Pub Date : 2026-02-09DOI: 10.1007/s10787-026-02122-8
Ayansh Kaushik, Romanpreet Kaur, Shamsher Singh
{"title":"Syringic acid exerts neuroprotective effect in a rat model of traumatic brain injury through modulation of the MAPK signaling pathway.","authors":"Ayansh Kaushik, Romanpreet Kaur, Shamsher Singh","doi":"10.1007/s10787-026-02122-8","DOIUrl":"https://doi.org/10.1007/s10787-026-02122-8","url":null,"abstract":"","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1007/s10787-026-02119-3
Sara Kazemzadeh, Mahdieh Raeeszadeh, Loghman Akradi
Plant-derived bioactive compounds are increasingly considered as safer alternatives to synthetic drugs in wound management. This study aimed to comparatively evaluate the wound-healing efficacy of Pistacia atlantica (bene tree) leaf extract ointment versus phenytoin in a rat skin wound model. This experimental interventional study was conducted using Pistacia atlantica leaf extract. The extract was first analyzed by gas chromatography-mass spectrometry (GC-MS) and subsequently formulated into herbal ointments. Thirty-five rats were anesthetized using ketamine and xylazine, and standardized excisional skin wounds were created on the dorsal region. Animals were randomly assigned into four groups: control (C), 5% Pistacia ointment (P5), 25% Pistacia ointment (P25), and phenytoin (F). Treatments were applied for 21 days. Wound photographs were taken on days 1, 3, 5, 7, 14, and 21, and wound areas were measured using ImageJ software. At the end of the study, tissue samples were collected in 10% formalin for histopathological analysis with hematoxylin-eosin and Masson's trichrome staining. A significant decrease in body weight was observed in the phenytoin group compared with all other groups (p < 0.05). Wound contraction and healing percentages were highest in the P25 and F groups, followed by the P5 and control groups. Histopathological analysis of P25-treated wounds, consistent with the F group, revealed a significant enhancement in epithelialization, angiogenesis, granulation tissue formation, fibroblast proliferation, collagen deposition, and hair follicle regeneration compared with the C group (p < 0.001). Furthermore, inflammatory cell infiltration during the healing process was markedly and significantly reduced in the P25 group compared to the other study groups (p < 0.001). GC-MS analysis revealed that 1,2,3-benzenetriol (antibacterial), cis-13-octadecenoic acid (anti-inflammatory), and phytol (antimicrobial, anti-inflammatory, antioxidant) were the predominant compounds in the extract. The results indicated that wound healing using an ointment containing Pistacia atlantica leaf extract occurred in a dose-dependent manner and accelerated the healing process through histopathological mechanism without adverse effects compared with phenytoin. The findings support its potential as a safe and effective phytotherapeutic alternative for wound management.
{"title":"Comparative effects of Pistacia atlantica leaf and phenytoin ointment on rat skin wound healing: histopathological changes and bioactive compounds.","authors":"Sara Kazemzadeh, Mahdieh Raeeszadeh, Loghman Akradi","doi":"10.1007/s10787-026-02119-3","DOIUrl":"https://doi.org/10.1007/s10787-026-02119-3","url":null,"abstract":"<p><p>Plant-derived bioactive compounds are increasingly considered as safer alternatives to synthetic drugs in wound management. This study aimed to comparatively evaluate the wound-healing efficacy of Pistacia atlantica (bene tree) leaf extract ointment versus phenytoin in a rat skin wound model. This experimental interventional study was conducted using Pistacia atlantica leaf extract. The extract was first analyzed by gas chromatography-mass spectrometry (GC-MS) and subsequently formulated into herbal ointments. Thirty-five rats were anesthetized using ketamine and xylazine, and standardized excisional skin wounds were created on the dorsal region. Animals were randomly assigned into four groups: control (C), 5% Pistacia ointment (P5), 25% Pistacia ointment (P25), and phenytoin (F). Treatments were applied for 21 days. Wound photographs were taken on days 1, 3, 5, 7, 14, and 21, and wound areas were measured using ImageJ software. At the end of the study, tissue samples were collected in 10% formalin for histopathological analysis with hematoxylin-eosin and Masson's trichrome staining. A significant decrease in body weight was observed in the phenytoin group compared with all other groups (p < 0.05). Wound contraction and healing percentages were highest in the P25 and F groups, followed by the P5 and control groups. Histopathological analysis of P25-treated wounds, consistent with the F group, revealed a significant enhancement in epithelialization, angiogenesis, granulation tissue formation, fibroblast proliferation, collagen deposition, and hair follicle regeneration compared with the C group (p < 0.001). Furthermore, inflammatory cell infiltration during the healing process was markedly and significantly reduced in the P25 group compared to the other study groups (p < 0.001). GC-MS analysis revealed that 1,2,3-benzenetriol (antibacterial), cis-13-octadecenoic acid (anti-inflammatory), and phytol (antimicrobial, anti-inflammatory, antioxidant) were the predominant compounds in the extract. The results indicated that wound healing using an ointment containing Pistacia atlantica leaf extract occurred in a dose-dependent manner and accelerated the healing process through histopathological mechanism without adverse effects compared with phenytoin. The findings support its potential as a safe and effective phytotherapeutic alternative for wound management.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: Centaurea lycopifolia Boiss. et Kotschy (Asteraceae) is traditionally used in folk medicine for wound healing. This study aimed to develop and pharmacologically evaluate a novel oral microemulsion containing C. lycopifolia extract, focusing on its analgesic and anti-inflammatory effects in rodent models.
Methods: The extract, obtained from aerial parts of the plant, was characterized by LC-MS/MS. A microemulsion formulation was developed for oral administration. Antinociceptive activity was evaluated via hot plate (HP) and tail flick (TF) tests to assess central and spinal effects, respectively. Anti-inflammatory activity was assessed using carrageenan-induced paw edema, quantified by plethysmometry and Randall-Selitto tests.
Results: LC-MS/MS analysis identified quinic acid, chlorogenic acid, and protocatechuic acid as major phytoconstituents. In both HP and TF tests, the C. lycopifolia microemulsion demonstrated significantly stronger antinociceptive effects than aspirin. Similarly, its anti-inflammatory activity was comparable to aspirin. These pharmacological effects are possibly associated with the synergistic actions of the phenolic acids present in the extract.
Conclusions: The C. lycopifolia-loaded microemulsion exhibited strong in vivo analgesic and anti-inflammatory activity, supporting its potential as a phytopharmaceutical candidate for inflammatory pain. The use of both central and peripheral pain models provided a robust pharmacodynamic basis for its therapeutic potential. Overall, these findings highlight the relevance of phenolic-rich phytochemicals in oral delivery systems for inflammation-related disorders.
{"title":"In vitro and in vivo evaluation of an oral microemulsion formulation of Centaurea lycopifolia Boiss. Et Kotschy extract for analgesic and anti-inflammatory effects in a carrageenan-induced model.","authors":"Sonia Ebrahimi, Umay Merve Güven Bölgen, Serpil Demirci Kayıran, Tilbe Çevikelli, Mehmet Boğa, Fazilet Aksu","doi":"10.1007/s10787-026-02124-6","DOIUrl":"https://doi.org/10.1007/s10787-026-02124-6","url":null,"abstract":"<p><strong>Purpose: </strong>Centaurea lycopifolia Boiss. et Kotschy (Asteraceae) is traditionally used in folk medicine for wound healing. This study aimed to develop and pharmacologically evaluate a novel oral microemulsion containing C. lycopifolia extract, focusing on its analgesic and anti-inflammatory effects in rodent models.</p><p><strong>Methods: </strong>The extract, obtained from aerial parts of the plant, was characterized by LC-MS/MS. A microemulsion formulation was developed for oral administration. Antinociceptive activity was evaluated via hot plate (HP) and tail flick (TF) tests to assess central and spinal effects, respectively. Anti-inflammatory activity was assessed using carrageenan-induced paw edema, quantified by plethysmometry and Randall-Selitto tests.</p><p><strong>Results: </strong>LC-MS/MS analysis identified quinic acid, chlorogenic acid, and protocatechuic acid as major phytoconstituents. In both HP and TF tests, the C. lycopifolia microemulsion demonstrated significantly stronger antinociceptive effects than aspirin. Similarly, its anti-inflammatory activity was comparable to aspirin. These pharmacological effects are possibly associated with the synergistic actions of the phenolic acids present in the extract.</p><p><strong>Conclusions: </strong>The C. lycopifolia-loaded microemulsion exhibited strong in vivo analgesic and anti-inflammatory activity, supporting its potential as a phytopharmaceutical candidate for inflammatory pain. The use of both central and peripheral pain models provided a robust pharmacodynamic basis for its therapeutic potential. Overall, these findings highlight the relevance of phenolic-rich phytochemicals in oral delivery systems for inflammation-related disorders.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1007/s10787-026-02125-5
Zeeshan Ahmad, Mushtaq Ahmad Mir, Muhammad Shahid, Nasreena Bashir, Alam Zeb, Mehreen Ghufran, Falak Naz, Muhammad Ayaz
Diabetes mellitus (DM) is a chronic metabolic disorder with substantial global health implications. This study investigated the therapeutic potential of Bukiniczia cabulica (Boiss.) Lincz. against hyperglycemia and pain-related conditions. The polyphenolic profile of the crude methanolic extract (Bc.Cme) was characterized using HPLC-DAD. Its inhibitory activity against α-glucosidase and α-amylase, along with the in-silico binding affinity of identified phytochemicals, was assessed through molecular docking. The anti-diabetic effects of Bc.Cme were evaluated in alloxan-induced diabetic mice, while its antinociceptive activity was tested using tonic visceral (acetic acid-induced writhing) and acute thermal nociception (hot-plate) models. Anti-neuropathic efficacy was further examined in vincristine- and streptozotocin (STZ)-induced peripheral neuropathy. Bc.Cme demonstrated strong enzyme inhibition, suppressing α-glucosidase activity by 87.23% at 1 mg/ml and showing potent α-amylase inhibition (IC50 = 29.53 µg/ml). Docking analysis supported favorable interactions between major phenolic constituents and these enzymes. In vivo, Bc.Cme (150 mg/kg) significantly reduced blood glucose levels over four weeks in alloxan-induced diabetic mice. In pain models, doses of 50-200 mg/kg markedly decreased writhing responses and increased nociceptive latency. Additionally, Bc.Cme produced dose-dependent attenuation of static and cold allodynia, as well as heat hyperalgesia, in both vincristine- and STZ-induced neuropathy models. Overall, B. cabulica exhibits notable anti-diabetic, antinociceptive, and anti-neuropathic effects, likely mediated by its polyphenolic constituents through metabolic enzyme inhibition and modulation of pain pathways. The extract shows therapeutic promise for managing DM and its associated neuropathic complications.
{"title":"Bukiniczia cabulica (Boiss.) Lincz. ameliorate diabetes-induced neuropathy: analgesic, anti-diabetic and anti-neuropathic using enzyme inhibitory, molecular docking and in-vivo studies.","authors":"Zeeshan Ahmad, Mushtaq Ahmad Mir, Muhammad Shahid, Nasreena Bashir, Alam Zeb, Mehreen Ghufran, Falak Naz, Muhammad Ayaz","doi":"10.1007/s10787-026-02125-5","DOIUrl":"https://doi.org/10.1007/s10787-026-02125-5","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a chronic metabolic disorder with substantial global health implications. This study investigated the therapeutic potential of Bukiniczia cabulica (Boiss.) Lincz. against hyperglycemia and pain-related conditions. The polyphenolic profile of the crude methanolic extract (Bc.Cme) was characterized using HPLC-DAD. Its inhibitory activity against α-glucosidase and α-amylase, along with the in-silico binding affinity of identified phytochemicals, was assessed through molecular docking. The anti-diabetic effects of Bc.Cme were evaluated in alloxan-induced diabetic mice, while its antinociceptive activity was tested using tonic visceral (acetic acid-induced writhing) and acute thermal nociception (hot-plate) models. Anti-neuropathic efficacy was further examined in vincristine- and streptozotocin (STZ)-induced peripheral neuropathy. Bc.Cme demonstrated strong enzyme inhibition, suppressing α-glucosidase activity by 87.23% at 1 mg/ml and showing potent α-amylase inhibition (IC<sub>50</sub> = 29.53 µg/ml). Docking analysis supported favorable interactions between major phenolic constituents and these enzymes. In vivo, Bc.Cme (150 mg/kg) significantly reduced blood glucose levels over four weeks in alloxan-induced diabetic mice. In pain models, doses of 50-200 mg/kg markedly decreased writhing responses and increased nociceptive latency. Additionally, Bc.Cme produced dose-dependent attenuation of static and cold allodynia, as well as heat hyperalgesia, in both vincristine- and STZ-induced neuropathy models. Overall, B. cabulica exhibits notable anti-diabetic, antinociceptive, and anti-neuropathic effects, likely mediated by its polyphenolic constituents through metabolic enzyme inhibition and modulation of pain pathways. The extract shows therapeutic promise for managing DM and its associated neuropathic complications.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1007/s10787-026-02108-6
Akshad Balde, Rasool Abdul Nazeer
Background: Animal venoms are rich in bioactive peptides with potential therapeutic properties. Among marine toxins, jellyfish venoms are underexplored for anti-inflammatory applications. This study aims to identify and evaluate a peptide derived from the jellyfish toxin CfTX-B, for its anti-inflammatory potential.
Methods: Peptide selection was conducted through an integrated computational-experimental workflow comprising PeptideRanker bioactivity prediction, ToxinPred toxicity screening, SwissADME pharmacokinetic evaluation, and multi-target molecular docking against NLRP3, caspase-1, XO, and IL-1β, followed by LC-MS/MS confirmation of proteolytic stability. The peptide's antioxidant activity was validated through XO inhibition assays. Cytotoxicity and anti-inflammatory effects were tested in human dermal fibroblasts (HDFs) co-stimulated with lipopolysaccharide (LPS) and monosodium urate (MSU) crystals. FITC-labeling studies assessed intracellular peptide uptake. Further, the inflammation suppressing effects of the peptide were studied on in vivo rat model of gouty arthritis.
Results: The CfTX-B derived tetrapeptide (WPAW) revealed highest predicted bioactivity scores, favorable ADMET characteristics, and resistance to simulated gastrointestinal digestion. The peptide also showed strong binding to NLRP3, caspase-1, XO, and low predicted toxicity. XO inhibition assays confirmed antioxidant activity. In HDFs, the peptide showed no cytotoxicity up to 125 µM. Treatment with peptide significantly reduced nitric oxide (14.05 ± 0.24 µM) and reactive oxygen species (0.32 ± 0.009 RFI). ELISA revealed lowered IL-1β levels (53.54 ± 3.05 pg/ml). Protein expression studies showed downregulation of NLRP3, and pP65 levels, indicating effective suppression of inflammasome activation. The peptide reduced serum XO activity, IL-1β levels and suppressed joint inflammation in gout induced rats.
Conclusions: The tetrapeptide derived from jellyfish venom, exhibits strong anti-inflammatory and antioxidant activity through NLRP3 inflammasome inhibition. These results support its potential for development as a therapeutic for chronic inflammatory diseases.
{"title":"Inflammation suppressing activity of jellyfish toxin-derived peptide via downregulation of ROS/NF-κB/NLRP3 signaling in LPS/MSU induced fibroblasts in vitro and in vivo gouty arthritis model.","authors":"Akshad Balde, Rasool Abdul Nazeer","doi":"10.1007/s10787-026-02108-6","DOIUrl":"https://doi.org/10.1007/s10787-026-02108-6","url":null,"abstract":"<p><strong>Background: </strong>Animal venoms are rich in bioactive peptides with potential therapeutic properties. Among marine toxins, jellyfish venoms are underexplored for anti-inflammatory applications. This study aims to identify and evaluate a peptide derived from the jellyfish toxin CfTX-B, for its anti-inflammatory potential.</p><p><strong>Methods: </strong>Peptide selection was conducted through an integrated computational-experimental workflow comprising PeptideRanker bioactivity prediction, ToxinPred toxicity screening, SwissADME pharmacokinetic evaluation, and multi-target molecular docking against NLRP3, caspase-1, XO, and IL-1β, followed by LC-MS/MS confirmation of proteolytic stability. The peptide's antioxidant activity was validated through XO inhibition assays. Cytotoxicity and anti-inflammatory effects were tested in human dermal fibroblasts (HDFs) co-stimulated with lipopolysaccharide (LPS) and monosodium urate (MSU) crystals. FITC-labeling studies assessed intracellular peptide uptake. Further, the inflammation suppressing effects of the peptide were studied on in vivo rat model of gouty arthritis.</p><p><strong>Results: </strong>The CfTX-B derived tetrapeptide (WPAW) revealed highest predicted bioactivity scores, favorable ADMET characteristics, and resistance to simulated gastrointestinal digestion. The peptide also showed strong binding to NLRP3, caspase-1, XO, and low predicted toxicity. XO inhibition assays confirmed antioxidant activity. In HDFs, the peptide showed no cytotoxicity up to 125 µM. Treatment with peptide significantly reduced nitric oxide (14.05 ± 0.24 µM) and reactive oxygen species (0.32 ± 0.009 RFI). ELISA revealed lowered IL-1β levels (53.54 ± 3.05 pg/ml). Protein expression studies showed downregulation of NLRP3, and pP65 levels, indicating effective suppression of inflammasome activation. The peptide reduced serum XO activity, IL-1β levels and suppressed joint inflammation in gout induced rats.</p><p><strong>Conclusions: </strong>The tetrapeptide derived from jellyfish venom, exhibits strong anti-inflammatory and antioxidant activity through NLRP3 inflammasome inhibition. These results support its potential for development as a therapeutic for chronic inflammatory diseases.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1007/s10787-026-02129-1
Kesong Zhang, Honghao Ren, Xiaodong Ren, Pengfei Wen, Ke Xu, Lin Liu, Peng Xu, Ming Zhang, Zhi Yang, Mingyi Yang
<p><strong>Objective: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) have emerged as a critical therapeutic class for the management of osteoarthritis (OA). Nonetheless, there remains a notable deficiency in large-scale, real-world evidence regarding the safety profile of NSAIDs in individuals with OA. This study employed real-world drug monitoring methods to comprehensively assess the adverse events (AEs) reported by OA patients when using NSAIDs.</p><p><strong>Methods: </strong>This analytical study is grounded in AEs data systematically gathered through the FDA Adverse Event Reporting System (FAERS) surveillance program. The main focus of this study is to assess the AEs reported by OA patients when using NSAIDs. The analysis encompassed a range of commonly prescribed NSAIDs, including Ibuprofen, Naproxen, Diclofenac, Celecoxib, Rofecoxib, and Piroxicam, as commonly employed in clinical settings. The study spans a 20-year observation period, from the first quarter of 2004 to the fourth quarter of 2024. An unbalanced analysis method was adopted to investigate the AEs reported with the use of NSAIDs in OA patients, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Furthermore, the study delineated the relevant system organ categories (SOC) for the identified AEs, utilizing the FAERS database. A Time-to-Onset (TTO) analysis was also conducted to systematically evaluate the temporal relationship between NSAID exposure and the onset of AEs.</p><p><strong>Results: </strong>In addition to the commonly observed AEs, such as gastrointestinal disturbances, renal toxicity, and cardiovascular complications, our study also reported some less common AEs during the treatment of OA with NSAIDs. It is worth noting that during the treatment of OA, reports of anemia was observed with Ibuprofen. The inappropriate antidiuretic hormone secretion and respiratory failure were reported with Naproxen in OA. The sciatica, glossodynia, lip dryness, and rheumatic fever were reported with Diclofenac in OA. The ischemic stroke, facial edema, cerebrovascular disorders, and toxic skin eruptions were reported with Celecoxib in OA. The cerebrovascular accidents and depression were reported with Rofecoxib in OA. The anemia, alveolitis, and erythema multiforme were reported with Piroxicam in OA. These AEs encompass a broad range of systemic disorders, including those affecting the blood and lymphatic system, endocrine system, respiratory, thoracic, and mediastinal systems, nervous system, musculoskeletal and connective tissues, as well as the skin, subcutaneous tissue, and psychiatric health. TTO analysis classified Diclofenac-associated gastric ulcer and Ibuprofen-associated dyspepsia as adhering to an early-failure model. All remaining drug-event combinations conformed to a random-failure model.</p><p><strong>Conclusion: </strong>This study c
{"title":"Evaluating adverse events reported for non-steroidal anti-inflammatory drugs in osteoarthritis: a real-world pharmacovigilance study.","authors":"Kesong Zhang, Honghao Ren, Xiaodong Ren, Pengfei Wen, Ke Xu, Lin Liu, Peng Xu, Ming Zhang, Zhi Yang, Mingyi Yang","doi":"10.1007/s10787-026-02129-1","DOIUrl":"https://doi.org/10.1007/s10787-026-02129-1","url":null,"abstract":"<p><strong>Objective: </strong>Non-steroidal anti-inflammatory drugs (NSAIDs) have emerged as a critical therapeutic class for the management of osteoarthritis (OA). Nonetheless, there remains a notable deficiency in large-scale, real-world evidence regarding the safety profile of NSAIDs in individuals with OA. This study employed real-world drug monitoring methods to comprehensively assess the adverse events (AEs) reported by OA patients when using NSAIDs.</p><p><strong>Methods: </strong>This analytical study is grounded in AEs data systematically gathered through the FDA Adverse Event Reporting System (FAERS) surveillance program. The main focus of this study is to assess the AEs reported by OA patients when using NSAIDs. The analysis encompassed a range of commonly prescribed NSAIDs, including Ibuprofen, Naproxen, Diclofenac, Celecoxib, Rofecoxib, and Piroxicam, as commonly employed in clinical settings. The study spans a 20-year observation period, from the first quarter of 2004 to the fourth quarter of 2024. An unbalanced analysis method was adopted to investigate the AEs reported with the use of NSAIDs in OA patients, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Furthermore, the study delineated the relevant system organ categories (SOC) for the identified AEs, utilizing the FAERS database. A Time-to-Onset (TTO) analysis was also conducted to systematically evaluate the temporal relationship between NSAID exposure and the onset of AEs.</p><p><strong>Results: </strong>In addition to the commonly observed AEs, such as gastrointestinal disturbances, renal toxicity, and cardiovascular complications, our study also reported some less common AEs during the treatment of OA with NSAIDs. It is worth noting that during the treatment of OA, reports of anemia was observed with Ibuprofen. The inappropriate antidiuretic hormone secretion and respiratory failure were reported with Naproxen in OA. The sciatica, glossodynia, lip dryness, and rheumatic fever were reported with Diclofenac in OA. The ischemic stroke, facial edema, cerebrovascular disorders, and toxic skin eruptions were reported with Celecoxib in OA. The cerebrovascular accidents and depression were reported with Rofecoxib in OA. The anemia, alveolitis, and erythema multiforme were reported with Piroxicam in OA. These AEs encompass a broad range of systemic disorders, including those affecting the blood and lymphatic system, endocrine system, respiratory, thoracic, and mediastinal systems, nervous system, musculoskeletal and connective tissues, as well as the skin, subcutaneous tissue, and psychiatric health. TTO analysis classified Diclofenac-associated gastric ulcer and Ibuprofen-associated dyspepsia as adhering to an early-failure model. All remaining drug-event combinations conformed to a random-failure model.</p><p><strong>Conclusion: </strong>This study c","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1007/s10787-025-02066-5
Yaping Huang, Qing Zhou, Chengjie Ke, Maohua Chen
Background: New targeted drugs, including biologics and Janus kinase inhibitors (JAKi), have been approved for the treatment of atopic dermatitis (AD). Given their widespread clinical use, a comprehensive real-world study of their adverse events (AEs) is warranted.
Objectives: This study aims to characterize of new targeted drugs related AEs, and to compare the AE profiles of biologics and JAKi.
Methods: Disproportionality metrics, including the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean, were employed to determine AE signals. The most recent case reports were all included, and data was included until third quarter of 2024.
Results: A total of 99,043 biologics-related and 3,897 JAKi-related AEs were identified. Biologics-specific AEs, including injection reaction and eye disorders, were worthy noted. Several JAKi specific AEs also need to be noticed, including infection, gastrointestinal perforation, precancerous condition, pulmonary thrombosis, embolism venous, and pulmonary tuberculosis. Biologics exhibited more number of positive AE signals compared to JAKi, but the serious AEs are more frequently reported in JAKi than biologics (P < 0.01).
Conclusion: Our study could provide a comprehensive safety overview of biologics and JAKi during AD treatment, and provide valued evidence for healthcare professionals to select these drugs for AD patients.
{"title":"Postmarketing adverse events of biologics and Janus kinase inhibitors in patients with atopic dermatitis.","authors":"Yaping Huang, Qing Zhou, Chengjie Ke, Maohua Chen","doi":"10.1007/s10787-025-02066-5","DOIUrl":"10.1007/s10787-025-02066-5","url":null,"abstract":"<p><strong>Background: </strong>New targeted drugs, including biologics and Janus kinase inhibitors (JAKi), have been approved for the treatment of atopic dermatitis (AD). Given their widespread clinical use, a comprehensive real-world study of their adverse events (AEs) is warranted.</p><p><strong>Objectives: </strong>This study aims to characterize of new targeted drugs related AEs, and to compare the AE profiles of biologics and JAKi.</p><p><strong>Methods: </strong>Disproportionality metrics, including the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean, were employed to determine AE signals. The most recent case reports were all included, and data was included until third quarter of 2024.</p><p><strong>Results: </strong>A total of 99,043 biologics-related and 3,897 JAKi-related AEs were identified. Biologics-specific AEs, including injection reaction and eye disorders, were worthy noted. Several JAKi specific AEs also need to be noticed, including infection, gastrointestinal perforation, precancerous condition, pulmonary thrombosis, embolism venous, and pulmonary tuberculosis. Biologics exhibited more number of positive AE signals compared to JAKi, but the serious AEs are more frequently reported in JAKi than biologics (P < 0.01).</p><p><strong>Conclusion: </strong>Our study could provide a comprehensive safety overview of biologics and JAKi during AD treatment, and provide valued evidence for healthcare professionals to select these drugs for AD patients.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1007/s10787-026-02126-4
Abril Bernadette Martínez Rizo, Oscar Isaac Correa Polanco, Valeria García Martínez, Fabiola Villa de la Torre, Mario Alberto Ramírez-Camacho, Rocio Borges-Argáez, Eunice Yáñez-Barrientos, Alan Alexander Gonzalez-Ibarra, Angel Josabad Alonso-Castro, Claribel Huchin Chan, Victor Ermilo Arana Argáez
Introduction: Tecoma stans (T. stans) is traditionally employed in folk medicine for the management of inflammatory conditions; however, its pharmacological properties and underlying mechanisms of action remain insufficiently characterized.
Aim: This study aimed to evaluate the anti-inflammatory, antioxidant, and cytoprotective effects of the methanolic flower extract of T. stans using both in vitro and in vivo models, with particular emphasis on cytokines, modulation, oxidative stress markers, and lipid-derived inflammatory mediators.
Methodology: Cytotoxicity and hemotoxicity were assessed using MTT reduction and hemolysis assays, respectively. Anti-inflammatory activity was evaluated employing carrageenan-induced paw oedema and xylene-induced ear oedema models. Modulation of cytokine (TNF-α, IL-1β, IL-6, IL-10) was determined in both in vivo and in vitro models. Additionally, the effects of the extract on nitric oxide (NO), hydrogen peroxide (H2O2), leukotriene B4 (LTB4), and prostaglandin E2 (PGE2) production were analyzed.
Results: T. stans extract exhibited no cytotoxic or hemolytic effects, maintaining cell viability above 90%. It significantly attenuated inflammatory responses in edema models, reduced pro-inflammatory cytokines and mediator levels, and increased IL-10 production. Furthermore, the extract markedly decreased NO and H2O2 generation, indicating a reduction in oxidative stress.
Conclusions: These findings support the anti-inflammatory and antioxidant potential of T. stans, mediated through cytokine modulation, attenuation of oxidative stress, and partial inhibition of COX/LOX pathways. Collectively, its pharmacological profile highlights its potential as a natural therapeutic agent for the management of inflammatory disorders.
{"title":"Anti-inflammatory, antioxidant, and antinociceptive properties of methanolic flower extracts of Tecoma stans: a promising natural therapeutic agent.","authors":"Abril Bernadette Martínez Rizo, Oscar Isaac Correa Polanco, Valeria García Martínez, Fabiola Villa de la Torre, Mario Alberto Ramírez-Camacho, Rocio Borges-Argáez, Eunice Yáñez-Barrientos, Alan Alexander Gonzalez-Ibarra, Angel Josabad Alonso-Castro, Claribel Huchin Chan, Victor Ermilo Arana Argáez","doi":"10.1007/s10787-026-02126-4","DOIUrl":"https://doi.org/10.1007/s10787-026-02126-4","url":null,"abstract":"<p><strong>Introduction: </strong>Tecoma stans (T. stans) is traditionally employed in folk medicine for the management of inflammatory conditions; however, its pharmacological properties and underlying mechanisms of action remain insufficiently characterized.</p><p><strong>Aim: </strong>This study aimed to evaluate the anti-inflammatory, antioxidant, and cytoprotective effects of the methanolic flower extract of T. stans using both in vitro and in vivo models, with particular emphasis on cytokines, modulation, oxidative stress markers, and lipid-derived inflammatory mediators.</p><p><strong>Methodology: </strong>Cytotoxicity and hemotoxicity were assessed using MTT reduction and hemolysis assays, respectively. Anti-inflammatory activity was evaluated employing carrageenan-induced paw oedema and xylene-induced ear oedema models. Modulation of cytokine (TNF-α, IL-1β, IL-6, IL-10) was determined in both in vivo and in vitro models. Additionally, the effects of the extract on nitric oxide (NO), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), leukotriene B<sub>4</sub> (LTB<sub>4</sub>), and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) production were analyzed.</p><p><strong>Results: </strong>T. stans extract exhibited no cytotoxic or hemolytic effects, maintaining cell viability above 90%. It significantly attenuated inflammatory responses in edema models, reduced pro-inflammatory cytokines and mediator levels, and increased IL-10 production. Furthermore, the extract markedly decreased NO and H<sub>2</sub>O<sub>2</sub> generation, indicating a reduction in oxidative stress.</p><p><strong>Conclusions: </strong>These findings support the anti-inflammatory and antioxidant potential of T. stans, mediated through cytokine modulation, attenuation of oxidative stress, and partial inhibition of COX/LOX pathways. Collectively, its pharmacological profile highlights its potential as a natural therapeutic agent for the management of inflammatory disorders.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05DOI: 10.1007/s10787-026-02134-4
Hafiz Aamir Ali Kharl, Muhammad Naeem, Shakira Ghazanfar, Arifa Mehreen, Hasnain Haider, Sumel Ashique, Sabina Yasmin, Fatimah M Al-Salem, Md Yousuf Ansari
Inflammation and oxidative stress are involved in the physiological changes associated with many chronic diseases, which has led to sustained interest in small molecules with pleiotropic properties. As part of this effort, this study reports the synthesis and evaluation of six chalcones. These six synthesized derivatives were produced using acetophenone and benzaldehyde, and structures were characterised through nuclear magnetic resonance (NMR) spectral analysis and Fourier transform infrared (FTIR) spectroscopy. The compounds were tested for their in-vitro antioxidant properties using the DPPH free radical scavenging assay and anti-inflammatory and analgesic properties using an in-vivo model in rats and carrageenan-induced paw edema, heat-induced hyperalgesia, and mechanical allodynia.Computational finding by using AutoDockVina protocol against target enzyme (COX-II) (PDB: 3LN1), where the compounds 3B, 2B, and 1A exhibited strong binding affinities of - 9.8 kcal/mol, - 9.2 kcal/mol, and - 9.2 kcal/mol, respectively.Among these compounds, compound 3B exhibited the highest antioxidant activity, demonstrating an efficacy percentage of 78.34% and an IC50 value of 7.86μg/ml. The chalcone derivatives were also assessed for their effectiveness in carrageenan-induced hyperalgesia, a model used to study pain response. Compound 1A significantly increased latency periods at 30, 60, 90, and 120 min compared to compounds 2B and 3B, suggesting its potential analgesic properties. Furthermore, compound 3B significantly reduced allodynia response at 120 min, indicating its potential to alleviate mechanical sensitivity.These findings suggest that chalcone derivatives, particularly 2B and 3B, hold strong potential as lead compounds for developing novel COX-2-targeted anti-inflammatory and antioxidant therapeutics. This study offers a comprehensive preclinical framework for chalcone-based drug discovery targeting inflammation and oxidative stress. This study emphasizes structure-dependent variations in chalcones, which present potential leads and are worthy of further exploration.
{"title":"Computationally guided synthesis and biological profiling of chalcones as antioxidant and anti-inflammatory activities.","authors":"Hafiz Aamir Ali Kharl, Muhammad Naeem, Shakira Ghazanfar, Arifa Mehreen, Hasnain Haider, Sumel Ashique, Sabina Yasmin, Fatimah M Al-Salem, Md Yousuf Ansari","doi":"10.1007/s10787-026-02134-4","DOIUrl":"https://doi.org/10.1007/s10787-026-02134-4","url":null,"abstract":"<p><p>Inflammation and oxidative stress are involved in the physiological changes associated with many chronic diseases, which has led to sustained interest in small molecules with pleiotropic properties. As part of this effort, this study reports the synthesis and evaluation of six chalcones. These six synthesized derivatives were produced using acetophenone and benzaldehyde, and structures were characterised through nuclear magnetic resonance (NMR) spectral analysis and Fourier transform infrared (FTIR) spectroscopy. The compounds were tested for their in-vitro antioxidant properties using the DPPH free radical scavenging assay and anti-inflammatory and analgesic properties using an in-vivo model in rats and carrageenan-induced paw edema, heat-induced hyperalgesia, and mechanical allodynia.Computational finding by using AutoDockVina protocol against target enzyme (COX-II) (PDB: 3LN1), where the compounds 3B, 2B, and 1A exhibited strong binding affinities of - 9.8 kcal/mol, - 9.2 kcal/mol, and - 9.2 kcal/mol, respectively.Among these compounds, compound 3B exhibited the highest antioxidant activity, demonstrating an efficacy percentage of 78.34% and an IC<sub>50</sub> value of 7.86μg/ml. The chalcone derivatives were also assessed for their effectiveness in carrageenan-induced hyperalgesia, a model used to study pain response. Compound 1A significantly increased latency periods at 30, 60, 90, and 120 min compared to compounds 2B and 3B, suggesting its potential analgesic properties. Furthermore, compound 3B significantly reduced allodynia response at 120 min, indicating its potential to alleviate mechanical sensitivity.These findings suggest that chalcone derivatives, particularly 2B and 3B, hold strong potential as lead compounds for developing novel COX-2-targeted anti-inflammatory and antioxidant therapeutics. This study offers a comprehensive preclinical framework for chalcone-based drug discovery targeting inflammation and oxidative stress. This study emphasizes structure-dependent variations in chalcones, which present potential leads and are worthy of further exploration.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}