Anticoagulant Activity Research Articles

Curcumin in Cancer Prevention: Insights from Clinical Trials and Strategies to Enhance Bioavailability.

Cancer remains a leading cause of death worldwide, and current cancer drugs often have high costs and undesirable side effects. Additionally, the development of drug resistance can reduce their effectiveness over time. Natural products have gained attention as potential sources for the treatment and prevention of various diseases. Curcumin, an extract from turmeric (Curcuma longa), is a natural phenolic compound with diverse pharmacological properties, including antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, antiprotozoal, antidiabetic, antivenom, antiulcer, anticarcinogenic, antimutagenic, anticoagulant, and antifertility activities. Given the increasing interest in curcumin for cancer prevention, this review aims to comprehensively examine clinical trials investigating the use of curcumin in different types of cancer. Additionally, effective techniques and approaches to enhance the bioavailability of curcumin are discussed and summarized. This review article provides insights into the properties of curcumin and its potential as a future anticancer drug.

Mucin-Inspired Polymeric Fibers for Herpes Simplex Virus Type 1 Inhibition.

Mucus lines the epithelial cells at the biological interface and is the first line of defense against multiple viral infections. Mucins, the gel-forming components of mucus, are high molecular weight glycoproteins and crucial for preventing infections by binding pathogens. Consequently, mimicking mucins is a promising strategy for new synthetic virus inhibitors. In this work, synthetic mucin-inspired polymers (MIPs) as potential inhibitors of herpes simplex virus 1 (HSV-1) are investigated. By using a telechelic reversible addition-fragmentation chain-transfer (RAFT) polymerization technique, a new dendronized polysulfatep(G1AAm-OSO3)PDSwith an amide-backbone similar to the native mucin glycoproteins is synthesized.p(G1AAm-OSO3)PDSshows mucin-like elongated fiber structure, as revealed in cryo-electron microscopy (cryo-EM) imaging, and its HSV-1 inhibition activity together with its previously reported methacrylate analoguep(G1MA-OSO3)PDS is tested. Both of the sulfated MIPs show strong HSV-1 inhibition in plaque reduction assays with IC50 values in lower nanomolar range (<3× 10-9 m) and demonstrate a high cell compatibility (CC50>1.0mgmL-1) with lower anticoagulant activity than heparin. In addition, the prophylactic and therapeutic activity of both MIPs is assessed in pre- and post-infection inhibition assays and clearly visualize their high potential for application using fluorescent microscopy imaging of infected cells.

Structure and pharmacokinetics/pharmacodynamics of the anticoagulant tetradecasaccharide oHG-14 as an intrinsic tenase inhibitor

The intrinsic tenase complex (iXase) is an attractive antithrombotic target to treat or prevent pathological thrombosis with negligible bleeding risk. Fucosylated glycosaminoglycan (FG) is a promising anticoagulant by inhibiting iXase. A depolymerized FG (dHG-5) as an anticoagulant has been approved for clinical trials. Given that dHG-5 is a multi-component drug candidate consisting of a homologous series of oligosaccharides, it is difficult to predict a clear pharmacokinetics. Here, as a major oligosaccharide component, the tetradecasaccharide (oHG-14) was purified from dHG-5 and its structure was defined as L-Fuc3S4S-α(1,3)-L-Δ4,5GlcA-α(1,3)-{D-GalNAc4S6S-β(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-β(1,3)-}3-D-GalNAc4S6S-β(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ol. oHG-14 showed potent iXase inhibitory activity in vitro and antithrombotic effect in vivo comparable to dHG-5. After single subcutaneous administration of oHG-14 at 8, 14.4 and 32.4 mg/kg to rats, the absolute bioavailability was 71.6 %–80.9 % determined by the validated bioanalytical methods. The maximum concentration (Cmax) was 3.73, 8.07, and 11.95 μg/mL, respectively, and the time reaching Cmax (Tmax) was about 1 h. oHG-14 was mainly excreted by kidney as the parent compound with the elimination kinetics of first-order linear model. Anticoagulant activity of oHG-14 was positively correlated with its concentration in rat plasma. The pharmacokinetics/pharmacodynamics (PK/PD) of oHG-14 is similar to that of dHG-5. This study could provide supportive data for the clinical trial of dHG-5 and further development of pure oligosaccharide as an antithrombotic drug candidate.

Chondroitin sulfate from heads of corb: Recovery, structural analysis and assessment of anticoagulant activity

In this study, glycosaminoglycans (GAGs) were extracted from corb (Sciaena umbra) heads and thoroughly examined for their structure. Through cellulose acetate electrophoresis, the GAGs were identified as chondroitin sulfate (CS), with a recovery yield of 10.35 %. The CS exhibited notable characteristics including a high sulfate content (12.4 %) and an average molecular weight of 38.32 kDa. Further analysis via 1H NMR spectroscopy and SAX-HPLC revealed that the CS primarily consisted of alternating units predominantly composed of monosulfated disaccharides at positions 6 and 4 of GalNAc (52.6 % and 38.8 %, respectively). The ratio of sulfate groups between positions 4 and 6 of GalNAc (4/6 ratio) was approximately 0.74, resulting in an overall charge density of 0.98. Thermal properties of the CS were assessed using techniques such as differential scanning calorimetry and thermogravimetric analysis. Notably, the CS demonstrated concentration-dependent prolongation of activated partial thromboplastin time (aPTT) and thrombin time (TT) while showing no effect on platelet function. At 200 μg/mL, aPTT and TT coagulation times were 1.4 and 3.7 times faster than the control, respectively. These findings suggest that CS derived from corb heads holds promise as an anticoagulant agent for therapy, although further clinical investigations are necessary to validate its efficacy.

Ion-Exchange Resin/Carrageenan-Copper-Based Nanocomposite: Artificial Neural Network, Advanced Thermodynamic Profiling, and Anticoagulant Studies.

Carrageenan (CG) and ion exchange resins (IERs) are better metal chelators. Kappa (κ) CG and IERs were synthesized and subjected to copper ion (Cu2+) adsorption to obtain DMSCH/κ-Cu, DC20H/κ-Cu, and IRP69H/κ-Cu nanocomposites (NCs). The NCs were studied using statistical physics formalism (SPF) at 315-375 K and a multilayer perceptron with five input nodes. The percentage of Cu2+ uptake efficiency was used as an outcome variable. Via the grand canonical ensemble, SPF gives models for both monolayer and multilayer sorption layers. For in vitro anticoagulant activity (ACA), the activated partial thromboplastin time were calculated using 100 μL of rabbit plasma incubated at 37 °C. After 2 min, 100 L of 0.025 M CaCl2 was added, and the clotting time was recorded for each group (n = 6). The results demonstrated that the key covariables for the adsorption process were pH and concentration. The results of artificial neural network models were comparable with the experimental findings. The error rates varied between 4.3 and 1.0%. The prediction analysis results ranged from 43.6 to 89.2. The ΔG and ΔS values for IRP69H/κ-Cu obtained were -18.91 and -16.32 and 26.21 and 22.74 kJ/mol for the temperatures 315 and 345 K, respectively. Adsorbate species were perpendicular to the adsorbent surfaces, notwithstanding the apparent importance of macro- and micropore volumes. These adsorbents typically fluctuate with temperature changes and contain one or more layers of sorption. Negative and positive sorption energies correspond to endothermic and exothermic processes. The biosorption energy (E1 and E2) values in this experiment have a value of less than 23 kJ mol-1. Complex SPF models' energy distributions validate surface properties and interactions with adsorbates. At a concentration of 100 μg/mL, DC20H/κ-Cu2+ exhibited an ACA of only 8 s. These NCs demonstrated better greater ACA with the order DC20H/κ < DMSCH/κ < IRP69H/κ. More research is needed to rule out the chemical processes behind the ACA of CG/IER-Cu NCs.

Biosynthesis, characterization, and anticoagulant properties of copper nanoparticles from red seaweed of Acanthophora sp.

In the last few decades, nanoparticles have found extensive use in a variety of biological applications. Traditional medicine widely uses Acanthophora sp., a marine macroalgae, to cure and prevent diabetes, skin disorders, and blood clotting. The present study aims to investigate whether green-synthesized copper nanoparticles (CuNPs) might work as an anticoagulant. The CuNPs were made using an environmentally friendly method that uses Acanthophora extract. We used UV-vis spectroscopy to assess the surface plasmon resonance of the material, scanning electron microscopy (SEM) to analyze its form, and energy dispersive X-ray (EDX) spectroscopy to identify the material's constituent elements. Furthermore, Fourier-transform infrared (FT-IR) determined the functional groups of the CuNPs. The biosynthesis of CuNPs was confirmed by UV-vis spectroscopy, which showed a surface plasmon resonance peak at 570 nm. The FT-IR analysis showed that certain functional groups are involved in the formation of CuNPs. These groups include OH stretching, C=O stretching, C-H bonding, C-N bonding, and Cu vibration. SEM analysis demonstrated the morphology of CuNPs synthesized, with a size of 0.5μm, while EDS analysis confirmed their purity. The anticoagulant activity of prothrombin time (PT) and activated partial thromboplastin time (aPTT) assays showed that the clotting time got longer depending on the concentration. The CuNPs synthesized from Acanthophora had strong anticoagulant effects at 100 μg/mL, further suggesting that they might be useful as a natural blood thinner. The interesting thing we observed is that the green-synthesized CuNPs made from Acanthophora extract could be used in anticoagulation therapy.

A Review on “The In-vitro Study of Anticoagulant Activity of Different Plant Extract”

The aim of this review is to evaluate the plant extract which show highest anticoagulant activity. There are different plant extract to show the anticoagulant activity. On the basis of this study to know about which plant show maximum anticoagulant activity and which plant has minimum anticoagulant activity. The plants used are naturally obtained. They have other pharmacological properties but some plant have significant anticoagulant activity. The plant used for studied are Myrciaria plinioides, Terminalia bellerica, Gymnema sylvestre, Jatropa gossypiifolia, Allium sativum , Curcuma longa,Rubus ulmifolius, Gymnema sylvestre. Among these plant the Gymnema sylvestre has maximum anticoagulant activity, and the other plant show a significant anticoagulant activity. The prothrombin test, activated prothrombin test , thrombin test, recalcification method were used for the in vitro test of anticoagulant activity. The extract of plant were obtained by various extraction process such as maceration, soxhlet extraction, decoction method etc.

Fangs and foliage: Unearthing the haemotoxic secrets of cannabis-dwelling rattlesnakes

Despite a recent surge in high-throughput venom research that has enabled many species to be studied, some snake venoms remain understudied. The long-tailed rattlesnakes (Crotalus ericsmithi, C. lannomi, and C. stejnegeri) are one group where such research lags, largely owing to the rarity of these snakes and the hazardous areas, ripe with drug (marijuana and opium) production, they inhabit in Mexico. To fill this knowledge gap, we used multiple functional assays to examine the coagulotoxic (including across different plasma types), neurotoxic, and myotoxic activity of the venom of the long-tailed rattlesnakes. All crude venoms were shown to be potently anticoagulant on human plasma, which we discovered was not due to the destruction of fibrinogen, except for C. stejnegeri displaying minor fibrinogen destruction activity. All venoms exhibited anticoagulant activity on rat, avian, and amphibian plasmas, with C. ericsmithi being the most potent. We determined the mechanism of anticoagulant activity by C. ericsmithi and C. lannomi venoms to be phospholipid destruction and inhibition of multiple coagulation factors, leading to a net disruption of the clotting cascade. In the chick biventer assay, C. ericsmithi and C. lannomi did not exhibit neurotoxic activity but displayed potential weak myotoxic activity. BIRMEX® (Faboterápico Polivalente Antiviperino) antivenom was not effective in neutralising this venom effect. Overall, this study provides an in-depth investigation of venom function of understudied long-tailed rattlesnakes and provides a springboard for future venom and ecology research on the group.

In situ densification and heparin immobilization of bacterial cellulose vascular patch for potential vascular applications

Nowadays, developing vascular grafts (e.g., vascular patches and tubular grafts) is challenging. Bacterial cellulose (BC) with 3D fibrous network has been widely investigated for vascular applications. In this work, different from BC vascular patch cultured with the routine culture medium, dopamine (DA)-containing culture medium is employed to in situ synthesize dense BC fibrous structure with significantly increased fiber diameter and density. Simultaneously, BC fibers are modified by DA during in situ synthesis process. Then DA on BC fibers can self-polymerize into polydopamine (PDA) accompanied with the removal of bacteria in NaOH solution, obtaining PDA-modified dense BC (PDBC) vascular patch. Heparin (Hep) is subsequently covalently immobilized on PDBC fibers to form Hep-immobilized PDBC (Hep@PDBC) vascular patch. The obtained results indicate that Hep@PDBC vascular patch exhibits remarkable tensile and burst strength due to its dense fibrous structure. More importantly, compared with BC and PDBC vascular patches, Hep@PDBC vascular patch not only displays reduced platelet adhesion and improved anticoagulation activity, but also promotes the proliferation, adhesion, spreading, and protein expression of human umbilical vein endothelial cells, contributing to the endothelialization process. The combined strategy of in situ densification and Hep immobilization provides a feasible guidance for the construction of BC-based vascular patches.

Layer-by-Layer Construction of Antibacterial and Anticoagulant Blood Contacting Materials.

Vascular transplantation is a common treatment for Cardiovascular disease (CVD). However, the mismatch of mechanical, structural, or microenvironmental properties of materials limits the clinical application. Therefore, the functional construction of artificial vessels or other blood contact materials remains an urgent challenge. In this paper, the composite nanofibers of polycaprolactone (PCL) with dopamine and polyethylenimine (PEI) coating are first prepared, which are further self-assembled by anticoagulant hirudin (rH) and antimicrobial peptide (AMP) of HHC36 through layer-by-layer (LBL) method. The results of FTIR and XPS analysis show that hirudin and AMP are successfully loaded on PEI-PDA/PCL nanofibers and the hydrophilicity is improved. They also show good mechanical properties that the ultimate tensile strength and elongation at break are better than natural blood vessels. The antibacterial results show that the antibacterial effect is still 93% against E. coli on the fifth day because of the stable and continuous release of HHC36 and rH. The performance of anticoagulant activity also exhibited the same results, which APTT is even 9.7s longer in the experimental group than the control group on the fifth day. The novel materials would be effectively solve the formation of thrombosis around artificial blood vessel grafts and the treatment of inflammation.

Antithrombotic Treatment and Clinical Outcomes After Intracerebral Hemorrhage: A Retrospective Cohort Study from the Swedish Stroke Register.

A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH. We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence. There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.

Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors

Potent and selective inhibition of the structurally homologous proteases of coagulation poses challenges for drug development. Hematophagous organisms frequently accomplish this by fashioning peptide inhibitors combining exosite and active site binding motifs. Inspired by this biological strategy, we create several EXACT inhibitors targeting thrombin and factor Xa de novo by linking EXosite-binding aptamers with small molecule ACTive site inhibitors. The aptamer component within the EXACT inhibitor (1) synergizes with and enhances the potency of small-molecule active site inhibitors by many hundred-fold (2) can redirect an active site inhibitor’s selectivity towards a different protease, and (3) enable efficient reversal of inhibition by an antidote that disrupts bivalent binding. One EXACT inhibitor, HD22-7A-DAB, demonstrates extraordinary anticoagulation activity, exhibiting great potential as a potent, rapid onset anticoagulant to support cardiovascular surgeries. Using this generalizable molecular engineering strategy, selective, potent, and rapidly reversible EXACT inhibitors can be created against many enzymes through simple oligonucleotide conjugation for numerous research and therapeutic applications.

Minimally modified human blood coagulation factor X to bypass direct factor Xa inhibitors

BackgroundDirect oral factor (F)Xa inhibitors are widely used as alternatives to conventional vitamin K antagonists in managing venous thromboembolism and nonvalvular atrial fibrillation. Unfortunately, bleeding-related adverse events remain a major concern in clinical practice. In case of bleeding or emergency surgery, rapid-onset reversal agents may be required to counteract the anticoagulant activity. ObjectivesThe ability of FXa variants to bypass the direct oral FXa inhibitors was assessed. MethodsHuman FXa variants were generated through substitution of phenylalanine 174 (F174) for either alanine, isoleucine, or serine. FXa variants were stably expressed in HEK293 cells and purified to homogeneity using ion-exchange chromatography. ResultsF174-substituted human FX variants demonstrated efficacy in restoring thrombin generation in plasma containing direct FXa inhibitors (apixaban, rivaroxaban, edoxaban). Their ability to bypass the anticoagulant effects stems from a significantly reduced sensitivity for the direct FXa inhibitors due to a decrease in binding affinity determined using molecular dynamics simulations and free energy computation. Furthermore, F174 modification resulted in a partial loss of inhibition by tissue factor pathway inhibitor, enhancing the procoagulant effect of F174-substituted FX. Consequently, the F174A- and F174S-substituted FX variants effectively counteracted the effects of 2 widely used anticoagulants, apixaban and rivaroxaban, in plasma of atrial fibrillation and venous thromboembolism patients. ConclusionThese human FX variants have the potential to serve as a rescue reversal strategy to overcome the effect of direct FXa inhibitors in case of life-threatening bleeding events or emergency surgical interventions.

Selective but not pan-CDK inhibition abrogates 5-FU-driven tissue factor upregulation in colon cancer

Thromboembolic events are complications in cancer patients and hypercoagulability has been linked to the tissue factor (TF) pathway, making this an attractive target. Here, we investigated the effects of chemotherapeutics and CDK inhibitors (CDKI) abemaciclib/palbociclib (CDK4/6), THZ-1 (CDK7/12/13), and dinaciclib (CDK1/2/5/9) alone and in combination regimens on TF abundance and coagulation. The human colorectal cancer (CRC) cell line HROC173 was treated with 5-FU or gemcitabine to stimulate TF expression. TF+ cells were sorted, recultured, and re-analyzed. The effect of treatment alone or in combination was assessed by functional assays. Low-dose chemotherapy induced a hypercoagulable state and significantly upregulated TF, even after reculture without treatment. Cells exhibited characteristics of epithelial-mesenchymal transition, including high expression of vimentin and mucin. Dinaciclib and THZ-1 also upregulated TF, while abemaciclib and palbociclib downregulated it. Similar results were observed in coagulation assays. The same anticoagulant activity of abemaciclib was seen after incubation with peripheral immune cells from healthy donors and CRC patients. Abemaciclib reversed 5-FU-induced TF upregulation and prolonged clotting times in second-line treatment. Effects were independent of cytotoxicity, senescence, and p27kip1 induction. TF-antibody blocking experiments confirmed the importance of TF in plasma coagulation, with Factor XII playing a minor role. Short-term abemaciclib counteracts 5-FU-induced hypercoagulation and eventually even prevents thromboembolic events.

A functional RNA-origami as direct thrombin inhibitor with fast-acting and specific single-molecule reversal agents in vivo model

Injectable anticoagulants are widely used in medical procedures to prevent unwanted blood clotting. However, many lack safe, effective reversal agents. Here, we present new data on a previously described RNA origami-based, direct thrombin inhibitor (HEX01). We describe a new, fast-acting, specific, single-molecule reversal agent (antidote) and present in vivo data for the first time, including efficacy, reversibility, preliminary safety, and initial biodistribution studies. HEX01 contains multiple thrombin-binding aptamers appended on an RNA origami. It exhibits excellent anticoagulation activity in vitro and in vivo. The new single-molecule, DNA antidote (HEX02) reverses anticoagulation activity of HEX01 in human plasma within 30 seconds in vitro and functions effectively in a murine liver laceration model. Biodistribution studies of HEX01 in whole mice using ex vivo imaging show accumulated mainly in the liver over 24 hours and with 10-fold lower concentrations in the kidneys. Additionally, we show that the HEX01/HEX02 system is non-cytotoxic to epithelial cell lines and non-hemolytic in vitro. Furthermore, we found no serum cytokine response to HEX01/HEX02 in a murine model. HEX01 and HEX02 represent a safe and effective coagulation control system with a fast-acting, specific reversal agent showing promise for potential drug development.

Sulfated Polysaccharides with Anticoagulant Potential: A Review Focusing on Structure-Activity Relationship and Action Mechanism.

Thromboembolism is the culprit of cardiovascular diseases, leading to the highest global mortality rate. Anticoagulation emerges as the primary approach for managing thrombotic conditions. Notably, sulfated polysaccharides exhibit favorable anticoagulant efficacy with reduced side effects. This review focuses on the structure-anticoagulant activity relationship of sulfated polysaccharides and the underlying action mechanisms. It is concluded that chlorosulfonicacid-pyridine method serves as the preferred technique to synthesize sulfated polysaccharides. The anticoagulant activity of sulfated polysaccharides is linked to the substitution site of sulfate groups, degree of substitution, molecular weight, main side chain structure, and glycosidic bond conformation. Moreover, sulfated polysaccharides exert anticoagulant activity via various pathways, including the inhibition of blood coagulation factors, activation of antithrombin III and heparin cofactor II, antiplatelet aggregation, and promotion of the fibrinolytic system.

Evaluating anthelmintic, anti-platelet, and anti-coagulant activities, and identifying the bioactive phytochemicals of Amaranthus blitum L.

BackgroundHighlighting affordable alternative crops that are rich in bioactive phytoconstituents is essential for advancing nutrition and ensuring food security. Amaranthus blitum L. (AB) stands out as one such crop with a traditional history of being used to treat intestinal disorders, roundworm infections, and hemorrhage. This study aimed to evaluate the anthelmintic and hematologic activities across various extracts of AB and investigate the phytoconstituents responsible for these activities.MethodsIn vitro anthelmintic activity against Trichinella spiralis was evaluated in terms of larval viability reduction. The anti-platelet activities were assessed based on the inhibitory effect against induced platelet aggregation. Further, effects on the extrinsic pathway, the intrinsic pathway, and the ultimate common stage of blood coagulation, were monitored through measuring blood coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT), respectively. The structures of isolated compounds were elucidated by spectroscopic analysis.ResultsInterestingly, a previously undescribed compound (19), N-(cis-p-coumaroyl)-ʟ-tryptophan, was isolated and identified along with 21 known compounds. Significant in vitro larvicidal activities were demonstrated by the investigated AB extracts at 1 mg/mL. Among tested compounds, compound 18 (rutin) displayed the highest larvicidal activity. Moreover, compounds 19 and 20 (N-(trans-p-coumaroyl)-ʟ-tryptophan) induced complete larval death within 48 h. The crude extract exhibited the minimal platelet aggregation of 43.42 ± 11.69%, compared with 76.22 ± 14.34% in the control plasma. Additionally, the crude extract and two compounds 19 and 20 significantly inhibited the extrinsic coagulation pathway.ConclusionsThese findings extend awareness about the nutritional value of AB as a food, with thrombosis-preventing capabilities and introducing a promising source for new anthelmintic and anticoagulant agents.

Utilization and application of bioactive compounds generated from Fish waste and by product as Functional Food Ingredient: A review

The quest for novel functional food ingredients from natural sources is one of the most important discuss in food science and technology. Food industries dispose their valuable waste and some food industries re-process their wastes and used them as functional food ingredients, thereby developed their economy to survive in the neck cutting competition of the market. Enormous volumes of food processing by-products (FPBs) are produced from food manufacturing industries, accounting it as the second-largest quota of food waste generation. Fish known as ‘rich food for poor people,’ supplies good quality of fats, minerals vitamins and proteins to billions of populaces across the globe. However, the fish processing industry on daily basis generates huge wastes leading to the quest for management of these wastes. These wastes which can be referred to as by-products are generated during removal of head; gutting of the fish and during other secondary processing carried out either onboard in fishing vessels or at processing plants on the shores. Over the years there are bids for utilization of fish wastes and by products for production of functional food ingredients using bioactive compounds produced from them. This was aimed at reduction of processing waste, creation of sustainable economic boost, environmental safety while formulating value added functional food which could be of importance to human and animal health or wellbeing. By-products from fish processing such as blood, fleshy chunks of fatty fish, tails, liver from white lean fish, Fish heads, offal, viscera (gut, intestines, etc.), skin and shells have potentials utilization as raw materials for production of value-added functional food ingredients. Bioactive peptides isolated from various fish protein hydrolysates have reported to have several bioactivities such as immunomodulatory, antioxidative antihypertensive, antithrombotic, anticoagulant activities among others Hence from the review, the recovery of bioactive compound and utilization of these by-products are untapped sources for functional ingredients which can be applied in several aspects of food processing for the benefit of manufactures, supply series of nourishments, and consequently advancing the usefulness of the fish waste in consumers’ health and economic benefits of all stakeholders.

Triple Action of Lignosulfonic Acid Sodium: Anti-protease, Antioxidant, and Anti-inflammatory Effects of a Polymeric Heparin Mimetic.

Heparins are sulfated glycosaminoglycans that are used as anticoagulants to treat thrombosis. Heparins exhibit other potential therapeutic effects, such as anti-inflammatory, anti-viral, and anti-malarial effects. However, the strong anticoagulant activity of heparins poses a risk of life-threatening bleeding, limiting their therapeutic use for other diseases beyond thrombosis. To exploit the other effects of heparins and eliminate the bleeding risk, we explored an alternative polymer called lignosulfonic acid sodium (LSAS), which acts as a sulfonated heparin mimetic. LSAS targets factor XIa to exert an anticoagulant effect, and thus, unlike heparins, it is unlikely to cause bleeding. This study investigated the multiple effects of LSAS to identify potential leads for complex pathologies treatment. A series of chromogenic substrate hydrolysis assays were used to evaluate the inhibition of three inflammation-related proteases by LSAS. Its chemical antioxidant activity against the system of ABTS/hydrogen peroxide/metmyoglobin was also determined. Lastly, the effect of LSAS on TNFα-induced activation of the NF-κB pathway in HEK-293 cells was also tested to determine its cellular anti-inflammatory activity. The results showed that LSAS effectively inhibited human neutrophil elastase, cathepsin G, and plasmin, with IC50 values ranging from 0.73 to 212.5 μg/mL. Additionally, LSAS demonstrated a significant chemical antioxidant effect, with an IC50 value of 44.1 μg/mL. Furthermore, at a concentration of approximately 530 μg/mL, LSAS inhibited the TNFα-induced activation of the NF-κB pathway in HEK-293 cells, indicating a substantial anti-inflammatory effect. An essential advantage of LSAS is its high water solubility and virtual non-toxicity, making it a safe and readily available polymer. Based on these findings, LSAS is put forward as a polymeric heparin mimetic with multiple functions, serving as a potential platform for developing novel therapeutics to treat complex pathologies.

Nanopore-regulated in situ polymerization for synthesis of homogeneous heparan sulfate with low dispersity

The biological activities of heparan sulfate (HS) are intimately related to their molecular weights, degree and pattern of sulfation and homogeneity. The existing methods for synthesizing homogeneous sugar chains of low dispersity involve multiple steps and require stepwise isolation and purification processes. Here, we designed a mesoporous metal-organic capsule for the encapsulation of glycosyltransferase and obtained a microreactor capable of enzymatically catalyzing polymerization reactions to prepare homogeneous heparosan of low dispersity, the precursor of HS and heparin. Since the sugar chain extension occurs in the pores of the microreactor, low molecular weight heparosan can be synthesized through space-restricted catalysis. Moreover, the glycosylation co-product, uridine diphosphate (UDP), can be chelated with the exposed metal sites of the metal-organic capsule, which inhibits trans-cleavage to reduce the molecular weight dispersity. This microreactor offers the advantages of efficiency, reusability, and obviates the need for stepwise isolation and purification processes. Using the synthesized heparosan, we further successfully prepared homogeneous 6-O-sulfated HS of low dispersity with a molecular weight of approximately 6 kDa and a polydispersity index (PDI) of 1.032. Notably, the HS generated exhibited minimal anticoagulant activity, and its binding affinity to fibroblast growth factor 1 was comparable to that of low molecular weight heparins.