Two key therapeutic targets in the treatment of Alzheimer's disease are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Understanding the molecular characteristics associated with cholinesterase inhibition is important for the development of new inhibitors. In this study, a chemometric framework integrating Fourier Transform Infrared (FTIR) spectroscopy, Principal Component Analysis (PCA), and region-wise Partial Least Squares Regression (PLSR) was applied to explore spectral-response relationships in newly synthesized flurbiprofen hydrazide and hydrazone derivatives. The dataset comprised 27 compounds with 1868 spectral variables covering the 4000-400 cm[-1] region and experimentally determined AChE and BuChE inhibition activities. Following SNV preprocessing, PCA was used to characterize spectral variability and define five major spectral domains: O-H/N-H, C-H, carbonyl/amide, C-O/C-N, and fingerprint regions. Region-wise PLSR models were evaluated using 5-fold cross-validation based on RMSECV and MAE-CV, with Y-randomization providing an additional assessment of the observed modeling performance. Among the investigated regions, the C-H stretching domain (3000-2800 cm[-1]) showed the most favorable relative cross-validated performance for both AChE (RMSECV = 5.49; MAE-CV = 4.02) and BuChE (RMSECV = 5.09; MAE-CV = 5.13). Y-randomization further supported the response-related performance of the C-H region, particularly for BuChE. Regression coefficient profiles provided additional spectral information for interpreting the response-related variation across the investigated regions. Overall, the FTIR-PCA-PLSR framework provides an interpretable approach for comparative assessment of spectral domains and for generating chemically testable hypotheses regarding cholinesterase inhibition in the investigated flurbiprofen derivative series.

A novel series of tris-Schiff bases of flurbiprofen has been synthesised via multi-step reactions, structures were deduced by means of HR-ESI-MS, [13]C- and [1]H-NMR spectroscopy and screened for their in vitro tyrosinase inhibitory potential. All the synthetic derivatives attributed noteworthy inhibition except compounds (11, 14 and 16), while eight compounds (5, 6, 7, 8, 19, 24, 22 and 18) were found potent comparing them with the standard kojic acid. Furthermore, the remaining nine compounds showed good to less inhibitory activity. A para-nitro containing compound 5 attributed the powerful tyrosinase inhibition through docking and normal mode analysis (NMA). It formed stable electrostatic interactions and hydrogen bonds that decline catalytic flexibility, as well as stabilising the enzyme in an inactive site. NMA showed disrupted strong intra-domain coupling and global motions, signifying a broad stabilisation of the enzyme structure. Compared to kojic acid, compound 5 displayed enhanced binding stability, lower B-factors and tighter packing. A robust correlation (R[2] = 0.8754) among the IC50 values and binding energy authenticated the computational model and its potential for rational inhibitor design.

Neuroinflammation, read as elevated levels of Interleukin-1β (IL-1β) and of its downstream signaling cascade, has been shown to play a neuropathogenic role in numerous neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Western blotting was used to determine the effects of IL-1β and its signaling cascade on Human Oligodendroglioma (HOG) and Schwann cells and to evaluate the potential therapeutic effects of Ibuprofen and Flurbiprofen on MS pathogenesis in vitro. IL-1β increased neuroinflammatory markers like TNFα, MyD88, βAPP, COX-2, and IL-6, as well as transcription factors like NFκB and STAT in HOG and Schwann cells, which in turn regulate the expression of other cytokines, resulting in the activation of the self-perpetuating Cytokine Cycle. The IL-1β treatment of HOG and Schwann cells decreased the levels of myelin Basic Protein (MBP) and synaptophysin while at the same time increasing βAPP. Autophagy markers like LAMP-2 and LC3B were downregulated. In contrast, treatment with Ibuprofen and Flurbiprofen effectively countered the harmful effects of IL-1β in MS. These in vitro studies show that IL-1β can play a possible detrimental role in facilitating neuropathogenesis, as seen in Alzheimer's and Parkinson's disease, and anti-inflammatory drugs Ibuprofen and Flurbiprofen have a potential role in modulating the neuroinflammation in MS.

Due to their poor ability to solubilize lipophilic drugs and insufficient skin adhesion, conventional hydrogels show limited application in transdermal drug delivery systems (TDDSs). Eutectogels are considered promising alternatives to hydrogels because of their excellent drug solubility, adhesion, and stability. This work reports the preparation of a high-performance double -network eutectogel using ChCl-urea deep eutectic solution as the solvent, poly (4-hydroxyphenyl methacrylate-co-acrylic acid-co-N-vinylpyrrolidone) and carboxylated cellulose nanofibers as first polymer network and second polymer network, respectively, and Zr[4+] as a physical crosslinker. Compared to conventional hydrogels, the prepared eutectogel demonstrated superior performance in TDDS, including an excellent elongation rate (> 1400%), high tensile strength (0.89 MPa), strong skin adhesion (> 60 kPa), strong self-healing capacity, and outstanding stability across the temperature range of -20 to 60 °C due to the multiple hydrogen bond interactions and metal coordination. Meanwhile, owing to the enhanced drug solubilizing effects of DES solvents and acrylate polymers, eutectogel significantly enhanced flurbiprofen drug loading and demonstrated excellent therapeutic effects through in vivo pharmacodynamics experiments, highlighting its potential as an efficient platform to facilitate transdermal therapy for chronic diseases, including arthritis, offering an effective way to develop transdermal patches for low-solubility drugs.

Myocardial ischemia-reperfusion (I/R) injury is characterized by excessive inflammatory responses and pyroptosis, a form of regulated cell death in which activation of the NLRP3 inflammasome plays a central role. Despite advances in therapeutic strategies, effective interventions targeting inflammation-driven myocardial injury remain limited. Flurbiprofen axetil, a non-selective cyclooxygenase inhibitor with well-established anti-inflammatory properties, has been widely used in clinical practice; however, its role in myocardial I/R injury and its association with inflammasome-related signaling remain incompletely understood. In this study, we investigated the cardioprotective effects of flurbiprofen axetil in a rat model of myocardial I/R injury. Histological analysis, enzyme-linked immunosorbent assay (ELISA), TdT-mediated dUTP nick-end labeling (TUNEL) staining, and Western blotting were performed to evaluate myocardial structural damage, inflammatory responses, and cardiomyocyte death. Our results demonstrated that flurbiprofen axetil significantly alleviated myocardial structural injury and reduced serum levels of CK-MB, LDH, and cTnI. In addition, levels of pro-inflammatory cytokines, including IL-1β, IL-18, and TNF-α, were markedly decreased. At the molecular level, flurbiprofen axetil treatment was associated with reduced expression of NLRP3, ASC, caspase-1, and GSDMD-N, consistent with attenuation of inflammasome-related and pyroptotic signaling. Furthermore, postconditioning tended to exhibit greater protective effects than preconditioning in attenuating inflammatory responses and myocardial injury markers, whereas both strategies showed comparable effects on cardiomyocyte death. In conclusion, flurbiprofen axetil attenuates myocardial I/R injury, and these cardioprotective effects are associated with attenuation of NLRP3 inflammasome-related and downstream pyroptotic signaling, accompanied by reduced inflammatory responses.

Topical non-steroidal anti-inflammatory drugs (NSAIDs) such as flurbiprofen and benzydamine may be used for the symptomatic relief of pharyngitis, triggered by infections. The onset and spectrum of anti-inflammatory activity of both drugs were compared in human tonsil (HTEpiC) and bronchial epithelial (BEAS-2B) cells stimulated with poly I:C against key inflammatory mediators. Cells were stimulated with poly I:C for 24 h and treated with flurbiprofen or benzydamine for 20 s, 2 min and 5 min. Production of prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), interleukin-8 (IL-8), interleukin-18 (IL-18), monocyte chemotactic protein-3 (MCP-3) and C-X-C motif chemokine ligand 10 (CXCL10), as well as cyclooxygenase-2 (COX-2) protein expression, was evaluated. Flurbiprofen significantly (p < 0.05) reduced PGE2 production and COX-2 expression in both cell types within 20 s of treatment and maintained these effects at 2 and 5 min. However, benzydamine produced delayed, inconsistent inhibition. Although both drugs reduced poly I:C induced IL-6, IL-1β, IL-8 and IL-18 production, the magnitude and onset were greater with flurbiprofen. Flurbiprofen also reduced MCP-3 and CXCL10 in both cell types, alongside significant inhibition of caspase-1 activity. Benzydamine showed limited or no effect and less inhibition of caspase-1. With rapid suppression of the COX-2/PGE2 pathway, rapid onset and a broad inhibition spectrum, flurbiprofen more comprehensively modulates inflammatory processes in epithelial respiratory models.

Background: Acute sore throat (pharyngitis) accounts for 10-30% of ambulatory visits annually. Bacterial etiology, primarily Group A Streptococcus, is confirmed in only 20-34% of cases, and inappropriate antibiotic administration remains frequent, contributing to antimicrobial resistance. Community pharmacists play a key role in symptomatic management and stewardship, but real-world practices remain underexplored. Methods: A 16-item online questionnaire surveyed 629 Italian community pharmacists via professional networks, covering demographics, diagnostic tools, symptom assessment, treatment preferences, and follow-up. Responses were analyzed using descriptive statistics and interpreted within a multidisciplinary expert framework. Results: Italian community pharmacists (n = 629), predominantly mid-career and experienced individuals, prioritize targeted symptom questioning (flu-like signs (59.96%), fever (48.73%), pain intensity (49.64%)) and medical referral over formal diagnostic tools like the Centor criteria (unused in 53.66% of cases). A total of 46.74% report performing a Strep A test in fewer than 20% of patients. Topical sprays (83.33%) and lozenges (44.69%), especially containing flurbiprofen (94.19%), dominate recommendations, followed by systemic analgesics (45.79%). For mild cases, anti-inflammatory/analgesic sprays/lozenges (35.42%) and antiseptic lozenges (35.61%) dominate, while in severe cases, drugs with anti-inflammatory or analgesic effects are often preferred (72.47%). Most pharmacists request a follow-up (73.22%). Conclusions: Italian community pharmacists report a predominantly topical-first approach focused on symptomatic treatment and referral when appropriate. Diagnostic gaps and inconsistent follow-up represent actionable targets. The findings inform training outputs prioritizing simplified triage, expanded symptom checklists, spray/lozenge optimization, and 3-5-day call-backs. This work aims to promote pharmacists' antimicrobial stewardship to reduce antibiotic use while enhancing patient-centred sore throat care in Italy's pharmacy network.

The dose-effect relationship and hemodynamic effects of oliceridine in elderly patients undergoing laparoscopic surgery remain unclear. This study evaluated the effects of different doses of oliceridine administered via patient-controlled intravenous analgesia (PCIA) on postoperative pain management in older adults with colorectal cancer. Patients were divided into three groups according to the analgesic regimen: a control group (Group C, fentanyl PCIA), a low-dose oliceridine group (Group O1), and a high-dose oliceridine group (Group O2), each comprising 50 patients. Outcomes included resting and movement numeric rating scale (NRS) scores, incidence of moderate-to-severe pain, Ramsay sedation scores, Quality of Recovery-15 (QoR-15) scores, patient satisfaction, inflammatory cytokine levels, hemodynamic and respiratory parameters, and adverse reactions. The total opioid load was similar across the three groups. Group O2 showed consistently lower resting and movement NRS scores at all observation time points (all P<0.001). It also had the lowest frequency of moderate-to-severe pain within the first 48 hours after surgery (P<0.05). In addition, patients in the O2 group achieved earlier first ambulation and had a shorter length of hospital stay than the other groups (P<0.05). Group O2 also showed a higher QoR-15 score, indicating better postoperative recovery quality (P<0.001), along with higher analgesic satisfaction (P=0.001). Inflammatory cytokine levels decreased dose-dependently (P<0.001). Hemodynamic parameters were more stable, and respiratory rate and saturation (SpO2) improved more significantly in Group O2 (P<0.05). The incidence of adverse reactions was comparable among the three groups of people (P>0.05). The number of remedial analgesia administrations within 24 hours postoperatively (0.4±0.2 times) and total flurbiprofen axetil consumption (25.0±12.5 mg) were significantly lower in Group O2 than in Groups O1 and C (P<0.05). High-dose Oliceridine PCIA provided better analgesic effects for elderly Laparoscopic Colorectal Cancer Patients after surgery, effectively reduced inflammatory response, and maintained stable Hemodynamic and Respiratory Function.