The Pharmacokinetics of Fucoidan after Topical Application to Rats

Fucoidan, a fucose-rich polysaccharide from brown algae, has been used for transdermal formulations targeting inflammatory skin conditions, for the treatment of thrombosis, vascular permeability diseases, subcutaneous wounds, and burns. However, the pharmacokinetics of fucoidan after topical application has not been described. In this study, an ointment (OF) containing 15% fucoidan was topically applied to rats at the doses of 50–150 mg/g. The anti-Xa activity was selected as the biomarker, and the amidolytic assay method was validated and applied for pharmacokinetic studies of fucoidan. Fucoidan in OF penetrated the skin and distributed into the skin, striated muscle, and plasma with AUC0–48 = 0.94 μg·h/g, 2.22 μg·h/g, and 1.92 µg·h/mL, respectively. The longest half-life for fucoidan was observed in plasma, then in striated muscle and skin. It was found that the pharmacokinetics of fucoidan after topical OF application was linear, in the range of 50–150 mg/kg. No accumulation of fucoidan in plasma was observed after repeated topical applications of 100 mg/kg during five days. Our results support the rationality of topical application of formulations with fucoidan

The Pharmacokinetics of Fucoidan after Topical Application to Rats

Fucoidan, a fucose-rich polysaccharide from brown algae, has been used for transdermal formulations targeting inflammatory skin conditions, for the treatment of thrombosis, vascular permeability diseases, subcutaneous wounds, and burns. However, the pharmacokinetics of fucoidan after topical application has not been described. In this study, an ointment (OF) containing 15% fucoidan was topically applied to rats at the doses of 50–150 mg/g. The anti-Xa activity was selected as the biomarker, and the amidolytic assay method was validated and applied for pharmacokinetic studies of fucoidan. Fucoidan in OF penetrated the skin and distributed into the skin, striated muscle, and plasma with AUC0–48 = 0.94 μg·h/g, 2.22 μg·h/g, and 1.92 µg·h/mL, respectively. The longest half-life for fucoidan was observed in plasma, then in striated muscle and skin. It was found that the pharmacokinetics of fucoidan after topical OF application was linear, in the range of 50–150 mg/kg. No accumulation of fucoidan in plasma was observed after repeated topical applications of 100 mg/kg during five days. Our results support the rationality of topical application of formulations with fucoidan

Pharmacokinetic and Tissue Distribution of Fucoidan from Fucus vesiculosus after Oral Administration to Rats

Fucus vesiculosus L., known as bladderwrack, belongs to the brown seaweeds, which are widely distributed throughout northern Russia, Atlantic shores of Europe, the Baltic Sea, Greenland, the Azores, the Canary Islands, and shores of the Pacific Ocean. Fucoidan is a major fucose-rich sulfated polysaccharide found in Fucus (F.) vesiculosus. The pharmacokinetic profiling of active compounds is essential for drug development and approval. The aim of the study was to evaluate the pharmacokinetics and tissue distribution of fucoidan in rats after a single-dose oral administration. Fucoidan was isolated from F. vesiculosus. The method of measuring anti-activated factor X (anti-Xa) activity by amidolytic assay was used to analyze the plasma and tissue concentrations of fucoidan. The tissue distribution of fucoidan after intragastric administration to the rats was characterized, and it exhibited considerable heterogeneity. Fucoidan preferentially accumulates in the kidneys (AUC(0-t) = 10.74 mu g.h/g; C-max = 1.23 mu g/g after 5 h), spleen (AUC(0-t) = 6.89 mu g.h/g; C-max = 0.78 mu g/g after 3 h), and liver (AUC(0-t) = 3.26 mu g.h/g; C-max = 0.53 mu g/g after 2 h) and shows a relatively long absorption time and extended circulation in the blood, with a mean residence time (MRT) = 6.79 h. The outcome of this study provides additional scientific data for traditional use of fucoidan-containing plants and offers tangible support for the continued development of new effective pharmaceuticals using fucoidan.Peer reviewe

In Vitro Anti-Inflammatory Activities of Fucoidans from Five Species of Brown Seaweeds

This study aimed to compare the anti-inflammatory effects of fucoidans from brown seaweeds (Saccharina japonica (SJ), Fucus vesiculosus (FV), Fucus distichus (FD), Fucus serratus (FS), and Ascophyllum nodosum (AN)), and determine the relationship between composition and biological activity. The anti-inflammatory activity was tested in vitro. It is believed that inflammation could be triggered by free radicals. Fucoidans from F. vesiculosus (FV1 and FV3) showed the strongest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with an IC50 = 0.05 mg/mL. In the total antioxidant capacity (TAC) test, the activity was concentration-dependent. Notable, the TAC of fucoidans except samples of FV2 and SJ (which have a lower phenolic content) was higher than that of phloroglucinol. The TAC of fucoidans strongly and positively correlated with polyphenol content. A weak correlation was associated with xylose content. The synergistic effect for fucoidans was calculated for the first time using carbohydrates and polyphenols as model mixtures. The synergy in the DPPH test was found only for FV1 and FV3 (mixture effect ME = 2.68 and 2.04, respectively). The ME strongly positively correlated with polyphenols. The relationship of ME with fucose content was positive but moderate. It was first established that the anti-inflammatory effects of fucoidan could be mediated via the inhibition of protein denaturation. The inhibition was concentration-dependent and strongly correlated with the fucose content and moderate with sulfate content. The purified fucoidan FV2 showed the most promising activity (IC50 = 0.20 mg/mL vs. IC50 = 0.37 mg/mL for diclofenac sodium). Similar relations were also observed in the membrane protection model. Fucoidans were able to stabilize the cell membrane integrity of human red blood corpuscles (HRBC). The results of our study support the rationality of fucoidan use as a promising agent for the treatment of inflammatory-related diseases via mechanisms of radical scavenging, antioxidant activity, inhibition of protein denaturation, and HRBC membrane stabilization

Mechanisms of Bioactivities of Fucoidan from the Brown Seaweed Fucus vesiculosus L. of the Barents Sea

The aim of this study was to elucidate some mechanisms of radical scavenging and the anti-inflammatory, anti-hyperglycemic, and anti-coagulant bioactivities of high molecular weight fucoidan from Fucus vesiculosus in several in vitro models. Fucoidan has displayed potent 1, 1-diphenyl-2-picryl hydrazil radical scavenging and reduction power activities. It significantly inhibits the cyclooxygenase-2 (COX-2) enzyme (IC50 4.3 μg mL−1) with a greater selectivity index (lg(IC80 COX-2/IC80COX-1), −1.55) than the synthetic non-steroidal anti-inflammatory drug indomethacin (lg(IC80 COX-2/IC80COX-1), −0.09). A concentration-dependent inhibition of hyaluronidase enzyme with an IC50 of 2.9 μg mL−1 was observed. Fucoidan attenuated the lipopolysaccharide-induced expression of mitogen-activated protein kinase p38. Our findings suggest that the inhibition of dipeptidyl peptidase-IV (DPP-IV) (IC50 1.11 μg mL−1) is one of the possible mechanisms involved in the anti-hyperglycemic activity of fucoidan. At a concentration of 3.2 μg mL−1, fucoidan prolongs the activated partial thromboplastin time and thrombin time by 1.5-fold and 2.5-fold compared with a control, respectively. A significant increase of prothrombin time was observed after the concentration of fucoidan was increased above 80 μg mL−1. This evidenced that fucoidan may have an effect on intrinsic/common pathways and little effect on the extrinsic mechanism. This study sheds light on the multiple pathways of the bioactivities of fucoidan. As far as we know, the inhibition of hyaluronidase and DPP-IV by high molecular fucoidan was studied for the first time in this work. Our results and literature data suggest that molecular weight, sulfate content, fucose content, and polyphenols may contribute to these activities. It seems that high molecular weight fucoidan has promising therapeutic applications in different pharmacological settings. Anti-oxidant, anti-inflammatory and anti-coagulant drugs have been used for the management of complications of COVID19. Taken as a whole, fucoidan could be considered as a prospective candidate for the treatment of patients with COVID19; however, additional research in this field is required

Formulation, Optimization and In Vivo Evaluation of Fucoidan-Based Cream with Anti-Inflammatory Properties

Fucoidan is a polysaccharide found in brown alga with glorious potential for pharmacological activities, among which its anti-inflammatory properties have gained meaningful attention. Due to several advantages of formulations for topical application, this study aimed to develop and optimize a fucoidan-based cream formulation and to investigate its anti-inflammatory potential after topical application in vivo. Fucoidan from Fucus vesiculosus L. was used. The cream base consisting of olive oil and Kolliphor RH40 was optimized followed by in vitro agar diffusion and drug release studies. The fucoidan-based cream with 13% Kolliphor P 407, 1% Transcutol P, and 5% PEG400 showed good spreadability, washability, and colloidal stability, and it did not irritate the skin. The kinetics of fucoidan release from the optimized cream exhibited the best fit to the Korsmeyer–Peppas and Higuchi models with R2 > 0.99. Fucoidan release was controlled by drug diffusion and anomalous transport provided by the optimized cream base. The formulation was stable and provided high fucoidan release after storage for 1 year. Topical application of the fucoidan-based cream dose-dependently inhibited carrageenan-induced edema and ameliorated mechanical allodynia in rats. The efficacy of the fucoidan-based cream at a high dose was comparable with the efficacy of diclofenac gel. The fucoidan-based cream could be considered a promising anti-inflammatory formulation

Community Structure and Abiotic Characteristics of Pelagic Microalgal in Adjacent Areas of the Barents Sea and Kara Sea

This study aimed to confirm the hypothesis of a floristic identity between the southeastern Barents Sea and the southwestern Kara Sea. We conducted integrated studies of pelagic microalgae communities including microscope cell counting and taxonomical identification as well as photosynthetic pigments determination and defining of hydrological and hydrochemical characteristics during a cruise in late August and the first half of September 2020. As far as we are concerned, no such observations had been carried out in this region at this time of the year before. During our observations, 35 species were identified, 14 (40%) of which were present in both water bodies. The communities of both regions were in a state corresponding to the autumn stage of the annual succession cycle. In the southeastern Barents Sea, the mean abundance of organisms in the water column varied from 10.650 to 41.840 cells per liter with a biomass of 71.04 to 300.55 µg/L. In the southwestern Kara Sea, these values were 3.510–28.420 cell/L and 16.31–66.96 µg/L, respectively. In general, the results of a comparative analysis suggest that the pelagic algal communities in the regions under comparison, despite the difference in hydrological parameters, demonstrate similar qualitative and quantitative characteristics and thus may belong to the same phytogeographic region

Rheological Properties of Fish Gelatin Modified with Sodium Alginate

Polyelectrolyte complexes of sodium alginate and gelatin obtained from cold-blooded fish were studied for potential application as structure-forming agents in food hydrogels. The mass ratio of sodium alginate to gelatin plays a decisive role in the sol-gel transition and rheological behavior of the complexes. Differences in the sol-gel transition temperature were observed upon heating and cooling, as is typical for such materials. We investigated the characteristics of this transition by measuring the isothermal changes in the elastic modulus over time at a constant frequency and the transition temperature at a range of frequencies. The kinetic nature of this transition depends on the composition of the complexes. A characteristic alginate-gelatin mass ratio is the ratio at which maximum transition temperature as well as elastic modulus and viscosity (rheological parameters) values are obtained; the characteristic mass ratio for these complexes was found to be 0.06. Calculation of the ionic group ratios in the biopolymers that form complexes and comparison of these data with the turbidimetric titration results clarified the origin of these maxima. Measuring the viscoelastic properties and the creep-elastic recoil of the samples allowed us to characterize these materials as viscoelastic media with a viscosity in the order of 103–104 Pa·s and an elastic modulus in the order of 102–103 Pa. These values drastically decrease at a certain stress threshold, which can be treated as the gel strength limit. Therefore, the observed rheological behavior of gels formed by fish gelatin modified with sodium alginate characterizes them as typical viscoelastic soft matter

Community Structure and Abiotic Characteristics of Pelagic Microalgal in Adjacent Areas of the Barents Sea and Kara Sea

This study aimed to confirm the hypothesis of a floristic identity between the southeastern Barents Sea and the southwestern Kara Sea. We conducted integrated studies of pelagic microalgae communities including microscope cell counting and taxonomical identification as well as photosynthetic pigments determination and defining of hydrological and hydrochemical characteristics during a cruise in late August and the first half of September 2020. As far as we are concerned, no such observations had been carried out in this region at this time of the year before. During our observations, 35 species were identified, 14 (40%) of which were present in both water bodies. The communities of both regions were in a state corresponding to the autumn stage of the annual succession cycle. In the southeastern Barents Sea, the mean abundance of organisms in the water column varied from 10.650 to 41.840 cells per liter with a biomass of 71.04 to 300.55 µg/L. In the southwestern Kara Sea, these values were 3.510–28.420 cell/L and 16.31–66.96 µg/L, respectively. In general, the results of a comparative analysis suggest that the pelagic algal communities in the regions under comparison, despite the difference in hydrological parameters, demonstrate similar qualitative and quantitative characteristics and thus may belong to the same phytogeographic region

The Impact of Natural Deep Eutectic Solvents and Extraction Method on the Co-Extraction of Trace Metals from <i>Fucus vesiculosus</i>

In recent years, natural deep eutectic solvents (NADES) have been widely investigated for the extraction of food and medicinal plants as well as seaweeds. However, the ability of NADES for trace elements co-extraction from natural sources is not well investigated. The aim of this study was to investigate the ability of common NADES for trace elements co-extraction from Fucus vesiculosus. All of the tested NADES did not recover As and Co (concentration 2O (5:3:1) provided the lowest contents of all elements, and the highest extracted amounts were obtained employing water contents of 60–80%. The calculated daily intake of all the elements contained in NADES extracts were less than the daily dose risk estimators. The hazard quotients, hazard indexes, and carcinogenic risk calculated for all trace elements and their combination were considerably less than 1. This evidences no health risk, and carcinogenic risk after topical application of all studied NADES. For the first time, the results of the current study demonstrated that NADES extracts of F. vesiculosus contain a lower amount of trace metals and are safer than the extracts obtained with water and 70% acetone. This indicates a significant advantage for NADES compared with the other solvents