Search Results (1,414)

Background: Osteoarthritis (OA) is a prevalent degenerative joint disease often causing functional disability. Current therapies provide only temporary relief and can cause adverse effects that frequently result in pain and disability. Current pharmacological options offer only temporary symptom relief and may cause adverse effects. Piper sarmentosum (PS), a plant traditionally used for its medicinal properties, has demonstrated antioxidant and anti-inflammatory activities that may counteract OA-related degeneration. This study provides preliminary insight into the therapeutic potential of PS aqueous extract in human OA chondrocytes. Methods: Compounds in the PS aqueous extract were profiled using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Primary human OA chondrocytes (HOCs) were treated with 0.5, 2, and 4 µg/mL of PS aqueous extract for 72 h. Key OA-related parameters were assessed, including anabolic markers (sulfated glycosaminoglycan (sGAG), collagen type II (COL II), aggrecan core protein (ACP), SRY-box transcription factor 9 (SOX9)), catabolic markers (matrix metalloproteinase (MMP) 1, MMP13, cyclooxygenase 2 (COX2)), oxidative stress (nitric oxide (NO) production, inducible NO synthase (iNOS) expression), and inflammatory responses (interleukin (IL) 6). Gene expression was quantified using qPCR, and protein levels were evaluated using the colorimetric method, immunocytochemistry, and Western blot. Results: A total of 101 compounds were identified in the extract, including vitexin, pterostilbene, and glutathione—bioactives known for antioxidant, anti-inflammatory, and chondroprotective functions. PS-treated chondrocytes maintain healthy polygonal morphology. PS aqueous extract significantly enhanced anabolic gene expression (COL2A1, ACP, SOX9) and sGAG production, while concurrently suppressing COX2 expression and NO synthesis. Additionally, PS aqueous extract reduced COX2 and iNOS protein levels, indicating inhibition of the NO signaling pathway. Catabolic activity was attenuated, and inflammatory responses were partially reduced. Conclusions: PS aqueous extract exhibits promising chondroprotective, antioxidant, and anti-inflammatory effects in human OA chondrocytes, largely through the suppression of NO-mediated catabolic signaling. The presence of multiple bioactive compounds supports its mechanistic potential. These findings highlight PS aqueous extract as a potential therapeutic candidate for OA management. Further ex vivo and in vivo studies are warranted to validate its efficacy and clarify its mechanism in joint-tissue environments. Full article

Chronic sleep deprivation (CSD) disrupts redox homeostasis and enhances neuroinflammatory activation, contributing to progressive cognitive impairment. Propyl gallate (PG), a lipophilic ester of gallic acid with established antioxidant activity, has not been investigated in the context of prolonged sleep deprivation. The current study examined whether PG alleviates CSD-induced oxidative imbalance, inflammatory activation, and associated behavioral deficits. Male ICR mice were subjected to 14 days of CSD using a rolling-drum apparatus and received oral PG (50, 100, or 200 mg/kg) or Ginkgo biloba extract (GBE, 40 mg/kg). Behavioral outcomes were assessed through a battery of tests, including the open-field, novel-object recognition, step-through, and Morris water maze paradigms. Oxidative and inflammatory biomarkers were assessed in serum and hippocampus, and Western blotting quantified the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2). PG improved CSD-induced impairments in exploration, recognition memory, and spatial learning; restored antioxidant capacity; reduced lipid peroxidation; enhanced Nrf2-associated antioxidant signaling; and suppressed NF-κB-mediated inflammatory activation. These findings indicate that PG alleviates cognitive deficits induced by CSD through the modulation of redox homeostasis and neuroinflammatory responses, supporting its potential as an antioxidant derivative under chronic sleep-deprivation conditions. Full article

Inflammation plays a central role in the pathogenesis of numerous diseases through the excessive production of nitric oxide (NO), prostaglandins, and pro-inflammatory cytokines. Although bromophenols from marine algae and various phenolic compounds exhibit strong anti-inflammatory activity, the biological properties of brominated vanillin derivatives remain largely unexplored. This study aimed to investigate the anti-inflammatory effects of 2-bromo-5-hydroxy-4-methoxybenzaldehyde (2B5H4M), a brominated vanillin derivative structurally similar to marine bromophenols, in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. 2B5H4M significantly reduced LPS-induced NO and PGE₂ production by suppressing the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). It also downregulated the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. Mechanistically, 2B5H4M inhibited the phosphorylation and degradation of IκB-α, thereby preventing NF-κB nuclear translocation, and reduced the phosphorylation of ERK and JNK. These findings demonstrate that 2B5H4M exerts potent anti-inflammatory effects by simultaneously blocking NF-κB and MAPK signaling pathways. Although not algae-derived, the structural resemblance of 2B5H4M to marine bromophenols highlights its potential as a marine-inspired reference compound. This work suggests that 2B5H4M may serve as a promising lead scaffold for developing new phenolic anti-inflammatory agents and provides a foundation for future mechanistic and in vivo studies. Full article

Moringa oleifera, widely recognized as the horseradish tree or drumstick tree, is classified within the Moringaceae family, which comprises 13 species predominantly distributed across tropical and subtropical regions. The plant possesses a variety of therapeutic, nutritional, and beneficial health properties, including its potential to enhance the immune system. The present work provides extensive bibliographic research addressing the chemical composition of Moringa oleifera and its immunomodulatory properties with a focus on the cellular and molecular mechanisms involved in the regulation of immune function, which is crucial in unchecked cell proliferation and metastasis. The chemical composition of Moringa oleifera, including kaempferol, chlorogenic acid, quercetin, and niazimicin, varies between different biological parts of the plant (seeds, leaves, roots, and stems). The presence of these various chemical compounds contributes to the plant’s effect on the immune response via different pathways. Several studies indicate that Moringa oleifera mitigates inflammation by suppressing key pro-inflammatory mediators, such as TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE-2), and cyclooxygenase-2 (COX-2), while simultaneously enhancing anti-inflammatory mediators through activation of PPAR-γ. Furthermore, the immunomodulatory properties and possible application in health promotion and disease prevention, especially in cancer therapy, are discussed. Studies indicate that Moringa oleifera can modulate the tumor microenvironment (TME) by reducing Treg polarization, enhancing NK cell cytotoxicity, and prompting the proliferation and clonal expansion of CD8⁺ and CD4⁺ T lymphocytes. Together, Moringa oleifera could be considered for the treatment of conditions related to immune dysregulation, such as cancer. Full article

Background: The association between oxidative stress and inflammation in obesity motivates investigation of the effects of d-limonene, gallic acid, ellagic acid, p-coumaric acid, and their mixture, which are major compounds of Callistemon citrinus, on oxidative stress and inflammation in the brains of rats fed a high-fat-sucrose diet. This study aimed to identify the specific bioactive compounds in C. citrinus leaf extract responsible for its neuroprotective effects against diet-induced oxidative stress and neuroinflammation. Methods: Forty-eight male Wistar rats were randomly divided into eight groups (n = 6). Group 1 (control) received a standard diet, while group 2 received a high-fat, high-sucrose diet (HFSD). Groups 3, 4, 5, 6, 7, and 8 were also fed HFSD supplemented with C. citrinus extract, its main compounds, and a mixture of these compounds administered once daily via oral cannula for 23 weeks. The antioxidant and pro-inflammatory enzymes, along with oxidative biomarkers, were evaluated in the brains of the rats. Results:C. citrinus leaf extract and its four main components, both separately and together, modulated the activities of catalase, superoxide dismutase, glutathione peroxidase, and paraoxonase-1. They also affected levels of reduced glutathione while decreasing the amounts of advanced oxidative protein products, malondialdehyde, and 4-hydroxynonenal. Additionally, they decreased the activities of cyclooxygenase (COX-1 and COX-2), 5-lipoxygenase, xanthine oxidase, and myeloperoxidase in the brains of rats, despite a high-fat-sucrose diet. Conclusions: These results show that the main compounds in C. citrinus leaf extract are essential for its antioxidant and anti-inflammatory effects, which help protect against oxidative stress in the brains of rats on a high-calorie diet. Full article

High-stocking-density (HD) environments can trigger systemic inflammatory responses, consequently impairing broiler growth. Given the broad anti-inflammatory properties of aspirin eugenol ester (AEE), this study investigated the effects of AEE supplementation on growth performance, immune organ indices, serum immunoglobulin levels, and hypothalamic inflammation-related markers in HD broilers. A total of 528 one-day-old male Arbor Acres (AA) broilers were randomly assigned to four groups: ND, HD, ND-AEE, and HD-AEE (ND, 14 birds/m²; HD, 22 birds/m²), with six replicate cages per treatment group over a 42-day experimental period. The results revealed that AEE significantly improved the growth performance of HD broilers. Immune organ indices, serum immunoglobulin levels, and the expression of spleen inflammatory factors was associated with the organismal inflammatory response, which manifested primarily during the late growth phase. On Day 35, AEE significantly suppressed (p < 0.05) the relative mRNA expression of p21-activated kinase 1 (PAK1) in the hypothalamus of HD broilers. On Day 42, AEE significantly reduced the relative mRNA expression of PAK1, p38 mitogen-activated protein kinase (p38MAPK), cyclooxygenase-2 (COX-2), prostaglandin E synthase 1 (mPGES-1), and interleukin-1β (IL-1β) (p < 0.05), while significantly elevating the relative mRNA expression of growth hormone-releasing hormone (GHRH) (p < 0.05). Collectively, these findings demonstrate that AEE mitigates high-density rearing-induced hypothalamic inflammation and is associated with downregulated mRNA expression of PAK1 and its downstream targets in the p38MAPK/COX-2 axis. This gene expression profile correlates with improved growth and immune function in high-density-stressed broilers, suggesting a potential regulatory link that requires further validation at the protein and functional levels. Full article

Airborne particulate matter (PM) is a major environmental pollutant that accelerates skin aging, inflammation, and barrier impairment. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has shown anti-inflammatory and cytoprotective effects, yet its role in protecting full-thickness human skin from pollution-induced damage remains unclear. In this study, human full-thickness ex vivo skin explants were topically exposed to PM (0.54 mg/cm²) and treated with CBD (6.4 mM) administered via the culture medium for 48 h. Proinflammatory mediators (interleukin-6, IL-6; matrix metalloproteinase-1, MMP-1; cyclooxygenase-2, COX-2), oxidative stress markers (reactive oxygen species, ROS; 8-hydroxy-2′-deoxyguanosine, 8-OHdG), the xenobiotic sensor aryl hydrocarbon receptor (AhR), extracellular matrix proteins (procollagen type I C-peptide, PIP; fibrillin), and the barrier protein filaggrin were quantified using ELISA and immunofluorescence. PM exposure triggered significant inflammation, oxidative stress, AhR induction, extracellular matrix degradation, and barrier disruption. CBD selectively counteracted these effects by reducing IL-6, MMP-1, COX-2, ROS, and 8-OHdG levels, downregulating AhR expression, and restoring PIP, fibrillin, and filaggrin expression. No measurable effects were observed in unstressed control tissues. These results demonstrate that CBD protects human skin from PM-induced molecular damage and supports its potential as a functional bioactive ingredient for anti-pollution applications. Full article

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality, with inflammation playing a pivotal role in its pathogenesis. Chronic inflammation in the intestine significantly increases the risk of CRC development. Main compounds participating in the inflammatory process are prostaglandins; bioactive lipids derived from arachidonic acid metabolism via the cyclooxygenase (COX) pathway. While it is well known that prostaglandin E₂ (PGE₂) promotes CRC tumorigenesis, other prostaglandins, such as PGD₂, PGF_2α, and prostacyclin (PGI₂), remain relatively underexplored. These prostaglandins may exert distinct or opposing effects on CRC development, but the current understanding of their functions is limited. Additionally, the impact of prostaglandins on immune regulation and the tumor microenvironment, is far from being fully understood. Addressing these knowledge gaps is crucial for identifying novel therapeutic targets and optimizing chemoprevention strategies. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of CRC, largely by inhibiting prostaglandin producing enzymes. However, their use is limited due to their gastrointestinal and cardiovascular side effects. Therefore, understanding the intricate role of inflammation and prostaglandin signaling in CRC is critical to develop safer and more effective chemopreventive approaches. This review summarizes the current knowledge of prostaglandins, linking inflammation and CRC. It further addresses the potential of targeting prostaglandin pathways for chemoprevention. Furthermore, we discuss emerging pharmacological targets that modulate prostaglandin production, signaling or degradation, offering promise for preventing CRC development. Full article

The aim of this study was to investigate the molecular interactions of heparin, diclofenac, and their supramolecular complexes with cyclooxygenase enzymes (COX-1 and COX-2) using computational docking techniques. Diclofenac is a widely used nonsteroidal anti-inflammatory drug (NSAID) that inhibits COX isoforms, whereas heparin is a polyanionic glycosaminoglycan with established anticoagulant and emerging anti-inflammatory properties. Supramolecular association between these agents may modulate their physicochemical behavior and target engagement. Molecular modeling, dual-drug docking, and molecular dynamics (MD) simulations were employed to characterize the interactions of heparin, diclofenac, and pre-formed heparin–diclofenac complexes with COX-1 and COX-2. Geometry optimization and lipophilicity (logP) estimates were obtained using HyperChem, while protein–ligand docking was performed in HEX using crystallographic COX structures from the Protein Data Bank. Docking poses were analyzed in Chimera, and selected complexes were refined through short MD simulations. Pre-formed heparin–diclofenac assemblies exhibited markedly enhanced docking scores toward both COX isoforms compared with single ligands. Binding orientation strongly influenced affinity: for COX-1, the heparin–diclofenac configuration yielded the most favorable interaction, whereas for COX-2 the diclofenac–heparin configuration was preferred. Both assemblies adopted binding modes distinct from free diclofenac, suggesting cooperative electrostatic and hydrophobic contacts at the enzyme surface. Supramolecular complexation also altered calculated logP values relative to the individual compounds. MD simulations supported the relative stability of the top-ranked complex–COX assemblies. These findings indicate that heparin–diclofenac assemblies may enhance and reorganize predicted COX interactions in a configuration-dependent manner and illustrate the utility of dual-drug docking for modeling potential synergistic effects. Such insights may inform the design of localized or topical formulations, potentially incorporating non-anticoagulant heparin derivatives, to achieve effective COX inhibition with reduced systemic exposure. However, the results rely on simplified heparin fragments, legacy docking tools, and short MD simulations, and should therefore be interpreted qualitatively. Experimental studies will be essential to confirm whether such supramolecular assemblies form under physiological conditions and whether they influence COX inhibition in vivo. Full article

Airborne particulate matter (PM) triggers oxidative stress and inflammation in pulmonary tissues, contributing to chronic respiratory diseases. This study evaluated the antioxidant and anti-inflammatory effects of a combined extract of Haematococcus pluvialis (H. pluvialis) and walnut shell (HW extract) and its protective efficacy against PM_2.5-induced pulmonary inflammation. Extracts mixed at different ratios (10:0–0:10, w/w) were tested using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, cell-based assays, HPLC quantification, molecular docking, and a PM_2.5-induced pulmonary inflammation mouse model. The optimized 6:4 mixture showed the strongest antioxidant activity (RC₅₀ = 0.61 ± 0.14 μg/mL) and significantly reduced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression without cytotoxicity. HPLC confirmed the presence of astaxanthin (1.714 μg/mg) and quercetin (0.722 μg/mg). Docking simulations indicated strong COX-2 binding affinities (−9.501 and −8.753 kcal/mol) through hydrogen bonding and hydrophobic interactions. In vivo, HW extract reduced leukocyte infiltration, serum IL-6 levels, and pulmonary expression of COX-2, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) while improving alveolar structure. These results suggest that HW extract exerts synergistic antioxidant and anti-inflammatory actions via dual-site COX-2 modulation, providing a promising natural therapeutic approach for mitigating PM_2.5-induced respiratory inflammation. Full article

Background/Objectives: The cerebral cortex is critical for neurological functions that are strongly affected by the aging process. Astrocytes play a central role in maintaining neurotransmitter balance and regulating antioxidant and anti-inflammatory responses, but these physiological functions may also decline with age. This study aimed to investigate the effects of melatonin, a molecule with known antioxidant, anti-inflammatory and neuroprotective properties, on astrocytes of mature cortical tissue obtained from adult Wistar rats. Methods: Primary cortical astrocyte cultures were obtained from neonatal and 90-day-old Wistar rats and treated with melatonin (300 µM for 24 h). We assessed cell viability and metabolism (MTT and extracellular lactate levels), glutamine synthetase (GS) activity, glutathione (GSH) content, release of cytokines, and the expression of genes and proteins associated with oxidative stress and inflammation by RT-qPCR and Western blotting. Results: Melatonin did not affect cell viability or lactate production. Moreover, there were no changes in GS activity, a key enzyme in glutamate metabolism, or in GSH levels, an antioxidant defense molecule synthesized by astrocytes. However, melatonin significantly reduced the expression of the nuclear factor NFκB, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS), while increasing interleukin 6 and 10 levels. Melatonin also upregulated the gene expression of the transcriptional factors Nrf2 and sirtuin 1 (SIRT1) and downregulated AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), while PGC-1α protein levels remained unchanged. A complementary analysis of astrocytes obtained from neonatal rats showed that melatonin did not change metabolic or redox parameters under basal conditions. Conclusions: Melatonin exerted anti-inflammatory effects on adult astrocyte cultures, likely through modulation of protective signaling pathways, such as Nrf2/SIRT1. These findings highlight the potential role of melatonin in preserving astrocytic function and mitigating age-related neuroinflammatory processes. Full article

Advanced glycation end products (AGEs) are compounds that accumulate in hyperglycemic states, contributing significantly to the development of diabetes and its complications, including the exacerbation of periodontal disease. We hypothesized that AGEs affect the expression of inflammatory mediators in gingival cells, thus contributing to the increased severity of periodontitis observed in diabetic patients. Thus, we stimulated the gingival epithelial carcinoma-derived cell line, Ca9-22, with AGEs and examined their effect on the expression of prostaglandin E₂ (PGE₂) and its primary synthesizing enzyme, cyclooxygenase 2 (COX2), key inflammatory mediators in periodontitis. AGEs significantly increased the expression levels of COX2 (n = 6, p < 0.001) and the production of PGE₂ (n = 5, p < 0.05) compared to untreated control and bovine serum albumin (BSA) groups. The receptor for AGEs (RAGE) inhibitor FPS-ZM1 blocked the AGEs-stimulatory effects on COX2 (n = 7, p < 0.01), PGE₂ (n = 6, p < 0.001), and Toll-like receptor 4 (TLR4) expression (n = 7, p < 0.001). Furthermore, AGEs induced the phosphorylation of protein kinase C (p-PKC) via the TLR4 pathway (n = 7, p < 0.01). Crucially, AGEs enhanced NF-κB nuclear accumulation, which was inhibited by blocking either RAGE (n = 5, p < 0.0001) or TLR4 (n = 5, p < 0.0001). In conclusion, these findings demonstrate that AGEs increase PGE₂ production in Ca9-22 cells primarily through a signaling cascade involving RAGE and the TLR4-PKC-NF-κB pathway. Our results suggest TLR4 as a critical mediator that contributes to AGEs-induced inflammation. Full article

Glucosinolate-derived metabolites play central roles in plant defense and are increasingly recognized for their pharmacological importance. Barbarea vulgaris produces a structurally diverse set of such compounds, yet their biological activities remain insufficiently explored. In this study, natural metabolites and their synthetic analogues were evaluated for antimicrobial, antibiofilm, antioxidant, and anti-inflammatory properties. Antimicrobial activity was assessed against human and plant pathogens by determining minimum inhibitory and minimum microbicidal concentrations, antibiofilm potential was examined using microplate assays, and radical scavenging activity was measured by DPPH and ABTS assays. In addition, the compounds were screened for inhibitory effects on lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). Phenolic derivatives, particularly methyl-4-hydroxyphenylethyl dithiocarbamate (2) and 2-(4-hydroxyphenyl)ethyl isothiocyanate (8), exhibited notable in vitro antibacterial activity (MIC 0.312–1.25 mg mL⁻¹ against E. coli ATCC 25922 and S. aureus ATCC 25923) and detectable antibiofilm effects. Racemic barbarin (4) preferentially inhibited LOX, underscoring its potential as an anti-inflammatory scaffold, whereas COX-2 inhibition was weak across all tested compounds. None of the metabolites showed radical scavenging activity, suggesting that their effects rely on enzyme inhibition or microbial interactions rather than nonspecific antioxidant mechanisms. This study provides an integrated evaluation of B. vulgaris metabolites, highlighting their ecological role in plant defense and their potential as scaffolds for novel antimicrobial and anti-inflammatory agents. Full article

Chronic inflammation is implicated in the development of various multifactorial diseases, including cancer, diabetes, arthritis, cardiovascular disorders, Alzheimer’s disease, and autoimmune diseases. The enzymes that play a key role in the onset of the inflammation are cyclooxygenases (COXs) and lipoxygenases (LOXs). In recent years, cinnamic acid hybrid molecules, particularly those incorporating a nitric oxide (NO) donor moiety, have attracted considerable attention as potential pharmacological agents for the treatment of multifactorial diseases. In the present study, novel cinnamic acid–nitric oxide (NO) donor hybrids were synthesized as multitarget agents and evaluated for their antioxidant, anti-inflammatory, and cytotoxic properties. In particular, hybrids 5a–i, 6a–i, 9a–i, and 11 were synthesized and evaluated as lipid peroxidation and LOX inhibitors, while selected molecules were further tested as COX-1 and COX-2 inhibitors. Hybrids 6a–i, 9a–i, and 11 that contain a NO donor moiety, were additionally tested as albumin denaturation inhibitors and for their ability to release NO. The results indicated that compound 9a is a promising multitarget agent, exhibiting the lowest IC₅₀ for LOX inhibition, significant antioxidant activity, and the highest NO donor potency. Furthermore, compound 9e demonstrated significant inhibitory activity against both COX-2 and LOX, suggesting its potential as a dual COX–LOX inhibitor. Additionally, compound 6i exhibited the strongest cytotoxic activity among the tested compounds, with EC₅₀ values ranging from 36 to 45 μM across multiple cancer cell lines. All synthesized compounds were also evaluated through in silico studies. Full article

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for managing inflammation, but they are associated with gastrointestinal and renal toxicity upon long-term use. Selective cyclooxygenase-2 (COX-2) inhibitors, or coxibs, were developed to avoid these adverse effects while maintaining anti-inflammatory efficacy. However, accumulating evidence indicates that coxibs may increase the risk of cardiovascular complications. This review explores the pathophysiological mechanisms underlying adverse cardiovascular effects in patients treated with COX-2 inhibitors. These mechanisms include an imbalance between prothrombotic and antithrombotic factors, an altered endocannabinoid metabolism, and downregulation of PPARδ, contributing to thrombosis. Additionally, COX-2 inhibition disrupts renal prostaglandin synthesis, particularly PGE2 and prostacyclins, reduces EP4 receptor expression in macrophages, promotes chemotaxis, and elevates arterial pressure via increased iNOS, ADMA, and L-NMMA activity. At the molecular level, genetic polymorphisms, matrix metalloproteinases, signaling cross-talk, and direct cardiomyocyte injury are implicated. Collectively, these alterations promote a prothrombotic state, fluid retention, enhanced vasoconstriction, impaired vasodilation, myocardial injury, cell death, and cardiac fibrosis. Despite these risks, coxibs are often prescribed without adequate cardiovascular assessment, particularly in patients with pre-existing cardiovascular risk factors. Greater awareness of these mechanisms is essential to optimize the benefit–risk ratio in clinical decision-making involving selective COX-2 inhibitors. Full article