Antiplatelet Properties Research Articles

The effects of acetylsalicylic acid on performance, carcass traits, breast meat quality and white striping muscle defects in broiler chickens.

This research aims to reduce white striping muscle defects induced by vascular inflammation and hypoxia using the anti-inflammatory, antiplatelet and anti-atherothrombotic properties of acetylsalicylic acid (ASA). To this end, the effects of different doses (0.3, 0.6, 1, 3 and 6 g L-1) of ASA added to drinking water at 24-48 days on growth performance, carcass traits, footpad dermatitis, white striping and breast meat quality parameters were investigated. The results indicate that 0.3, 1, 3 g L-1 and especially 0.6 g L-1 ASA treatment significantly improved growth performance and meat quality parameters. Also, doses of 0.3, 6 g L-1 and especially 0.6 g L-1 of ASA treatment reduced the incidence of white stripe muscle defects. Consequently, 0.6 g L-1 ASA treatment reduced macrophage infiltrations and myodegeneration caused by growth rate. In addition, this dose increased vascular endothelial growth factor and decreased irisin level in breast muscle. The study also shows that high doses of ASA treatment (3 and 6 g L-1) may make footpad dermatitis more common. This may be due to the fact that ASA can cause side effects such as gizzard ulcers and kidney damage in broiler chickens. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Winery By-Products In Vitro and In Vivo Effects on Atherothrombotic Markers: Focus on Platelet-Activating Factor.

Platelet aggregation and inflammation play a crucial role in atherothrombosis. Wine contains micro-constituents of proper quality and quantity that exert cardioprotective actions, partly through inhibiting platelet-activating factor (PAF), a potent inflammatory and thrombotic lipid mediator. However, wine cannot be consumed extensively due to the presence of ethanol. Alternatively, winery by-products are abundant in similar-to-wine micro-constituents that could be used in food fortification and dietary supplements. Also, the vinification process produces millions of tons of by-products worldwide, posing an environmental matter of waste management. Therefore, the purpose of this literature review is to update the existing data concerning the in vitro anti-platelet and anti-inflammatory properties of winery by-product extracts and their possible health effects through controlled clinical trials in humans, specifically focused on their effects on PAF's actions. Data from in vitro studies report that winery by-product compounds are able to inhibit platelet aggregation against several aggregation factors, as well as to downregulate inflammatory markers. Among their actions, extracts or phenolic compounds present in winery by-products inhibit PAF's actions, a potent inflammatory and thrombotic mediator. Similar conclusions have been drawn from human supplementation studies, which suggest that winery by-product extracts may have beneficial biological effects on the cardiovascular system. Evidence from long-term studies shows that consumption may lower total and low density lipoprotein (LDL) cholesterol, improve insulin sensitivity, decrease lipid and protein oxidative damage, enhance antioxidant capacity, and have mild anti-inflammatory action toward reducing cytokine expression and levels. Data from the limited postprandial studies report that the acute consumption of winery by-product extracts improves glycemic response and reduces platelet reactivity to aggregatory stimuli. Although wine extracts and phenolic compounds have been reported to inhibit PAF's actions and reduce the activity of its biosynthetic enzymes, no data exist concerning the influence of winery by-product extracts. In the future, additional long-term randomized controlled trials or postprandial studies are needed to draw definitive conclusions and establish a viable cardioprotective strategy that incorporates the sustainable use of winery by-products.

Amphiphilic poly(methacryloxyethyl sulfobetaine)-block-poly(ε-caprolactone) blended polyvinyl chloride plastics: Study on the Relationship between molecular structure and antibiofouling properties

The blending of amphiphilic copolymers with plastics is an important method for preparing antibiofouling medical plastics. However, enhancing the enrichment of amphiphilic copolymers on the plastic surface, thereby improving the antibiofouling performance of the plastics remain challenging tasks. Herein, we designed and synthesized a series of amphphilic copolymers, denoted as PSB-b-nPCL. These copolymers possess similar chemical compositions but exhibit distinct topological structures. Antibiofouling flexible polyvinyl chloride (PVC) films were prepared by blending PSB-b-nPCL with PVC. These films showed excellent mechanical and thermal properties. X-ray photoelectron spectroscopy, water contact angle and hydration capacity tests demonstrated that PSB-b-nPCL which bearing more PCL blocks were more prone to migrating to the film surface, thereby enhancing the film’s hydrophilicity. Furthermore, anti-protein adsorption, anti-bacterial and anti-platelet adhesion properties of the films were investigated. It was found that topological structure can obviously affect the antibiofouling performance of films. Specifically, films blended with PSB-b-nPCL containing more PCL blocks exhibited superior performance. The optimal blended film achieved a reduction of 96.4% in bovine albumin adsorption, 82% in platelet adhesion, and nearly complete inhibition of bacterial adhesion. We anticipate that the strategy presented in this work will pave a new path for the development of high performance antibiofouling plastics.

Exploring the therapeutic potential: A comprehensive review on the Phytochemistry of Curcuma aromatic

Curcuma aromatic Salisb. (C. aromatica) is commonly known as wild turmeric mentioned as ‘Vanaharidra’ in Ayurveda, belongs to the ‘ginger family’ Zingiberaceae. It is a perennial herb with characteristic aromatic rhizomes used in many traditional systems of medicines in India, China and other Southeast Asian countries. The rhizome of the plant is rich in alkaloids, flavonoids, curcuminoids, tannins and terpenoids which are reported to be the reasons for its various pharmacological properties. The extraction of compounds in different solvents shows that the plant contains curdione, neocurdione, germacrone as its major components. Extensive literature survey showed that the plant has anti- angiogenic, cholerectic and cholagougic, anthelmintic, antimicrobial, wound healing, anticancer, antioxidant, antidiabetic, anti-inflammmatory, analgesic, antitussive, larvicidal, antimelonogenic, anti-nephrotic, antiplatelet, anti-hyperlipidemic, antivenom, and neuroprotective properties. The plant thus proves to be a promising candidate for the development and designing of modern drugs for several diseases. The present study was aimed to review the phytochemical and pharmacological properties of C. aromatic Salisb.

Antithrombotic but not anticoagulant activity of the thrombin-binding RNA aptamer Apta-1.

Pharmacological intervention of thrombosis is challenging, requiring a fined tune balance between beneficial antithrombotic effect versus risk of major bleeding complications. In this investigation, we elucidated the antithrombotic capacity of the novel 90-mer RNA aptamer Apta-1 and its underlying mechanism of action. We utilized three independent in vivo animal models to establish antithrombotic activity and bleeding risk of Apta-1. Several cellular and molecular techniques were utilized to extensively characterize the effects of Apta-1 on primary and secondary haemostasis. Apta-1 significantly reduced thrombus weight in ferric chloride-induced carotid artery thrombosis. A consistent reduction in thrombus weight was also observed in arteriovenous shunt thrombosis in rats, whereas tail bleeding time was unaffected. Cellular and molecular analyses revealed that Apta-1 interacted with thrombin, resulting in significant inhibition of protease-activated receptor (PAR) signalling in platelets. On the other hand, Apta-1 shortened both thrombin generation and thrombin-induced clotting times. Apta-1 targets the heparin-binding motif exosite II on thrombin leading to significant suppression of platelet PAR1 and PAR4 signalling. Intriguingly, Apta-1 produces substantial antithrombotic activity without anticoagulant or general antiplatelet properties. In fact, we found that Apta-1 accelerates the formation of blood clots and thus supports haemostasis without exhibiting typical anticoagulant properties. We suggest that Apta-1 may be a promising future drug candidate for treatment of thrombosis in diseases/conditions where there are significant risks of serious bleeding complications.

Pharmacological Activities of Aesculus hippocastanum and Its Bioactive Constituents in Hemostasis: A Mechanistic Review

Hemostatic disorders are the leading cause of morbidity and even mortality worldwide. Therefore, there is a growing tendency to develop novel, effective, and safer agents for the management of hemostatic diseases. Current hemostatic agents come with several drawbacks, such as unavoidable adverse effects, instability in oral administration, lack of biodegradability, poor safety profile in long-term uses, and high costs. Therefore, herbal remedies with better safety profiles have become a popular alternative therapeutic option for the prevention and treatment of coagulopathies. Aesculus hippocastanum is a commonly found decorative plant with significant medicinal importance. Its various organs contain valuable phytochemicals, and extensive research has demonstrated the effectiveness of A. hippocastanum-based treatments for venous disorders. This review explores the impact of A. hippocastanum on inflammation, oxidative stress, platelet aggregation, and the endothelium of blood vessels. Early studies on the pharmacological properties of A. hippocastanum indicate that it is an exceptional astringent and hemostatic medicinal plant. Its main bioactive compounds, including escin, esculetin, kaempferol, quercetin, and (‒)-epicatechin, not only exhibit vasoconstriction effects but also demonstrate strong anti-inflammatory, antiplatelet, and antioxidant properties. A. hippocastanum exerts these effects by modulating targets such as P-selectin, Nrf2/HO-1, NF-κB, 5HT2A, P2RY1, P2RX1, and cPLA2. Nevertheless, further research is necessary to thoroughly confirm A. hippocastanum’s effectiveness as a hemostatic agent.

Effect of oleocanthal-rich olive oil on postprandial oxidative stress markers of patients with type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is characterized by postprandial dysmetabolism, which has been linked to post-meal redox disturbances. Oleocanthal (OO), one of the most potent bioactive phenols of extra virgin olive oil, has shown redox modulating properties in vitro. However, its acute, in vivo antioxidant properties have never been studied before. Objective: The aim of this study was to investigate the kinetics of five redox markers (Thiobarbituric acid-reactive substances [TBARS] and glutathione peroxidase activity in serum-GPx3 and erythrocytes (GPx1), protein carbonyls in serum) after the consumption different meals. Design: Five different isocaloric meals comprised of white bread and butter (BU) or butter plus ibuprofen (BU-IBU) or olive oil poor in OO or olive oils containing 250 and 500 mg/Kg of oleocanthal (OO250 and OO500, respectively). We hypothesized that OO-rich olive oil will reduce postprandial oxidative stress in T2DM patients compared to other lipid sources. This study involved 10 patients with T2DM and had a cross-over design. Results: The comparison of incremental Area Under Curves (iAUCs) has shown that OO-rich olive oils were able to alleviate the increments of thiobarbituric acid-reactive substances (TBARS) and GPx3 and induce a higher red blood cells (RBCs) GPx1 activity compared to OO (P < 0.05). The effect was dose and redox marker depended. Correlation analysis in the pooled sample demonstrated a positive association between postprandial ex vivo platelet sensitivity to ADP and iAUC TBARS. In conclusion, our study has shown that OO-rich olive oils can favorably modulate lipid peroxidation and RBC GPx activity in T2DM patients when consumed as part of a carbohydrate meal. Discussion: This study demonstrates for the first time that, apart from its anti-inflammatory and antiplatelet properties, OO can also exert acute antioxidant effects. Conclusion: This finding emphasizes the health benefits of extra virgin olive oil, particularly those with a high OO content, for T2DM patients.

Effect of low-dose aspirin intervention on pre-eclampsia prevention in high-risk pregnant women and its impact on postpartum hemorrhage.

Pre-eclampsia, characterized by hypertension and organ dysfunction during pregnancy, poses significant risks to both maternal and fetal health. Aspirin, known for its antiplatelet properties, has been extensively utilized to mitigate pregnancy-related complications. However, the efficacy of low-dose aspirin in managing pre-eclampsia among high-risk pregnant women and its potential impact on postpartum hemorrhage remain contentious topics. A retrospective analysis was conducted on 344 pregnant women diagnosed with high-risk factors for pre-eclampsia. Among them, 152 received intervention with low-dose aspirin, while the rest did not receive it. The incidence of pre-eclampsia, as well as related complications and outcomes associated with bleeding, were compared and evaluated between the two groups. The study findings indicate a significant reduction in the incidence of pre-eclampsia among pregnant women receiving low-dose aspirin intervention, along with a significantly reduced risk of complications. Additionally, there was no significant statistical difference in postpartum hemorrhage between the two groups (p > 0.05). The safety profile of aspirin usage was found to be favorable. Low-dose aspirin demonstrates promising efficacy as an intervention strategy for high-risk preeclamptic women. It does not increase the risk of postpartum hemorrhage and reduces the occurrence of complications associated with preeclampsia. Therefore, low-dose aspirin presents a potential preventive measure against adverse outcomes associated with high-risk pregnancies related to preeclampsia. Further research is necessary to validate and elucidate the optimal dosage and timing of administration for maximal benefits.

Platelet antiaggregant activity of Hypericum perforatum extracts

BackgroundIn addition to its potential use as an antidepressant, different studies have shown that Hypericum perforatum (HP) can have antibacterial, antioxidant, and antiviral properties. Despite this potential, most of the therapeutic bioactivities attributed to HP need further scientific support. In a previous study we found an inhibitory effect of HP in platelet activation markers. So, in the present work we investigate the effect of HP in another aspect of platelet function, platelet aggregation. MethodsFirst, the effect of different concentrations of the total alcoholic extract of HP on platelet aggregation was studied in 9 healthy donors by aggregometry methods using collagen as agonist. After that, to obtain dose-effect curves, 3 experiments were carried out independently in a single individual using collagen, adenosine diphosphate and epinephrine as agonists. ResultsOur results reveal a marked inter-individual variability and a significant dose-dependent decrease of aggregation responses induced by collagen in the presence of HP extracts (mean of minimum inhibition: 8 % at a dose of 0.068 mg es/ml and mean of maximum inhibition: 43 % at a dose of 0.456 mg es/ml). With the results obtained it was possible to obtained a IC50 value of 0.34 mg es/ml. ConclusionsWe can conclude that HP has a dose-dependent inhibitory effect on platelet function (activation and aggregation responses), therefore, our results suggest that HP may be recognized as an herbal medicine with anti-platelet properties.

Base-Catalyzed Reaction of Isatins and (3-Hydroxyprop-1-yn-1-yl)phosphonates as a Tool for the Synthesis of Spiro-1,3-dioxolane Oxindoles with Anticancer and Anti-Platelet Properties.

An approach to the synthesis of phosphoryl substituted spiro-1,3-dioxolane oxindoles was developed from the base-catalyzed reaction of various isatins with (3-hydroxyprop-1-yn-1-yl)phosphonates. It was found that various aryl-substituted and N-functionalized isatins with the formation of appropriate products with high yields and stereoselectivity when using t-BuOLi are able to react. Cytotoxic activity evaluation suggests that the most significant results in relation to the HuTu 80 cell line were shown by N-benzylated spirodioxolanes. 5-Cloro-N-unsubstituted spirooxindoles exhibit antiaggregational activity exceeding the values of acetylsalicylic acid.

The first in-human study to evaluate the antiplatelet properties of the clopidogrel conjugate DT-678 in acute coronary syndrome patients and healthy volunteers.

DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR. A total of 300 consecutive ACS patients naive to P2Y12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared. Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3mg of DT-678. These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy.

Identification of daurisoline metabolites in rats via the UHPLC-Q-exactive orbitrap mass spectrometer

Daurisoline, a bisbenzylisoquinoline alkaloid extracted from the rhizomes of Menispermum dauricum, exhibits diverse biological activities, encompassing antiplatelet, anti-inflammatory, neuroprotective, and antitumor properties. However, previous investigations have not comprehensively elucidated the metabolic profile and pathways of daurisoline in vivo. Using Ultra-High-Performance Liquid Chromatography with Q-Exactive Orbitrap Mass Spectrometry technology, we comprehensively investigated the metabolites of daurisoline in Sprague-Dawley rats, following intragastric administration. Data collection and analysis were enhanced through Full Scan MS/dd-MS2, in conjunction with parallel reaction monitoring, extracted ion chromatography, and diagnostic fragment ions. Sixty-three metabolites were detected and characterized, including sixty-two novel metabolites and coclaurine. This investigation elucidated the cleavage patterns and tissue distribution characteristics of the metabolism of daurisoline. Furthermore, in vivo reactions, including dehydrogenation, hydroxylation, methylation, sulfation and glucuronidation, were thoroughly examined. Investigating the metabolites of daurisoline in rats has deepened our understanding of its metabolism in vivo, aiding in elucidating its metabolic and pharmacological actions. This provides a valuable foundation for further research into its therapeutic efficacy.

Customized Vascular Repair Microenvironment: Poly(lactic acid)-Gelatin Nanofibrous Scaffold Decorated with bFGF and Ag@Fe3O4 Core-Shell Nanowires.

Vascular defects caused by trauma or vascular diseases can significantly impact normal blood circulation, resulting in serious health complications. Vascular grafts have evolved as a popular approach for vascular reconstruction with promising outcomes. However, four of the greatest challenges for successful application of small-diameter vascular grafts are (1) postoperative anti-infection, (2) preventing thrombosis formation, (3) utilizing the inflammatory response to the graft to induce tissue regeneration and repair, and (4) noninvasive monitoring of the scaffold and integration. The present study demonstrated a basic fibroblast growth factor (bFGF) and oleic acid dispersed Ag@Fe3O4 core-shell nanowires (OA-Ag@Fe3O4 CSNWs) codecorated poly(lactic acid) (PLA)/gelatin (Gel) multifunctional electrospun vascular grafts (bAPG). The Ag@Fe3O4 CSNWs have sustained Ag+ release and exceptional photothermal capabilities to effectively suppress bacterial infections both in vitro and in vivo, noninvasive magnetic resonance imaging (MRI) modality to monitor the position of the graft, and antiplatelet adhesion properties to promise long-term patency. The gradually released bFGF from the bAPG scaffold promotes the M2 macrophage polarization and enhances the recruitment of macrophages, endothelial cells (ECs) and fibroblast cells. This significant regulation of diverse cell behavior has been proven to be beneficial to vascular repair and regeneration both in vitro and in vivo. Therefore, this study supplies a method to prepare multifunctional vascular-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for vascular tissue engineering.

(R)-(-)-Xanthorrhizol Inhibits the Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Matrix Metalloproteinases via the NF-κB Signaling Pathway.

(R)-(-)-xanthorrhizol is a bioactive sesquiterpenoid and major chemical constituent of Curcuma zanthorrhiza rhizomes. It was reported to have many pharmacological activities including nephroprotective, hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, antihypertensive, antihyperglycemic, antiplatelet, estrogenic, and antiestrogenic properties. (R)-(-)-xanthorrhizol was also investigated for antiproliferative activity against many cancer cells including breast, lung, liver, ovarian, and colon cancer. It was also revealed to have a potential effect on TNBC cells MDA-MB-231. Considering the previous studies, this study has aimed to investigate the antimigratory and anti-invasive properties, as well as the possible molecular mechanisms, behind these properties. The findings of (R)-(-)-xanthorrhizol on MDA-MB-231 cell migration and invasion demonstrated significant inhibition at three different concentrations in a concentration-dependent manner, which was observed in the scratch, transwell migration, and invasion assays. Further investigation of the molecular mechanism using gelatin zymography revealed that (R)-(-)-xanthorrhizol prevented cell migration and invasion of breast cancer cells through the inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression. Western blot analysis indicated that the inhibition of matrix metalloproteinases is possibly the result of the inhibition of phosphorylation in the NF-κB signaling pathway. These findings corroborate (R)-(-)-xanthorrhizol to proceed for the further studies as a possible future drug candidate for cancer patients.

The Effects of Fisetin and Curcumin on Oxidative Damage Caused by Transition Metals in Neurodegenerative Diseases.

Neurodegenerative diseases pose a significant health challenge for the elderly. The escalating presence of toxic metals and chemicals in the environment is a potential contributor to central nervous system dysfunction and the onset of neurodegenerative conditions. Transition metals play a crucial role in various pathophysiological mechanisms associated with prevalent neurodegenerative diseases such as Alzheimer's and Parkinson's. Given the ubiquitous exposure to metals from diverse sources in everyday life, the workplace, and the environment, most of the population faces regular contact with different forms of these metals. Disturbances in the levels and homeostasis of certain transition metals are closely linked to the manifestation of neurodegenerative disorders. Oxidative damage further exacerbates the progression of neurological consequences. Presently, there exists no curative therapy for individuals afflicted by neurodegenerative diseases, with treatment approaches primarily focusing on alleviating pathological symptoms. Within the realm of biologically active compounds derived from plants, flavonoids and curcuminoids stand out for their extensively documented antioxidant, antiplatelet, and neuroprotective properties. The utilization of these compounds holds the potential to formulate highly effective therapeutic strategies for managing neurodegenerative diseases. This review provides a comprehensive overview of the impact of abnormal metal levels, particularly copper, iron, and zinc, on the initiation and progression of neurodegenerative diseases. Additionally, it aims to elucidate the potential of fisetin and curcumin to inhibit or decelerate the neurodegenerative process.

Potential antiplatelet agents with grape seed – backbone polyphenols: computational studies

The study focused on grape seed-derived polyphenols for their antiplatelet, anti-inflammatory, and fibrinolytic properties through molecular docking and dynamics simulations. Compounds were evaluated for their effects on P2Y12, PTP1B, thromboxane A2, and other targets. Compounds 1 and 6 showed strong inhibitory potential on P2Y12. Compounds 2 and 7, plus epigallocatechin gallate, demonstrated effective inhibition on NF-KB and COX1. The compounds exhibited drug-like properties and potential for new thrombotic disease therapies. The research sheds light on the interactions between polyphenols and target proteins, paving the way for novel antiplatelet strategies.

Overcoming the challenge of potent endogenous interferences in limaprost quantification: An innovative methodology combining differential mobility spectrometry with LC-MS/MS for ultra-high sensitivity, selectivity and significantly enhanced throughput

Limaprost, an orally administered analogue of prostaglandin E1, possesses potent vasodilatory, antiplatelet, and cytoprotective properties. Due to its extremely low therapeutic doses and exceedingly low plasma concentrations, the pharmacokinetic and bioequivalence studies of limaprost necessitate a highly sensitive quantitative method with a sub-pg/mL level of lower limit of quantification. Moreover, the intensity of endogenous interferences can even exceed the maximum concentration level of limaprost in human plasma, presenting further challenge to the quantification of limaprost. As a result, existing methods have not yet met the necessary level of sensitivity, selectivity, and throughput needed for the quantitative analysis of limaprost in pharmacokinetic and bioequivalence investigations. This study presents a new methodology that combines differential mobility spectrometry (DMS) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and utilizes a distinctive strategy to achieve more accurate DMS conditions. This integration yields a method that is currently the most sensitive and features the shortest analytical time, making it the sole technique capable of meeting the requirements for limaprost pharmacokinetic and bioequivalence investigations. This method demonstrates robustness and is successfully employed in a pharmacokinetic investigation of limaprost in human subjects, underscoring that the combination of DMS with LC-MS/MS serves as an efficacious strategy for overcoming the challenges inherent in analyzing biological samples afflicted by multiple interferences.

Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects.

Neurodegeneration, the decline of nerve cells in the brain, is a common feature of neurodegenerative disorders (NDDs). Oxidative stress, a key factor in NDDs such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease can lead to neuronal cell death, mitochondria impairment, excitotoxicity, and Ca2+ stress. Environmental factors compromising stress response lead to cell damage, necessitating novel therapeutics for preventing or treating brain disorders in older individuals and an aging population. Synthetic medications offer symptomatic benefits but can have adverse effects. This research explores the potential of flavonoids derived from plants in treating NDDs. Flavonoids compounds, have been studied for their potential to enter the brain and treat NDDs. These compounds have diverse biological effects and are currently being explored for their potential in the treatment of central nervous system disorders. Flavonoids have various beneficial effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic, and antioxidant properties. Their potential to alleviate symptoms of NDDs is significant.

Kenaf Seed Cysteine Protease (KSCP) Inhibits the Intrinsic Pathway of the Blood Coagulation Cascade and Platelet Aggregation.

Thrombosis is the key event that obstructs the flow of blood throughout the circulatory system, leading to stroke, myocardial infarction and severe cardiovascular complications. Currently, available antithrombotic drugs trigger several life-threatening side effects. Antithrombotic agents from natural sources devoid of adverse effects are grabbing high attention. In our previous study, we reported the antioxidant, anticoagulant and antiplatelet properties of kenaf seed protein extract. Therefore, in the current study, purification and characterization of cysteine protease from kenaf seed protein extract responsible for potential antithrombotic activity was undertaken. Purification of KSCP (Kenaf Seed Cysteine Protease) was carried out using gel permeation and ion exchange column chromatography. The purity of the enzyme was evaluated by SDS PAGE (Sodium Dodecyl-Sulfate Polyacrylamide Gel Electrophoresis). RP-HPLC (Reverse Phase High-Performance Liquid Chromatography), MALDI-TOF (Matrix-Assisted Laser Desorption Ionization Time-Of-Flight) and CD (Circular Dichroism techniques) were employed for its characterization. Proteolytic, fibrinolytic and kinetic study was done using spectroscopy. Plasma recalcification time, Prothrombin Time (PT), Thrombin clotting time (TCT), Activated Partial Thromboplastin Time (APTT), bleeding time and platelet aggregation studies were carried out for antithrombotic activity of KSCP. A single sharp band of KSCP was observed under both reduced and non-reduced conditions, having a molecular mass of 24.1667kDa. KSCP was found to contain 30.3% helix turns and 69.7% random coils without a beta-pleated sheet. KSCP digested casein and fibrin, and its activity was inhibited by iodoacetic acid (IAA). KSCP was optimally active at pH 6.0 at the temperature of 40°C. KSCP exhibited anticoagulant properties by interfering in the intrinsic pathway of the blood coagulation cascade. Furthermore, KSCP dissolved both whole blood and plasma clots and platelet aggregation. KSCP purified from kenaf seed extract showed antithrombotic potential. Hence, it could be a better candidate for the management of thrombotic complications.

Treating ischemic stroke by improving vascular structure and promoting angiogenesis using Taohong Siwu Decoction: An integrative pharmacology strategy

Ethnopharmacological relevanceNeovessels represent a crucial therapeutic target and strategy for repairing ischemic tissue. Taohong Siwu Decoction (THSWD) exhibits potential in promoting angiogenesis to address ischemic stroke (IS). However, its impact on neovessel structure and function, alongside the underlying molecular mechanisms, remains elusive. Aim of the studyOur aim is to investigate the protective effects of THSWD on neovessel structure and function, as well as the associated molecular mechanisms, utilizing an integrative pharmacological approach. Materials and methodsWe initially employed behavioral tests, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Haematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), Laser Doppler flowmetry (LDF), Evans blue staining, and immunofluorescence to evaluate the protective effects of THSWD on neovascular structure and function in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Subsequently, we utilized network pharmacology, metabolomics, and experimental validation to elucidate the underlying molecular mechanisms of THSWD in enhancing neovascular structure and function. ResultIn addition to significantly reducing neurological deficits and cerebral infarct volume, THSWD mitigated pathological damage, blood-brain barrier (BBB) leakage, and cerebral blood flow disruption. Moreover, it preserved neovascular structure and stimulated angiogenesis. THSWD demonstrated potential in ameliorating cerebral microvascular metabolic disturbances including lipoic acid metabolism, fructose and mannose metabolism, purine metabolism, and ether lipid metabolism. Consequently, it exhibited multifaceted therapeutic effects, encompassing anti-inflammatory, antioxidant, energy metabolism modulation, and antiplatelet aggregation properties. ConclusionTHSWD exhibited protective effects on cerebral vascular structure and function and facilitated angiogenesis by rectifying cerebral microvascular metabolic disturbances in MCAO/R rats. Furthermore, integrated pharmacology offers a promising approach for studying the intricate traditional Chinese medicine (TCM) system in IS treatment.