (ULOQ) and recovery. Basic pharmacokinetic parameters (Cmax, Tmax MRT and AUC0-10) of fucoidan were calculated by noncompartmental method.
The average molecular mass of the purified fucoidan was about 735 kDa. The polysaccharide has contained
79.5% of neutral carbohydrates, 27.0% sulfate residues and 0.7% of uronic acid. Fucose (73.5 mol %), glucose (11.8 mol %), xylose (6.6 mol %), galactose, mannose, and arabinose were identified by HPLC-RID.
A positive correlation between biological activity and concentration in plasma of rabbits was demonstrated for fucoidan in the dose range 0.1-10 mg/kg and was comparable to heparin.
The method was successfully applied to achieve sensitive detection of fucoidan in the range of 0.1351.083 ^g/mL with <10% intraday precision. Xa standards when frozen immediately after reconstitution could be used for the following 4 months.
The absolute bioavailability of fucoidan was 7.4% for rats and 10.7% for rabbits.
The outcome of this study offers tangible support for the continued development of new effective pharmaceuticals with fucoidan.
References:
1. Fitton JH, Stringer DN, Karpiniec SS. 2015. Mar Drugs. 13(9):5920-5946.
2. Obluchinskaya ED, Makarova MN, Pozharitskaya ON, Shikov AN. 2015. Pharm Chem J. 49(3):183-186.
MARINE DERIVED FUNGI AND NATURAL PRODUCTS -INSPIRATIONS FROM THE SEA
© Peter Proksch, Rainer Kalscheuer
Universität Düsseldorf Institut für Pharmazeutische Biologie und Biotechnologie, Düsseldorf
Marine-derived fungi have been shown to colonize virtually all ecological niches and habitats in the marine environment where they produce a plethora of structurally new bioactive compounds as highlighted in numerous recent reviews. Our own studies on marine-derived fungi focus to a large extent on Mangrove associated fungi that live as endophytes in the tissues of their host plants. Mangroves live at the border between land and sea and are classical inhabitants of coastal swamps in the tropical regions of the world. Geographical hot spots of our research on Mangrove endophytes are in China and in West Africa. Recent
examples of our studies focus on the discovery of fungal natural products that inhibit Mycobacterium tuberculosis which is the causative agent for the often deadly disease Tuberculosis. Once thought to be close to extinction this disease has seen a dramatic comeback in recent years. Approximately one third of the world population is infected with M. tuberculosis which causes an annual death toll of 1-3 million patients per year. Recent years have seen a dramatic increase of multi-resistant strains of M. tuberculosis especially in poor countries of the world. These resistant strains can no longer be treated with the commonly used antibiotics.
Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy]
VOL. 15/2017/SUPPLEMENT 1
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