Anticoagulant Potency Research Articles

The anti-angiogenic, anti-inflammatory and anticoagulant potential of a polysaccharide extracted from the brown alga Cystoseira humilis

The present study aimed to evaluate the properties of a sulfated polysaccharide (PSCH) extracted from the brown alga Cystoseira humilis. We analyzed the chemical composition, anti-angiogenesis activities, anticoagulant, and anti-inflammatory effects of the PSCH, using various techniques encompassing UV–visible spectroscopy, fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (X-RD), scanning electron microscopy (SEM), steric exclusion chromatography (SEC) and high-performance liquid chromatography coupled to refractive index detector (HPLC-RID). The study found that PSCH was a sulfated heteropolysaccharide consisting of glucuronic acid, arabinose, galacturonic acid, xylose and fructose, and has a semi-crystalline nature with a molecular weight of about 379.44 kDa. The PSCH contains 41.77 % carbohydrates, 12.33 % proteins, and 4.59 % sulfates. The PSCH fraction has anti-angiogenic potential highlighted through assays on the chorioallantoic membrane, where vascular branching was inhibited by about 41.65 % and 61.38 % at concentrations of 50 and 100 μg/egg, respectively, compared to the untreated group. PSCH displayed an anti-edematous effect in vivo by reducing malondialdehyde and advanced oxidation protein products in paw tissue after five hours of carrageenan injection. When rats were co-treated with PSCH, there was evidence of a significant increase in antioxidant enzyme activity (superoxide dismutase, glutathione peroxidase, and glutathione) in edematous paw tissues compared to untreated rats. Furthermore, PSCH significantly influenced hematological parameters and the rate of anti-inflammatory serum protein fractions compared to the inflamed group. Interestingly, PSCH may exhibit anticoagulant properties by extending activated partial thrombosis time, thrombin time and prothrombin time. The present study has shown that Cystoseira humilis polysaccharides have antioxidant, anti-angiogenic, anti-inflammatory, and anti-coagulant properties, making them suitable for therapeutic purposes.

Assessment of anticoagulant potential of Halocnemum strobilaceum (Pall.) against black rat (Rattus rattus Lin.) from Algeria

BackgroundBlack rats (Rattus rattus; Rodentia: Muridae) cause significant damage to agricultural and human health, and they are considered a reservoir for a variety of diseases. ObjectivesThe current study aimed to evaluate the toxicity of oral anticoagulants derived from Halocnemum strobilaceum (Pall.) M. Bieb. to these dangerous animals. MethodFour selected doses (100, 150, 200 and 300 mg/day/kg of individual weight) and one control were utilized, with 10 repetitions of each dose (5 ♂ and 5 ♀). The extract was powdered on dates as bait. ResultsUPLC-ESI/MS-MS chromatography identified three distinct coumarins (coumaric acid, p-coumaric acid and 4-hydroxycoumarin). The results showed that the fourth dose used caused the highest number of deaths (100 % after three days of treatment). In contrast, after 48 h of therapy, all rats examined showed lethargy, anorexia and unconsciousness, followed by rapid death at 72 h in the treated individuals. The LD50 was recorded at 146.4 mg.kg−1 with a LT50 of 59.37 h. At the end of the experiment, the autopsies of all deceased individuals allowed us to observe the bleeding of their internal organs. The analysis of PT and aPTT demonstrated that the halophyte under investigation possesses anticoagulant activity that increased with the concentration. Histological sections of the liver revealed cellular alteration and significant necrosis. As well, the kidneys had vascular occlusion with an inflammatory filtrate. ConclusionsTo reduce food losses and wastes caused by these pests, H. strobilaceum will be an important plant for use in protecting against invasive rodents, especially in environmental and stored product programs focused at eradicating rodent pests.

Serological Evaluation of the Anti-coagulant Activity of the Classical Siddha Medicine -‘Veera Mezhugu’ in Wistar Albino Rats

In setting the basis for the management of arterial thrombosis, cardiac ischemic changes followed by any severe coronary atherosclerotic changes or any venous thrombosis, there is a conventional use of Acute thrombolytic agents, Anticoagulants with antiplatelet medications in general. These symptoms complex are mentioned as Thamaraga vaayu or Ruththira vaayu or Maaradaippu(Acute coronary syndrome) and Uthirakattu(thromboembolism) in siddha literatures. Veera mezhugu is one of the Siddha formulations chosen from Anuboga vaithiya navaneetham part-4, which is indicated for Uthirakattu and Thamaragavaayu. The drug prepared as per the Siddha literature. The drug has undergone safety studies and the efficacy studies in Wistar albino rats where the serum of the different groups with different doses are compared with the placebo control to evaluate the anti-coagulant potential. Coagulation profile of the three parameters of Activated partial thromboplastin time(APTT), Prothrombin time(PT) and International normalized ratio(INR) are taken for evaluation and had significant difference between the groups[p<0.05].Serological analysis of the Wistar rats shows significant anticoagulant activity in a dose dependent manner.

Studies on in vivo antithrombotic activity of quercetin, a natural flavonoid isolated from a traditional medicinal plant, African eggplant (Solanum indicum)

Ethnopharmacological relevanceEvery year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically. Aim of the studyThis study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract. Materials and methodsBioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC. ResultsQC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 μM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC50 value of 13.2 ± 1.2 μM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB2) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α). ConclusionEffective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis.

Mutual Inhibition of Antithrombin III and SARS-CoV-2 Cellular Attachment to Syndecans: Implications for COVID-19 Treatment and Vaccination.

Antithrombin III (ATIII) is a potent endogenous anticoagulant that binds to heparan sulfate proteoglycans (HSPGs) on endothelial cells' surfaces. Among these HSPGs, syndecans (SDCs) are crucial as transmembrane receptors bridging extracellular ligands with intracellular signaling pathways. Specifically, syndecan-4 (SDC4) has been identified as a key receptor on endothelial cells for transmitting the signaling effects of ATIII. Meanwhile, SDCs have been implicated in facilitating the cellular internalization of SARS-CoV-2. Given the complex interactions between ATIII and SDC4, our study analyzed the impact of ATIII on the virus entry into host cells. While ATIII binds to all SDC isoforms, it shows the strongest affinity for SDC4. SDCs' heparan sulfate chains primarily influence ATIII's SDC attachment, although other parts might also play a role in ATIII's dominant affinity toward SDC4. ATIII significantly reduces SARS-CoV-2's cellular entry into cell lines expressing SDCs, suggesting a competitive inhibition mechanism at the SDC binding sites, particularly SDC4. Conversely, the virus or its spike protein decreases the availability of SDCs on the cell surface, reducing ATIII's cellular attachment and hence contributing to a procoagulant environment characteristic of COVID-19.

Novel magnetic iron oxide-dextran sulphate nanocomposites as potential anticoagulants: Investigating interactions with blood components and assessing cytotoxicity

Examining the critical role of anticoagulants in medical practice, particularly their central function in preventing abnormal blood clotting, is of the utmost importance. However, the study of interactions between blood proteins and alternative anticoagulant nano-surfaces is still understood poorly. In this study, novel approach involving direct functionalisation of magnetic iron oxide nanoparticles (MNPs) as carriers with sulphated dextran (s-dext) is presented, with the aim of evaluating the potential of magnetically-responsive MNPs@s-dext as anticoagulants. The physicochemical characterisation of the synthesised MNPs@s-dext includes crystal structure analysis, morphology study, surface and electrokinetic properties, thermogravimetric analysis and magnetic properties` evaluation, which confirms the successful preparation of the nanocomposite with sulfonate groups. The anticoagulant potential of MNPs@s-dext was investigated using a standardised activated partial thromboplastin time (APTT) test and a modified APTT test with a quartz crystal microbalance with dissipation (QCM-D) which confirmed the anticoagulant effect. Time-resolved solid-liquid interactions between the MNPs@s-dext and model blood proteins bovine serum albumin and fibrinogen were also investigated, to gain insight into their hemocompatibility, and revealed protein-repellence of MNPs@s-dext against blood proteins. The study also addressed comprehensive cytotoxicity studies of prepared nanocomposites, and provided valuable insights into potential applicability of MNPs@s-dext as a promising magnetic anticoagulant in biomedical contexts.

Anticoagulant activity in Australasian elapid snake venoms and neutralisation with antivenom and varespladib

The venoms of Australasian elapid snakes are known to possess coagulant activity, including some with strong procoagulant activity and others with anticoagulant activity, although the latter are less well known. This study investigates the anticoagulant activity of Australasian elapid snake venoms, and whether this activity is neutralised by commercial snake antivenom and varespladib (PLA2 inhibiting agent). Clotting assays were completed for 34 species of Australasian elapids. Antivenom neutralisation assays with tiger snake antivenom (TSAV) were performed on five species to determine if there was cross-neutralisation. Varespladib neutralisation assays were also completed for the same five species. All Pseudechis species venoms had anticoagulant activity, except P. porphyriacus, which was procoagulant. Pseudechis species venoms had similar anticoagulant potency ranging from the most potent P. colletti venom to the least potent P. butleri venom. The three Austrelaps (copperhead) species venoms were the next most potent anticoagulants. Six further snakes, Elapognathus coronatus, Acanthophis pyrrhus, A. antarcticus, Suta suta, Denisonia devisi and D. maculata, had weaker anticoagulant activity, except for D. maculata which had similar anticoagulant activity to Pseudechis species. Tiger Snake Antivenom (1200mU/mL) neutralised the anticoagulant effect of P. australis for concentrations up to 1 mg/mL. TSAV (1200mU/mL) also neutralised P. colletti, D. maculata, A. superbus and A. pyrrhus venoms at their EC50, demonstrating cross neutralisation. Varespladib neutralised the anticoagulant effect of P. australis venom at 5 μM and for venoms of P. colletti, D. maculata, A. superbus and A. pyrrhus. We found anticoagulant activity to be present in six genera of Australasian snakes at low concentrations, which can be completely neutralised by both antivenom and varespladib. Anticoagulant activity in Australian elapid venoms was associated with species possessing high PLA2 activity without procoagulant snake venom serine proteases.

Evaluation of the genus Hypnea phytochemical and pharmacological potential

The red seaweed Hypnea J.V. Lamouroux is a cosmopolitan genus of the family Cystocloniaceae. It has been used in folk medicine, especially in eastern Asian countries. However, little literature highlighted the phytochemical and pharmaceutical values of its different species. In the past centuries, and until now, different Hypnea species have also been widely utilized as a main component in food recipes because they are rich in various bioactive compounds including polysaccharides, particularly ‘κ-carrageenans’, polyphenolics, vitamins, tannins, saponins, terpenoids, alkaloids, sterols, and minerals. Additionally, the aforementioned constituents have been shown to combat different diseases and complications due to their outstanding antioxidant, anti-inflammatory, antibacterial, anti-proliferative, gastroprotective, anticoagulant, enzyme inhibitor, and immunostimulatory potentials. Considering the aforementioned issues, this review aims to provide detailed information about the different phytochemical and pharmacological potentials of species of the genus Hypnea, as well as their mode of action.

Purification and Structural Analyses of Sulfated Polysaccharides from Low-Value Sea Cucumber Stichopus naso and Anticoagulant Activities of Its Oligosaccharides.

Three polysaccharides (SnNG, SnFS and SnFG) were purified from the body wall of Stichopus naso. The physicochemical properties, including monosaccharide composition, molecular weight, sulfate content, and optical rotation, were analyzed, confirming that SnFS and SnFG are sulfated polysaccharides commonly found in sea cucumbers. The highly regular structure {3)-L-Fuc2S-(α1,}n of SnFS was determined via a detailed NMR analysis of its oxidative degradation product. By employing β-elimination depolymerization of SnFG, tri-, penta-, octa-, hendeca-, tetradeca-, and heptadeca-saccharides were obtained from the low-molecular-weight product. Their well-defined structures confirmed that SnFG possessed the backbone of {D-GalNAc4S6S-β(1,4)-D-GlcA}, and each GlcA residue was branched with Fuc2S4S. SnFS and SnFG are both structurally the simplest version of natural fucan sulfate and fucosylated glycosaminoglycan, facilitating the application of low-value sea cucumbers S. naso. Bioactivity assays showed that SnFG and its derived oligosaccharides exhibited potent anticoagulation and intrinsic factor Xase (iXase) inhibition. Moreover, a comparative analysis with the series of oligosaccharides solely branched with Fuc3S4S showed that in oligosaccharides with lower degrees of polymerization, such as octasaccharides, Fuc2S4S led to a greater increase in APTT prolongation and iXase inhibition. As the degree of polymerization increases, the influence from the sulfation pattern diminishes, until it is overshadowed by the effects of molecular weight.

Haematococcus pluvialis polysaccharides improve microbiota-driven gut epithelial and vascular barrier and prevent alcoholic steatohepatitis development

Algal polysaccharides possess many biological activities and health benefits, such as antioxidant, anti-tumor, anti-coagulant, and immunomodulatory potential. Gut microbiota has emerged as one of the major contributor in mediating the health benefits of algal polysaccharides. In this study we showed that Haematococcus pluvialis polysaccharides (HPP) decreased serum transaminase levels and hepatic triglyceride content, alleviated inflammation and oxidative stress in the liver of chronic and binge ethanol diet-fed mice. Furthermore, HPP reduced endotoxemia, improved gut microbiota dysbiosis, inhibited epithelial barrier disruption and gut vascular barrier (GVB) damage in ethanol diet-fed mice. Co-housing vehicle-fed mice with HPP-fed mice alleviated ethanol-induced liver damage and endotoxemia. Moreover, fecal microbiota transplantation from HPP-fed mice into antibiotic-induced microbiota-depleted recipients also alleviated ethanol-induced liver injury and improved gut epithelial and vascular barrier. Our study demonstrated that HPP ameliorated ethanol-induced gut epithelial and vascular barrier dysfunction through alteration of gut microbiota, therefore preventing alcoholic liver damage.

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.

Antiplatelet and Anticoagulant Effects of Two New Phenylpropanoid Sucrose Esters and Other Secondary Metabolites from the Aerial Part of Canna edulis.

This study isolated pure compounds from Canna edulis aerial parts and assessed their antiplatelet and anticoagulant potential. Structural elucidation resulted in the identification of two new compounds: caneduloside A (1) and caneduloside B (2), and eleven known compounds: 6'-acetyl-3,6,2'-tri-p-coumaroyl sucrose (3), 6'-acetyl-3,6,2'-triferuloyl sucrose (4), tiliroside (5), afzelin (6), quercitrin (7), 2-hydroxycinnamaldehyde (8), cinnamic acid (9), 3,4-dimethoxycinnamic acid (10), dehydrovomifoliol (11), 4-hydroxy-3,5-dimethoxybenzaldehyde (12), and (S)-(-)-rosmarinic acid (13). Compounds 3, 4, 6-9, 13 were previously reported for antithrombotic properties. Hence, antithrombotic tests were conducted for 1, 2, 5, 10-12. All tested compounds demonstrated a dose-dependent antiaggregatory effect, and 10 and 12 were the most potent for both ADP and collagen activators. Additionally, 10 and 12 showed anticoagulant effects, with prolonged prothrombin time and activated partial thromboplastin time. The new compound 1 displayed antiplatelet and anticoagulant activity, while 2 mildly inhibited platelet aggregation. C. edulis is a potential source for developing antithrombotic agents.

A Systematic Review: Safety and Efficacy of Anticoagulation therapy for Atrial fibrillation and venous thromboembolism

For the prevention and treatment of thrombosis, anticoagulants continue to be the principal approach. Since direct thrombin inhibitors are usually saved for patients who need intervention or who have complications, unfractionated heparin, low molecular weight heparin, and warfarin have all been thoroughly studied and used.As a result of their improved pharmacodynamic profiles and ease of use, novel oral anticoagulants are predicted to supplant older ones once they emerge from clinical development. Of all the side effects of anticoagulants, bleeding is the most worrying. Anticoagulant pharmacology, dosage, and toxicity are widely used, so clinicians must be well-versed in these areas. Traditionally, heparin was given to patients who needed parenteral anticoagulation, while warfarin was given to patients who needed oral anticoagulation. There has been a push to create newer, more potent anticoagulants because of warfarin's limited therapeutic index and the requirement for regular laboratory monitoring.

Ascorbic acid-mediated selenium nanoparticles as potential antihyperuricemic, antioxidant, anticoagulant, and thrombolytic agents

Abstract Selenium (Se) is an important trace element that is involved in controlling oxidative stress and inflammatory disorders. Gouty arthritis is the inflammation and pain within the joints and tissues caused due to the accumulation of monosodium urate (MSU) crystals. This study aimed to investigate the antigout, antioxidant, anticoagulant, and thrombolytic potential of ascorbic acid-mediated Se nanoparticles (A-SeNPs). Different analytical techniques were used to investigate the formation of A-SeNPs. The antigout potential of the nanoparticles was carried out using MSU crystal dissolution, uric acid (UA) degradation assay, and xanthine oxidase inhibition (XOI). A-SeNPs exhibited excellent antihyperurecemic activity in a concentration-dependent manner. It was observed that at the tested concentration of 20 mg·mL−1, the A-SeNPs demonstrated significant breakage and dissolution of MSU crystals and resulted in UA degradation of 67.76%. Similarly, A-SeNPs resulted in 76% XOI with an excellent IC50 of 140 µg·mL−1. Furthermore, considerable antioxidant activity was noted for the A-SeNPs as evaluated with multiple antioxidant assays. Finally, the NPs were found to have significant anticoagulant and thrombolytic potential. Thus, it was concluded that A-SeNPs have potent antihyperuricemic, antioxidant, anticoagulant, and thrombolytic activities, making them an ideal choice for future biomedical applications.

Inhibitory potential of recombinant and native peanut Bowman-Birk inhibitor against proteases of human blood coagulation pathway

Plant proteinase/protease inhibitors (PIs) have therapeutic potential besides their role in regulating endogenous protease activity in several physiological processes. They exert their function by inhibiting the catalytic activity of specific proteases. The use of PIs for inhibiting coagulation factors and slowing down the blood coagulation process has emerged as a critical intervention point for developing antithrombotic agents. The present study has demonstrated the characterization of bacterially expressed recombinant peanut Bowman-Birk inhibitor (rPnBBI) and evaluation of its anticoagulant potential compared to native PnBBI (isoinhibitors pool) purified from peanuts. The full-length BBI gene was cloned, and rPnBBI (7.53 kDa) expressed in the soluble fraction of Escherichia coli BL21 (DE3) strain was isolated by passing through the trypsin affinity column. The purified rPnBBI with β-sheets as major secondary structural elements exhibited inhibitory activity towards bovine trypsin and chymotrypsin at diverse pH and temperatures. Both, rPnBBI and PnBBI showed anticoagulant effects by prolonging the activated partial thromboplastin time (aPTT) and inhibiting the activity of proteases/factors (plasma kallikrein, FXIIa, FXIa, FIXa, and FXa) involved in the blood coagulation pathway. Besides, rPnBBI and PnBBI showed a similar inhibitory tendency towards FXIIa, FXIa, and FIXa, while rPnBBI exhibited a higher inhibition potential than PnBBI towards FXa. Contrarily, PnBBI showed higher inhibitory potential than rPnBBI on plasma kallikrein. Altogether, the bioactive BBI molecules from the natural food source peanuts showed significant anticoagulant potential, which could be exploited in the prophylaxis of thromboembolic disorders associated with various human diseases.

Resveratrol as an adjuvant prebiotic therapy in the management of pulmonary thromboembolism.

Pulmonary thromboembolism (PTE) presents a grave threat to patient lives, often marked by arterial occlusion in the pulmonary vasculature, frequently stemming from deep vein thrombosis (DVT). While current anticoagulant therapies offer temporary relief, they fall short of addressing the long-term management of PTE. Notably, PTE-associated mortality rates continue to rise annually, positioning it as a crucial concern within the cardiovascular landscape. An intriguing suspect underlying compromised prognoses is the intricate interplay between the gut microbiome and PTE outcomes. The gut-derived metabolite, trimethylamine N-oxide (TMAO), has emerged as a direct contributor to accelerated thrombogenesis, thereby heightening PTE susceptibility. In pursuit of remedies, research has delved into diverse prebiotic and probiotic interventions, with Resveratrol (RSV) emerging as a promising candidate. This paper explores the potential of RSV, a polyphenolic compound, as an adjuvant prebiotic therapy. The proposed therapeutic approach not only augments anticoagulant potency through strategic pharmacokinetic interactions but also introduces a novel avenue for attenuating future PTE incidents through deliberate gut microbiome modulation. RSV's multifaceted attributes extend beyond its role in PTE prevention. Recognized for its anti-inflammatory, antioxidant, and cardioprotective properties, RSV stands as a versatile therapeutic candidate. It exhibits the ability to curtail platelet aggregation, augment warfarin bioavailability, and mitigate pulmonary arterial wall thickening - an ensemble of effects that substantiate its potential as an adjunct prebiotic for PTE patients. This literature review weaves together the latest insights, culminating in a compelling proposition: RSV is an instrumental player in the trajectory of PTE management.

Bioinspired chitosan based functionalization of biomedical implant surfaces for enhanced hemocompatibility, antioxidation and anticoagulation potential: an in silico and in vitro study.

Endowing implanted biomaterials with better hemocompatibility, anticoagulation, antioxidant and antiplatelet adhesion is necessary because of their potential to trigger activation of multiple reactive mechanisms including coagulation cascade and potentially causing serious adverse clinical events like late thrombosis. Active ingredients from natural sources including Foeniculum vulgare, Angelica sinensis, and Cinnamomum verum have the ability to inhibit the coagulation cascade and thrombus formation around biomedical implants. These properties are of interest for the development of a novel drug for biomedical implants to potentially solve the current blood clotting and coagulation problems which lead to stent thrombosis. The objective of this study was to incorporate different anticoagulants from natural sources into a degradable matrix of chitosan with varying concentrations ranging from 5% to 15% and a composite containing all three drugs. The presence of anticoagulant constituents was identified using GC-MS. Subsequently, all the compositions were characterized principally by using Fourier transform infrared spectroscopy and scanning electron microscopy while the drug release profile was determined using UV-spectrometry for a 30 days immersion period. The results indicated an initial burst release which was subsequently followed by the sustained release pattern. Compared to heparin loaded chitosan, DPPH and hemolysis tests revealed better blood compatibility of natural drug loaded films. Moreover, the anticoagulation activity of natural drugs was equivalent to the heparin loaded film; however, through docking, the mechanism of inhibition of the coagulation cascade of the novel drug was found to be through blocking the extrinsic pathway. The study suggested that the proposed drug composite expresses an optimum composition which may be a practicable and appropriate candidate for biomedical implant coatings.

In-Vitro Experimental Study on the Anticoagulant Activity of Rakta Pravarthana Churna

Coagulation disorders disrupt the delicate balance between clot formation and prevention. Various coagulopathies involve abnormal clotting as a manifestation. Rakta Pravarthana Churna (RPC) is an Ayurvedic formulation designed for external application during Rakta Mokshana to address Apravarthana or clotting tendencies. Aims & Objectives: The in-vitro study aims to evaluate its anticoagulant (thrombolytic) activity using blood samples from healthy human volunteers. Materials & Methods: The clot lysis activity of aqueous and alcohol extracts of Rakta Pravarthana churna at two different concentrations (5% & 20%) along with streptokinase as a positive control and distilled water and alcohol as a negative control was carried out. Results: The aqueous extracts showed clot lysis activity whereas alcoholic extracts did not exhibit evidently significant clot lysis. Discussion: In comparison with positive control (streptokinase), aqueous extract of RPC at 5% concentration showed 10.76% more clot lysis activity, aqueous extract of RPC at 20% concentration showed 14.31% more activity. Conclusion: Aqueous extracts of RPC promote clot dissolution, while alcoholic extracts displayed inhibitory effects. These findings show the complexity of Ayurvedic drug interactions with coagulation processes. The study contributes to the understanding of anticoagulation potential of RPC and its scope for potential therapeutic applications.

Polysaccharides from waste Zingiber mioga leaves: Ultrasonic-microwave-assisted extraction, characterization, antioxidant and anticoagulant potentials

Zingiber mioga is a highly economic crop that is used to produce vegetables, spices and herbal pharmaceuticals. Its edible flower bud contributes most to the economic value, but the big leaves were discarded as agricultural waste, which urgently needs to be exploited. In this work, polysaccharides from waste Z. mioga leaves (PWZMLs) were extracted using ultrasonic-microwave-assisted extraction (UMAE). After purification and characterization, the antioxidation and anticoagulation of PWZMLs were evaluated to appraise the potential in cardiovascular protection. Under the liquid–solid ratio of 26: 1 mL/g, after ultrasonication at 495 W for 10 min, followed by microwaving at 490 W for 5 min, the yield of PWZMLs achieved to 6.22 ± 0.14 %, notably higher (P < 0.01) than other methods, and ultrasound contributed more to the yield than microwave. Various analyses confirmed that PWZMLs were negatively charged polysaccharides with galacturonic acid the dominant uronic acid. PWZMLs exerted excellent antioxidant capacity, especially for scavenging 1, 1-diphenyl-2-picrylhydrazyl radical. PWZMLs also elicited promising anticoagulant property, particularly for prolonging activated partial thromboplastin time and lowering fibrinogen, which were almost equivalent to heparin at the same concentration. PWZMLs contained two polysaccharide fractions (199.53 and 275.42 kDa) that could synergistically contribute to the pronounced antioxidant and anticoagulant activities. The PWZMLs extracted with optimized UMAE have great potential in cardiovascular protection.

The anticoagulant potential of Lippia Alba extract in inhibiting SARS-CoV-2 Mpro: Density functional calculation, molecular docking analysis, and molecular dynamics simulations

Lippia Alba, a plant commonly utilized in traditional folk medicine, particularly in Brazil, is renowned for its essential oil possessing anti-inflammatory, antibacterial, anesthetic, and antiviral properties. In this study, we conducted molecular analysis, density function calculations, and molecular dynamics simulations to evaluate 13 novel anticoagulant compounds derived from the chemical composition of Lippia Alba, with potential anti-SARS-CoV-2 activity. Our investigation focused on the SARS-CoV-2-associated protein, PDB ID: 6Y2G. Comparative analysis with the reference drug Calpain Inhibitor II revealed that all compounds exhibited a high binding affinity to the SARS-CoV-2 Mpro protein, ranging from -7,5 to -9,9 kcal/mol. Among them, three compounds (C10, C12, and C13) demonstrated favorable pharmacokinetic properties, complying with Lipinski's rule of five. Additionally, Density Functional Theory (DFT) calculations were performed to determine quantum parameters, and a 100 ns molecular dynamics simulation provided insights into the binding stability of the promising compounds within the target protein pocket. Based on our findings, compound 10 shows potential as an effective drug molecule for inhibiting SARS-CoV-2.