Anti-inflammatory Research Articles

Systematic review and network meta-analysis on the efficacy and safety of parmacotherapy for hand osteoarthritis.

Hand osteoarthritis poses a significant health challenge globally due to its increasing prevalence and the substantial burden on individuals and the society. In current clinical practice, treatment options for hand osteoarthritis encompass a range of approaches, including biological agents, antimetabolic drugs, neuromuscular blockers, anti-inflammatory drugs, hormone medications, pain relievers, new synergistic drugs, and other medications. Despite the diverse array of treatments, determining the optimal regimen remains elusive. This study seeks to conduct a network meta-analysis to assess the effectiveness and safety of various drug intervention measures in the treatment of hand osteoarthritis. The findings aim to provide evidence-based support for the clinical management of hand osteoarthritis. We performed a comprehensive search across PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials was conducted until September 15th, 2022, to identify relevant randomized controlled trials. After meticulous screening and data extraction, the Cochrane Handbook's risk of bias assessment tool was applied to evaluate study quality. Data synthesis was carried out using Stata 15.1 software. 21 studies with data for 3965 patients were meta-analyzed, involving 20 distinct Western medicine agents. GCSB-5, a specific herbal complex that mainly regulate pain in hand osteoarthritis, showed the greatest reduction in pain [WMD = -13.00, 95% CI (-26.69, 0.69)]. CRx-102, s specific medication characterized by its significant effect for relieving joint stiffness symptoms, remarkably mitigated stiffness [WMD = -7.50, 95% CI (-8.90, -6.10)]. Chondroitin sulfate displayed the highest incidence of adverse events [RR = 0.26, 95% CI (0.06, 1.22)]. No substantial variation in functional index for hand osteoarthritis score improvement was identified between distinct agents and placebo. In summary, GCSB-5 and CRx-102 exhibit efficacy in alleviating pain and stiffness in HOA, respectively. However, cautious interpretation of the results is advised. Tailored treatment decisions based on individual contexts are imperative.

Evaluation of Anti-Inflammatory Activity in Methanolic Seed Extracts of International Sorghum bicolor L. Resources

Sorghum is an important cereal with high value as a health food ingredient because it contains various phenolic compounds. Anti-inflammatory activity was assessed using 12 sorghum resources collected from various countries to explore their potential as medicinal resources. The findings revealed that, at extract concentrations of 25 µg/mL and 50 µg/mL, cell survival rates were observed to be between 70 and 80% for most varieties, with the exception of K159081. In the analysis of anti-inflammatory activity, measured by the rate of nitric oxide (NO) production, sorghum varieties K159041 and K159081 exhibited NO production rates of 0.46 ± 0.38% and 2.58 ± 0.20%, respectively, indicating significant anti-inflammatory properties. The investigation into anti-inflammatory effects also included examining the expression of the inducible nitric oxide synthase (iNOS) gene, which is related to the inflammatory response triggered by LPS in macrophages. Varieties K159041, K159048, K159077, K159078, K159081, K159089, and K159096 were analyzed for this purpose. Further, an expression test of the cyclooxygenase 2 (COX-2) gene revealed values less than 0.4 in K159077, K159081, and K159089, suggesting these sorghum lines possess higher anti-inflammatory activity compared to others. Additionally, the expression analysis of tumor necrosis factor alpha (TNF-α), a gene identified as an inflammatory cytokine, showed that the mRNA levels in the lines K159048, K159077, K159078, K159088, K159089, K159093, and K159096 were expressed at lower levels relative to other sorghum resources, categorizing them as having high anti-inflammatory activity. Notably, the K159081 line exhibited the lowest expression level of all genes associated with inflammation, marking it as a valuable medicinal resource with potential development as an anti-inflammatory agent.

RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study

BackgroundThis study was a randomised, double-blind, placebo-controlled study intended to establish the translatability of the RLS-0071 mechanisms of action from animal disease models to humans by inhibiting neutrophil-mediated inflammation at the tissue level and major inflammatory biomarkers. We hypothesized that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose LPS in healthy participants.MethodsParticipants were randomised to one of three arms to receive inhaled LPS followed by three doses of either low-dose (10 mg·kg−1) or high-dose (120 mg·kg−1loading dose followed by 2 doses of 40 mg·kg−1) RLS-0071 IV or placebo (saline) every 8 h (Q8H). Biomarkers evaluating inflammatory responses, with absolute neutrophil counts in induced sputum as the primary endpoint, were collected before and at 6 and 24 h after LPS challenge.ResultsActive treatment with RLS-0071 showed a similar safety profile to participants receiving placebo. RLS-0071 significantly decreased the numbers of neutrophils in sputum at 6 h post LPS by approximately half (p=0.04). Neutrophil effectors myeloperoxidase, neutrophil elastase, and Interleukin-1β in sputum were also significantly decreased at 6 h for RLS-0071 compared with placebo. Several biomarkers showed trends suggesting sustained decreases for RLS-0071versusplacebo at 24 h.Discussion/ConclusionThis clinical trial demonstrated that RLS-0071 was safe and well tolerated and modulated neutrophil-mediated inflammation in humans after inhaled LPS challenge, consistent with results from prior animal model studies.

Overview of acute liver failure in India.

Acute liver failure (ALF) is an infrequent, but serious complication subsequent to severe acute liver injury (sALI) due to various hepatotoxic agents such as hepatotropic virus(es) and drugs such as anti-tubercular medications, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and anti-cancer and anti-epileptic therapy and due to metabolic and autoimmune disease flares. ALF after sALI presents with encephalopathy associated with prolonged international normalized ratio (INR). Mortality in ALF is high and ranges between 50% and 80%. Due to severe liver damage, multiple sequels consequent to hepatic dysfunction result in complications such as hyperammonemia that culminates in encephalopathy associated with cerebral edema; innate immune paralysis resulting in increased frequency of infections and endotoxemia causing decrease in systemic vascular resistance (SVR) and tissue hypoperfusion and damage-associated molecular patterns (DAMPs) released from damaged hepatic parenchyma inducing pro-inflammatory cytokine storm, which may cause other organ dysfunctions. Certain etiologies such as hepatitis E virus and hepatitis A virus-related ALF or paracetamol-ALF (hyper-acute presentation) have better survival than remaining causes. In addition, if etiology-specific treatment (antivirals for ALF related to hepatitis B virus (HBV) or Herpes simplex virus (HSV) or N-acetylcysteine for paracetamol) is available, then the outcome with treatment is better. About half of the patients can be salvaged with medical therapy. All patients need intensive care and organ support to provide time for the liver to regenerate. Various prognostic models to predict high probability of mortality have been described, which should be used to select patient early during the disease for liver transplantation, which is associated with high long-term survival in these sick patients. The Indian National Association for Study of the Liver (INASL) recommends the ALF-Early Dynamic (ALFED) model as a preferred prognostic model in the Indian scenario, where hepatitis viruses are a dominant etiology of ALF and occur on a naïve liver with good regenerative capacity.

ECM-mimetic, NSAIDs loaded thermo-responsive, immunomodulatory hydrogel for rheumatoid arthritis treatment

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy.ResultsThe surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s.ConclusionIn summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.Graphical

Angiotensinergic effect of β-Caryophylene on Lipopolysaccharide- induced systemic inflammation

Renin-Angiotensin System (RAS) is a peptidergic system, canonically known for its role in blood pressure regulation. Furthermore, a non-canonical RAS regulates pathophysiological phenomena, such as inflammation since it consists of two main axes: the pro-inflammatory renin/(pro)renin receptor ((P)RR) axis, and the anti-inflammatory angiotensin-converting enzyme 2 (ACE2)/Angiotensin-(1–7) (Ang-(1–7))/Mas Receptor (MasR) axis. Few phytochemicals have shown to exert angiotensinergic and anti-inflammatory effects through some of these axes; nevertheless, anti-inflammatory drugs, such as phytocannabinoids have not been studied regarding this subject. Among phytocannabinoids, β-Caryophyllene stands out as a dietary phytocannabinoid with antiphlogistic activity that possess a unique sesquiterpenoid structure. Although its cannabinergic effect has been studied, its angiotensinergic effect reminds underexplored. This study aims to explore the angiotensinergic effect of β-Caryophyllene on inflammation and stress at a systemic level. After intranasal Lipopolysaccharide (LPS) installation and oral treatment with β-Caryophyllene, the concentration and activity of key RAS elements in the serum, such as Renin, ACE2 and Ang-(1–7), along with the stress hormone corticosterone and pro/anti-inflammatory cytokines, were measured in mice serum. The results show that β-Caryophyllene treatment modified RAS levels by increasing Renin and Ang-(1–7), alongside the reduction of pro-inflammatory cytokines and corticosterone levels. These results indicate that β-Caryophyllene exhibits angiotensinergic activity in favor of anti-inflammation.

Characterization, In Silico Antimalarial, Antiinflammatory, Antioxidant, and ADMET Assessment of Neonauclea excelsa Merr.

In our study, we identified the phytoconstituents and carried out antimalarial, anti-inflammatory, antioxidant, and ADMET assessments of Neonauclea excelsa. The phytochemicals were detected and quantified followed by identification via GC-MS. The antimalaria, anti-inflammatory, and antioxidant assessments were done by molecular docking (MD) and molecular dynamics simulation (MDS) while ADMET by ADMET predictions. Saponins (27.33% ±1.20) and terpenes (8.33% ±0.73) were detected while alkaloids, steroids, glycosides, and flavonoids were absent. Exactly 29 compounds were identified with squalene being the most abundant (32.41%). Compound II exhibited the lowest BA (-6.4 kcal/mol) and Ki (20.12 µM), interacting with dihydrofolate reductase-thymidylate synthase. IV exhibited the lowest respective BA and Ki interacting with Plasmodium falciparum hexose transporter protein 1 (-6.2 kcal/mol and 28.20 µM), cyclo-oxygenase-2 (-7.2 kcal/mol and 5.21 µM), and myeloperoxidase (-7.4 kcal/mol and 3.71 µM). Compound VII had the lowest respective BA and Ki interacting with inducible nitric oxide synthase (-8.0 kcal/mol and 1.35 µM), xanthine oxidase (-7.2 kcal/mol and 5.21 µM), and cytochrome p450 21A2 (-7.0 kcal/mol and 7.30 µM). The MDS showed various cluster mobilities and residue fluctuations up to 5.26, 2.96, 5.10, 3.51, 5.02, 4.65, and 6.18 Å for dihydrofolate reductase-thymidylate synthase, Plasmodium falciparum hexose transporter protein 1, inducible nitric oxide synthase (INOS), cyclo-oxygenase-2 (COX2), xanthine oxidase (XO), cytochrome p450 21A2, and myeloperoxidase, respectively. Additionally, these compounds demonstrated good pharmacological properties with minimal toxicity. Conclusively, the identified compounds might be significant contributors to the antimalarial, anti-inflammatory, and antioxidant activity of N. excelsa and are good sources of novel antimalarial, anti-inflammatory, and antioxidant drugs.

Caffeine and Purine Derivatives: A Comprehensive Review on The Chemistry, Biosynthetic Pathways, Synthesis-Related Reactions, Biomedical Prospectives and Clinical Applications.

Caffeine and purine derivatives represent interesting chemical moieties, which show various biological activities. Caffeine is an alkaloid that belongs to the family of methylxanthine alkaloids and it is present in food, beverages, and drugs. Coffee, tea, and some other beverages are a major source of caffeine in the human diet. Caffeine can be extracted from tea or coffee using hot water with dichloromethane or chloroform and the leftover is known as decaffeinated coffee or tea. Caffeine and its derivatives were synthesized via different procedures on small and large scales. It competitively antagonizes the adenosine receptors (ARs), which are G protein-coupled receptors largely distributed in the human body, including the heart, vessels, brain, and kidneys. Recently, many reports showed the effect of caffeine derivatives in the treatment of many diseases such as Alzheimer's, asthma, parkinsonism, and cancer. Also, it is used as an antioxidant, anti-inflammatory, analgesic, and hypocholesterolemic agent. The present review article discusses the synthesis, reactivity, and biological and pharmacological properties of caffeine and its derivatives. The biosynthesis and biotransformation of caffeine in coffee and tea leaves and the human body were summarized in the review.

Role of ionic liquids in ibuprofen-based eutectic systems: Aqueous solubility, permeability, human cytotoxicity, hemolytic activity and anti-inflammatory activity

Eutectic systems, as well as ionic liquids (ILs), offer a potential solution to the challenges associated with low solubility, polymorphism, and limited bioavailability of active pharmaceutical ingredients (APIs). Herein, we prepared twelve pharmaceutically active eutectics based on ibuprofen (Ibu), a widely accessible without prescription non-steroidal anti-inflammatory drug (NSAID), and imidazolium-based ILs ([C2C1Im]Cl, [C2(OH)C1Im]Cl and [C2C1Im][C1CO2]) and cholinium salt ([N1112(OH)]Cl) at different molar ratio (2:1, 1:1, 1:2 and 1:5). All eutectic systems were characterized by DSC and NMR, and their polarity was assessed using the Kamlet-Taft approach to characterize the non-specific (polarity/polarizability) and specific (hydrogen bonding ability) interactions. An upgrade of the aqueous solubility (water and biological simulated fluids) for the Ibu-based eutectics relatively to ibuprofen was verified. Also, the assessment of ionicity (viscosity, conductivity, and density) was attained, confirming the formation of ion-pairs or clusters, that increase the potential of these liquids to be more membrane diffusive. The biocompatibility of the Ibu-based eutectics was evaluated up to 3 mM (well above the ibuprofen maximum plasma concentration) through a hemolytic activity assay and in vitro cytotoxicity as-says with two human cell lines (Caco-2 colon carcinoma cells and HepG2 hepatocellular carcinoma cells), without impairing their hemolytic and cytotoxic response. Additionally, the anti-inflammatory activity was evaluated by the inhibition of bovine serum albumin (BSA) denaturation and inhibition of cyclooxygenases (COX-1 and COX-2) enzymes, showing that the ibuprofen eutectic formulations maintain the anti-inflammatory response of ibuprofen with the opportunity to improve the selectivity towards COX-2, allowing the development of safer NSAIDs.

Antioxidant and anti-inflammatory function of Eupatorium adenophora Spreng leaves (EASL) on human intestinal Caco-2 cells treated with tert-butyl hydroperoxide

Chronic non-communicable diseases (CNCDs) pose a significant public health challenge. Addressing this issue, there has been a notable breakthrough in the prevention and mitigation of NCDs through the use of antioxidants and anti-inflammatory agents. In this study, we aim to explore the effectiveness of Eupatorium adenophora Spreng leaves (EASL) as an antioxidant and anti-inflammatory agent, and its potential applications. To construct a cellular model of oxidative damage and inflammation, Caco-2 cells were treated with tert-butyl hydroperoxide (t-BHP). The biocompatibility of EASL-AE with Caco-2 cells was assessed using the MTT assay, while compatibility was further verified by measuring LDH release and the protective effect against oxidative damage was also assessed using the MTT assay. Additionally, we measured intracellular oxidative stress indicators such as ROS and 8-OHdG, as well as inflammatory pathway signalling protein NFκB and inflammatory factors TNF-α and IL-1β using ELISA, to evaluate the antioxidant and anti-inflammatory capacity of EASL-AE. The scavenging capacity of EASL-AE against free radicals was determined through the DPPH Assay and ABTS Assay. Furthermore, we measured the total phenolic, total flavonoid, and total polysaccharide contents using common chemical methods. The chemical composition of EASL-AE was analyzed using the LC–MS/MS technique. Our findings demonstrate that EASL-AE is biocompatible with Caco-2 cells and non-toxic at experimental levels. Moreover, EASL-AE exhibits a significant protective effect on Caco-2 cells subjected to oxidative damage. The antioxidant effect of EASL-AE involves the scavenging of intracellular ROS, while its anti-inflammatory effect is achieved by down-regulation of the NFκB pathway. Which in turn reduces the release of inflammatory factors TNF-α and IL-1β. Through LC–MS/MS analysis, we identified 222 compounds in EASL-AE, among which gentianic acid, procaine and L-tyrosine were the compounds with high antioxidant capacity and may be the effective constituent for EASL-AE with antioxidant activity. These results suggest that EASL-AE is a natural and high-quality antioxidant and anti-inflammatory biomaterial that warrants further investigation. It holds great potential for applications in healthcare and other related fields.

Neuroprotective effects of Si-based hydrogen-producing agent on 6-hydroxydopamine-induced neurotoxicity in juvenile mouse model

Neurotoxins have been extensively investigated, particularly in the field of neuroscience. They induce toxic damage, oxidative stress, and inflammation on neurons, triggering neuronal dysfunction and neurodegenerative diseases. Here we demonstrate the neuroprotective effect of a silicon (Si)-based hydrogen-producing agent (Si-based agent) in a juvenile neurotoxic mouse model induced by 6-hydroxydopamine (6-OHDA). The Si-based agent produces hydrogen in bowels and functions as an antioxidant and anti-inflammatory agent. However, the effects of the Si-based agent on neural degeneration in areas other than the lesion and behavioral alterations caused by it are largely unknown. Moreover, the neuroprotective effects of Si-based agent in the context of lactation and use during infancy have not been explored in prior studies. In this study, we show the neuroprotective effect of the Si-based agent on 6-OHDA during lactation period and infancy using the mouse model. The Si-based agent safeguards against the degradation and neuronal cell death of dopaminergic neurons and loss of dopaminergic fibers in the striatum (STR) and ventral tegmental area (VTA) caused by 6-OHDA. Furthermore, the Si-based agent exhibits a neuroprotective effect on the length of axon initial segment (AIS) in the layer 2/3 (L2/3) neurons of the medial prefrontal cortex (mPFC). As a result, the Si-based agent mitigates hyperactive behavior in a juvenile neurotoxic mouse model induced by 6-OHDA. These results suggest that the Si-based agent serves as an effective neuroprotectant and antioxidant against neurotoxic effects in the brain, offering the possibility of the Si-based agent as a neuroprotectant for nervous system diseases.

Carbon-in-carbon: Hybrid carbonized nanomaterials with multifunctional activities for the treatment of endophthalmitis

Infectious endophthalmitis (EO) is a severe eye condition characterized by inflammation of the eye’s internal fluids and tissues, often resulting from infection by bacteria or fungi. Patients with EO typically experience reduced vision, pain, and conjunctival infection. Despite the use of antibiotics, challenges such as inflammation and drug resistance remain. In this work, we have developed dextran/aliphatic diamines carbonized nanogels (DEX/ADA-CNGs) as board-spectrum antimicrobial agents by a one-step mild carbonization procedure. The CNGs exhibit not only antimicrobial properties but also show good drug delivery potential. Curcumin-based carbon quantum dots (Cur-CQDs) as an anti-inflammatory agent are loaded into DEX/ADA-CNGs to form hybrid carbon-in-carbon nanocomposites (Cur-CQDs@DEX/ADA-CNGs), showing combined antimicrobial, antioxidative, and anti-inflammatory activities. Impressively, CQDs@DEX/ADA-CNGs maintain strong antibacterial effectiveness against drug-resistant strains, with minimum inhibitory concentrations below 110 µg mL−1. The Cur-CQDs@DEX/ADA-CNGs have demonstrated high biocompatibility both in vitro and in vivo. In a rat model of EO, they rapidly (less than 5 days) reduce microbial infection and inflammation in the eye. Given these promising results, Cur-CQDs@DEX/ADA-CNGs show great potential as an enduring intravitreal treatment option for infectious EO.

Inverse association of the systemic immune-inflammation index with serum anti-ageing protein Klotho levels in individuals with osteoarthritis: A cross-sectional study.

The association between the systemic immune-inflammation index (SII) and the serum soluble-Klotho concentration (pg/ml) in osteoarthritis (OA) patients is unknown. This study aimed to investigate the relationship between the SII and serum soluble-Klotho levels in OA patients. All study data were obtained from the National Health and Nutrition Examination Survey (NHANES) database (n = 1852 OA patients; age range = 40-79 years). The SII and serum Klotho measurement data are from the NHANES mobile examination centre. The SII values were divided into quartiles (Q1-4: 0.02-3.36, 3.36-4.78, 4.79-6.70, and 6.70-41.75). A multivariate linear regression model was constructed to evaluate the association between the SII and serum Klotho levels in OA patients; interaction tests were conducted to test the stability of the statistical results. Multivariate linear regression revealed a negative linear relationship between the SII and serum Klotho concentration in OA patients (β = -6.05; 95% CI: -9.72, -2.39). Compared to Q1, Q4 was associated with lower serum Klotho concentrations (β = -59.93; 95% CI: -96.57, -23.28). Compared with that of Q1, the β value of Q2-Q4 showed a downwards trend as the SII increased (Ptrend <0.001). The stratified analysis results indicated that the SII had a greater sensitivity in predicting serum Klotho concentrations in OA patients aged 60-79 years (Pinteraction = 0.028). There was a significant negative linear correlation between the SII and serum Klotho concentration in OA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in OA patients. Klotho may be a potential anti-inflammatory drug for OA treatment.

QUANTITATIVE DETERMINATION OF SOME NON-STEROIDAL ANTI-INFLAMMATORY DRUGSAND THEIR ACID DISSOCIATION CONSTANTS BY DIRECT POTENTIOMETRY

Objective: A potentiometric titration method was applied to determine non-steroidal anti-inflammatory drugs. The quantitative analysis and the treatment of the primary data are based on a nonlinear regression procedure using commercial software. A general formula valid for every type of acid-base titration, derived before is used as a direct input. Methods: Potentiometric titration of ibuprofen, flurbiprofen, and ketoprofen with sodium hydroxide solution (0.1 mol/l). The solutions of ibuprofen, flurbiprofen, and ketoprofen were prepared in solvent CH3OH: H2O (40:60%). The determination was carried out using a 713 Metrohm pH meter, equipped with Metrohm combined electrode ref. 6.0228.000 Pt1000 with temperature sensor and auto burette. The analysis was performed at ionic strength (I=0.2 mol/l KCl) and t = 25±0.2 °C. Results: The discussed substances were analyzed using potentiometric titration with a standard sodium hydroxide solution (0.1 mol/l). The experimental data V, ml/E, mV and the conditions of these titrations were used as input in the Data Fit program fixing the following parameters Vo =100.0 ml; Ct (NaOH) = 0.1000 mol/l; S = 59.16 mV (corresponding to 25 °C theoretical value) and Kw = 1.2 10-14 (ionic strength 0.2 mol/l). The analytical results for ibuprofen, flurbiprofen and ketoprofen were determined with good accuracy (error+0.4 % foribuprofen+0.2 % for flurbiprofen and+0.2 % for ketoprofen) and precision (1 % for the three). The quantity and acid-base constants of ibuprofen, flurbiprofen, and ketoprofen were determined alone and in tablets. The validation of the method showed very good accuracy and precision. Conclusion: The present approach can be successfully used in routine analysis of the study drugs in quality control laboratories.

Detection and management of clinically relevant drug-drug interactions with direct oral anticoagulants: an intervention study in community pharmacies

IntroductionDirect oral anticoagulants (DOACs) are increasingly used and can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Skilled drug interaction management is essential to ensure safe and effective use of DOACs. In this study, we aimed to investigate the impact of the detection and management of DDIs with DOACs in a real-life community pharmacy setting on the pharmacotherapy of DOAC users. MethodsWe conducted an intervention study in 201 community pharmacies in Belgium. On random days, patients purchasing DOACs or drugs known to interact with them were screened. When a DDI with the DOAC was detected, the pharmacist contacted the prescribing physician to discuss the management of the interaction. A previously developed practice-oriented DDI list accompanied by management plans for ambulatory care was used for both screening and management of the DDIs. ResultsIn total, 751 patients were included, among whom 875 DDIs were identified, primarily pharmacodynamic DDIs (95.7 %). Predominant interacting drug classes included selective serotonin or serotonin and norepinephrine reuptake inhibitors (32.9 %), antiplatelets (30.9 %), and non-steroidal anti-inflammatory drugs (28.9 %). In 43.0 % of DDIs, an intervention was decided upon. At three-month follow-up, proposed pharmacotherapy changes had been implemented in 79.1 % of these DDIs. ConclusionsThis study demonstrates that active screening and management of DDIs with DOACs in community pharmacies, in close collaboration with prescribing physicians, resulted in changes in pharmacotherapy in a substantial number of patients. This may contribute significantly to the safer utilisation of DOACs in high-risk populations.

The Formulation, Development And Evaluation Of Ointment For Anti-Inflammatory Activity

The search for safer anti-inflammatory agents has led to exploration of natural sources such as curcumin and fenugreek. Curcumin, derived from Curcuma longa, and α-linolenic acid from Trigonella foenum-graecum, exhibit significant anti-inflammatory properties. This study focuses on formulating an ointment utilizing these extracts for topical application. Molecular docking techniques were employed to assess the binding affinities of curcumin and α-linolenic acid. The ointment was prepared using various bases and preservatives, and its physicochemical properties were evaluated. Stability studies revealed consistent properties under different temperature conditions. Characterization of the drug extracts and ointment formulations was conducted to ensure efficacy and safety. The ointment showed promising results in terms of stability and efficacy, particularly formulation F2, suggesting its potential as a topical anti-inflammatory therapy with improved patient compliance

Exploring the anti-inflammatory potential of the polyphenolic compounds in Moringa oleifera leaf: in silico molecular docking

ABSTRACT A recent study conducted an in silico model to investigate the potential of Moringa oleifera’s ethanolic leaf extract as a natural anti-inflammatory agent. The HPLC analysis identified 7 phenolic acids (benzoic acid 28%, syringic acid 23%, ellagic acid 19%, chlorogenic acid 12%, catechol 11%, gallic acid 5%, and caffeic acid 2%) and 5 flavonoids (naringenin 31%, kaempferol 30%, apigenin 14%, rutin 13%, and quercetin 12%) that are known to have anti-inflammatory activities in vitro tested on human interleukin-1β (IL-1β) and interleukin-6 (IL-6) in a previously prepared study (Hamdy, 2023) The Moringa polyphenol compounds were docked against IL-1β, IL-6, and the human interleukin-1 receptor (IL1RA) using Auto-Dock Vina. Caffeic acid, chlorogenic acid, and kaempferol interacted with amino acid residues in IL-1β by creating hydrogen bonds and hydrophobic interactions. The co-crystalized ligand attached to IL-1β displayed an affinity score of −8.96 kcal/mol. Caffeic acid, chlorogenic acid, quercetin, rutin, and syringic acid had unique interaction patterns with IL-6, forming hydrogen bonds and being hydrophobic. The interactions’ binding energies ranged from −5.97 to 5.26 kcal/mol. Moringa’s polyphenolic compounds also docked with IL1RA, where rutin and chlorogenic acid exhibited binding energies of −8.96 kcal/mol and −7.12 kcal/mol, respectively, and created hydrophobic interactions and hydrogen bonds. In conclusion, Moringa oleifera polyphenols can interact with IL-1β, IL-6, and IL-1RA to reduce inflammation, making it a potential treatment strategy for improving recovery.

Preparation of β-cyclodextrin derivatives/metamizole inclusion complex nanofibers: Characterization, drug release, and wound scratch assay

Nanofibrous wound dressings fabricated by electrospinning have attracted significant research interest as they enable the controlled release of active substances at the wound site. The development of electrospun nanofibers with anti-inflammatory drugs, which demonstrate great potential for wound healing applications, is one of the main focuses of present research efforts. In this study, nanofibrous webs of 2-hydroxypropyl-β-cyclodextrin (HPβCD) and methyl-β-cyclodextrin (MβCD) loaded with metamizole (MMS) were fabricated by electrospinning. The prepared nanofibers were characterized by field-emission scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, thermogravimetric/differential thermal analysis, 1H nuclear magnetic resonance spectroscopy, ultraviolet diffuse reflectance spectroscopy, and photoluminescence analysis. The interactions of HPβCD and MβCD with MMS in aqueous solutions were studied using absorption and fluorescence spectroscopy, and the 1:1 MMS/CD inclusion complexes were theoretically analyzed at the PM3 level of theory. Furthermore, the drug release, biocompatibility, and wound scratch assay of the nanofibers were evaluated. In vitro drug release analysis revealed controllable release of MMS from the nanofibers. The CD nanofibers loaded with MMS showed good biocompatibility with skin fibroblasts. An in vitro wound scratch assay indicated that the nanofibers promoted fast wound closure with a rate of 98.66 ± 3.9%. In summary, the prepared nanofibrous webs are promising candidates for wound-dressing applications.

Exploring the Role of Apigenin in Neuroinflammation: Insights and Implications.

Neuroinflammation, a hallmark of various central nervous system disorders, is often associated with oxidative stress and neuronal or oligodendrocyte cell death. It is therefore very interesting to target neuroinflammation pharmacologically. One therapeutic option is the use of nutraceuticals, particularly apigenin. Apigenin is present in plants: vegetables (parsley, celery, onions), fruits (oranges), herbs (chamomile, thyme, oregano, basil), and some beverages (tea, beer, and wine). This review explores the potential of apigenin as an anti-inflammatory agent across diverse neurological conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease), cancer, cardiovascular diseases, cognitive and memory disorders, and toxicity related to trace metals and other chemicals. Drawing upon major studies, we summarize apigenin's multifaceted effects and underlying mechanisms in neuroinflammation. Our review underscores apigenin's therapeutic promise and calls for further investigation into its clinical applications.

Development of novel nitric oxide production inhibitors based on the 7H-pyrrolo[2,3-d]pyrimidine scaffold.

Nitric oxide (NO), the smallest signaling molecule known, can be excessively produced by overexpressed inducible nitric oxide synthase (iNOS), and eventually leads to multiple inflammatory related diseases. Thus, reducing the overexpression of NO represents as very potential anti-inflammatory strategy. In current study, a series of compounds were designed and synthesized based on the hybridization of 7H-pyrrolo[2,3-d]pyrimidine and cinnamamide fragments in order to develop novel NO production inhibitors. Among them, compound S2h displayed a vigorous inhibitory activity on NO production with an IC50 value of 3.21 ± 0.67 µM, which was much lower than that of the positive control Nω-nitro-L-arginine (L-NNA, IC50 = 28.36 ± 3.13 µM). Due to its obeying Lipinski's and Veber's rules that guarantee compounds with good oral bioavailability, S2h effectively suppressed the paw swelling in carrageenan-induced mice. Additionally, compound S2h formed clear interactions with iNOS protein according to the docking analysis. Therefore, compounds S2h is a promising lead compound for further development of potent iNOS inhibitors or anti-inflammatory agents.