Pub Date : 2025-12-01DOI: 10.1016/j.prerep.2025.100072
Maria Laura da Cruz Castro , Flávia Monteiro Ferreira , Camila Francieli Chagas , Sttefany Viana Gomes , Renata Rebeca Pereira , Aline Meireles Coelho , Saulo Fehelberg Pinto Braga , Gabrielly Guimarães Coutinho , Vitória Louise Teixeira e Silva , Sirlaine Pio Gomes da Silva , André Talvani , Allan Jefferson Cruz Calsavara , Daniela Caldeira Costa
Sepsis-associated encephalopathy (SAE), affecting up to 70 % of patients with sepsis, is a diffuse cerebral dysfunction that correlates with higher mortality rates and long-term cognitive impairments such as memory deficits. The pathophysiology of SAE includes neuroinflammation, oxidative stress, apoptosis, microglial activation, blood-brain barrier (BBB) dysfunction, and metabolic disturbances. The compromised BBB during sepsis allows inflammatory mediators to infiltrate, increasing oxidative stress. Studies highlight the role of BBB disruption in SAE, with matrix metalloproteinase 9 (MMP-9) activity increasing BBB permeability. The antibiotic doxycycline inhibits MMP activity and shows promise in protecting BBB integrity by reducing neuroinflammation and oxidative stress. This study evaluates the impact and mechanisms underlying doxycycline treatment on cognitive function in mice with polymicrobial sepsis. Doxycycline treatment improves cognition in the animals and increases brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Doxycycline also inhibits MMP-9, reduces neuroinflammation and attenuates oxidative stress in the brain. In addition, molecular modeling suggests that doxycycline effectively binds to MMP-9. These findings suggest that doxycycline attenuates cognitive deficits, reduces neuroinflammation and oxidative stress, and inhibits MMP-9 in a mouse model of sepsis-associated encephalopathy.
{"title":"Doxycycline attenuates cognitive impairment, neuroinflammation and oxidative stress in a mouse model of sepsis-associated encephalopathy","authors":"Maria Laura da Cruz Castro , Flávia Monteiro Ferreira , Camila Francieli Chagas , Sttefany Viana Gomes , Renata Rebeca Pereira , Aline Meireles Coelho , Saulo Fehelberg Pinto Braga , Gabrielly Guimarães Coutinho , Vitória Louise Teixeira e Silva , Sirlaine Pio Gomes da Silva , André Talvani , Allan Jefferson Cruz Calsavara , Daniela Caldeira Costa","doi":"10.1016/j.prerep.2025.100072","DOIUrl":"10.1016/j.prerep.2025.100072","url":null,"abstract":"<div><div>Sepsis-associated encephalopathy (SAE), affecting up to 70 % of patients with sepsis, is a diffuse cerebral dysfunction that correlates with higher mortality rates and long-term cognitive impairments such as memory deficits. The pathophysiology of SAE includes neuroinflammation, oxidative stress, apoptosis, microglial activation, blood-brain barrier (BBB) dysfunction, and metabolic disturbances. The compromised BBB during sepsis allows inflammatory mediators to infiltrate, increasing oxidative stress. Studies highlight the role of BBB disruption in SAE, with matrix metalloproteinase 9 (MMP-9) activity increasing BBB permeability. The antibiotic doxycycline inhibits MMP activity and shows promise in protecting BBB integrity by reducing neuroinflammation and oxidative stress. This study evaluates the impact and mechanisms underlying doxycycline treatment on cognitive function in mice with polymicrobial sepsis. Doxycycline treatment improves cognition in the animals and increases brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Doxycycline also inhibits MMP-9, reduces neuroinflammation and attenuates oxidative stress in the brain. In addition, molecular modeling suggests that doxycycline effectively binds to MMP-9. These findings suggest that doxycycline attenuates cognitive deficits, reduces neuroinflammation and oxidative stress, and inhibits MMP-9 in a mouse model of sepsis-associated encephalopathy.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-03DOI: 10.1016/j.prerep.2025.100071
Rejuan Islam , Subhajit Ghosh , Subarna Thakur , Tilak Saha
Background
Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting women of reproductive age and is often associated with metabolic and inflammatory complications. Abutilon indicum (L.) Sweet, a small medicinal shrub widely used in traditional medicine systems, including Traditional Chinese Medicine (TCM), has been employed to manage a variety of health complications. Recent findings suggest that its seed extract may offer therapeutic potential against PCOS. This study aimed to investigate the bioactive constituents and underlying pharmacological mechanisms of the methanolic extract of A. indicum seeds (MEAS) in PCOS using a combination of GC-MS based profiling, network pharmacology, and molecular docking analyses.
Methodology
Phytochemical profiling of MEAS was performed using GC-MS, followed by ADMET-based screening to identify drug-like compounds. Target genes of MEAS phytochemicals were predicted via STP and SEA servers, while PCOS-related genes were retrieved from OMIM and DisGeNET databases. Common targets were intersected with differentially expressed genes (DEGs) derived from a publicly available PCOS-related gene expression dataset. These genes were further analyzed for protein–protein interaction (PPI), Gene Ontology (GO), and KEGG pathway enrichment. Molecular docking and MM/GBSA calculations were conducted to validate compound–target interactions.
Results
GC-MS analysis of MEAS revealed 19 phytochemical compounds, of which 13 satisfied drug-likeness criteria based on ADMET profiling. Database screening identified 110 targets associated with PCOS. Integration of these targets with DEGs resulted in the identification of 10 key PCOS-related genes, including ESR1, HMOX1, CYP17A1, PTAFR, and TLR2. Pathway enrichment analysis revealed a significant enrichment of inflammation-related pathways, oxidative stress, and insulin resistance. Furthermore, molecular docking and MMGBSA results confirmed that phytocompounds like thymidine, 9,12-octadecadienoic acid (Z, Z)-, methyl ester, 9,12-octadecadienoic acid (Z, Z)-, octadecanoic acid, and 9,12-octadecadienoic acid (Z, Z)-, 2-hydroxy-1-(hydroxymethyl) ethyl have strong binding efficacy with the PCOS-related target proteins.
Conclusion
This integrative study elucidates the multi-target pharmacological mechanisms of A. indicum seed constituents in modulating key pathways implicated in PCOS. The findings support the potential application of A. indicum within TCM-based approaches for managing PCOS and its complications.
{"title":"Therapeutic potential of Abutilon indicum (L.) Sweet seed extract in PCOS: Insights from mass spectrometry, network pharmacology, and molecular docking","authors":"Rejuan Islam , Subhajit Ghosh , Subarna Thakur , Tilak Saha","doi":"10.1016/j.prerep.2025.100071","DOIUrl":"10.1016/j.prerep.2025.100071","url":null,"abstract":"<div><h3>Background</h3><div>Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting women of reproductive age and is often associated with metabolic and inflammatory complications. <em>Abutilon indicum (L.)</em> Sweet, a small medicinal shrub widely used in traditional medicine systems, including Traditional Chinese Medicine (TCM), has been employed to manage a variety of health complications. Recent findings suggest that its seed extract may offer therapeutic potential against PCOS. This study aimed to investigate the bioactive constituents and underlying pharmacological mechanisms of the methanolic extract of <em>A. indicum</em> seeds (MEAS) in PCOS using a combination of GC-MS based profiling, network pharmacology, and molecular docking analyses.</div></div><div><h3>Methodology</h3><div>Phytochemical profiling of MEAS was performed using GC-MS, followed by ADMET-based screening to identify drug-like compounds. Target genes of MEAS phytochemicals were predicted via STP and SEA servers, while PCOS-related genes were retrieved from OMIM and DisGeNET databases. Common targets were intersected with differentially expressed genes (DEGs) derived from a publicly available PCOS-related gene expression dataset. These genes were further analyzed for protein–protein interaction (PPI), Gene Ontology (GO), and KEGG pathway enrichment. Molecular docking and MM/GBSA calculations were conducted to validate compound–target interactions.</div></div><div><h3>Results</h3><div>GC-MS analysis of MEAS revealed 19 phytochemical compounds, of which 13 satisfied drug-likeness criteria based on ADMET profiling. Database screening identified 110 targets associated with PCOS. Integration of these targets with DEGs resulted in the identification of 10 key PCOS-related genes, including ESR1, HMOX1, CYP17A1, PTAFR, and TLR2. Pathway enrichment analysis revealed a significant enrichment of inflammation-related pathways, oxidative stress, and insulin resistance. Furthermore, molecular docking and MMGBSA results confirmed that phytocompounds like thymidine, 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, methyl ester, 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, octadecanoic acid, and 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, 2-hydroxy-1-(hydroxymethyl) ethyl have strong binding efficacy with the PCOS-related target proteins.</div></div><div><h3>Conclusion</h3><div>This integrative study elucidates the multi-target pharmacological mechanisms of <em>A. indicum</em> seed constituents in modulating key pathways implicated in PCOS. The findings support the potential application of <em>A. indicum</em> within TCM-based approaches for managing PCOS and its complications.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.prerep.2025.100069
Yupeng Cui , Xiaoyan Liu , Russel J. Reiter
Ample experimental evidence supports the protective effect of melatonin against oxidative damage and fatigue induced by overload athletic training. This article aims to review recent research on the protective effect and mechanisms of melatonin against oxidative stress induced by intensive training and competition, and to provide theoretical support for its application and future research directions. The mechanism of melatonin action involves around direct scavenger of reactive oxygen species, aggregation in mitochondria, and activating signal pathways by binding to receptors. Mitochondria may be one of the most important targets of melatonin in preventing oxidative stress, histiocytic damage and metabolic disorders induced by intensive training. Given the important role of redox signaling agents in activating different signal transduction systems to elicit adaptive changes to exercise stimuli, a phased short-term mode of melatonin supplementation tailored to athletes’ redox status and training load is recommended.
{"title":"Supplemental use of melatonin to protect against oxidative stress induced by intensive athletic training and competition","authors":"Yupeng Cui , Xiaoyan Liu , Russel J. Reiter","doi":"10.1016/j.prerep.2025.100069","DOIUrl":"10.1016/j.prerep.2025.100069","url":null,"abstract":"<div><div>Ample experimental evidence supports the protective effect of melatonin against oxidative damage and fatigue induced by overload athletic training. This article aims to review recent research on the protective effect and mechanisms of melatonin against oxidative stress induced by intensive training and competition, and to provide theoretical support for its application and future research directions. The mechanism of melatonin action involves around direct scavenger of reactive oxygen species, aggregation in mitochondria, and activating signal pathways by binding to receptors. Mitochondria may be one of the most important targets of melatonin in preventing oxidative stress, histiocytic damage and metabolic disorders induced by intensive training. Given the important role of redox signaling agents in activating different signal transduction systems to elicit adaptive changes to exercise stimuli, a phased short-term mode of melatonin supplementation tailored to athletes’ redox status and training load is recommended.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-29DOI: 10.1016/j.prerep.2025.100070
Harshita Krishnatreyya , Hemanga Hazarika
Ocular drug delivery is significant as it delivers drugs to one of the most vital and intricate structures in the human body, the eye, which is currently the site for increased occurrences of diseases like dryness, glaucoma, age related macular degeneration, diabetic retinopathy etc. It is noticeable that drugs delivered at a controlled rate, over prolonged periods of time, are the most effective in treating ocular complications by improving drug therapeutic efficacy and ocular bioavailability. In this article, we provide a summary of the importance of controlled release (CR) systems in ocular delivery, its significance, and the most popular types of CR formulations. Factors to be considered while designing CR drug formulations and the essential mechanisms involved in CR of drugs have been briefed. The significance of diversely sourced biodegradable polymers and the impact of their physicochemical characteristics on drug release is discussed. Previously conducted research on CR formulations, few currently available and marketed ocular CR products and patents; the advantages, disadvantages and challenges of CR systems in ocular tissues are debated. With smarter developments arising to benefit people, there is no definitive endpoint to the progressing research that develops innovative and effective strategies to provide CR of ocular drugs with diminished side effects.
{"title":"Controlled release approaches in ocular drug delivery","authors":"Harshita Krishnatreyya , Hemanga Hazarika","doi":"10.1016/j.prerep.2025.100070","DOIUrl":"10.1016/j.prerep.2025.100070","url":null,"abstract":"<div><div>Ocular drug delivery is significant as it delivers drugs to one of the most vital and intricate structures in the human body, the eye, which is currently the site for increased occurrences of diseases like dryness, glaucoma, age related macular degeneration, diabetic retinopathy etc. It is noticeable that drugs delivered at a controlled rate, over prolonged periods of time, are the most effective in treating ocular complications by improving drug therapeutic efficacy and ocular bioavailability. In this article, we provide a summary of the importance of controlled release (CR) systems in ocular delivery, its significance, and the most popular types of CR formulations. Factors to be considered while designing CR drug formulations and the essential mechanisms involved in CR of drugs have been briefed. The significance of diversely sourced biodegradable polymers and the impact of their physicochemical characteristics on drug release is discussed. Previously conducted research on CR formulations, few currently available and marketed ocular CR products and patents; the advantages, disadvantages and challenges of CR systems in ocular tissues are debated. With smarter developments arising to benefit people, there is no definitive endpoint to the progressing research that develops innovative and effective strategies to provide CR of ocular drugs with diminished side effects.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-19DOI: 10.1016/j.prerep.2025.100068
Ilhem Dallali , Ahmed Hasan , Feyza Alyu Altınok , Nurcan Bektas Turkmen , Yusuf Ozturk
Background
Diabetic neuropathic pain is a persistent and debilitating complication of diabetes with limited treatments. Melatonin shows promise in pain modulation, though its underlying antinociceptive mechanisms remain unclear. This study investigated the analgesic efficacy of melatonin in alleviating streptozotocin-induced neuropathic pain in rats and explored the involvement of noradrenergic pathways.
Methods
Neuropathic pain was induced in male Sprague-Dawley rats via a single intravenous injection of streptozotocin (50 mg/kg). Melatonin (50 mg/kg, i.p.) was administered daily for two weeks. Gabapentin (50 mg/kg, i.p.) served as a positive control. Mechanical allodynia and thermal hyperalgesia were assessed using the e-Von Frey and Hargreaves tests, respectively, while locomotor activity was evaluated using an activity cage. To evaluate metabolic effects, blood glucose levels were monitored throughout the study. Adrenergic antagonists’ prazosin (α1, 10 mg/kg), yohimbine (α2, 4 mg/kg), and propranolol (β, 5 mg/kg) were administered prior to the final melatonin dose to assess noradrenergic involvement.
Results
Streptozotocin-induced diabetic rats exhibited pronounced mechanical and thermal hypersensitivity. Subacute melatonin treatment significantly reduced nociceptive responses and improved locomotor activity, showing efficacy comparable to gabapentin. It did not alter blood glucose levels, indicating a neutral metabolic effect. The analgesic effects of melatonin were attenuated by adrenergic antagonists, implicating noradrenergic signaling in its mechanism of action.
Conclusions
Melatonin exerts significant antiallodynic and antihyperalgesic effects in diabetic neuropathic rats, likely mediated via noradrenergic receptor pathways. Its neutral impact on glycemic control, combined with potential mood-regulating properties, supports its promise as a therapeutic candidate for managing diabetic neuropathic pain, pending clinical validation.
{"title":"Melatonin alleviates streptozotocin-induced neuropathic pain in rat model: Involvement of noradrenergic receptor pathways","authors":"Ilhem Dallali , Ahmed Hasan , Feyza Alyu Altınok , Nurcan Bektas Turkmen , Yusuf Ozturk","doi":"10.1016/j.prerep.2025.100068","DOIUrl":"10.1016/j.prerep.2025.100068","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic neuropathic pain is a persistent and debilitating complication of diabetes with limited treatments. Melatonin shows promise in pain modulation, though its underlying antinociceptive mechanisms remain unclear. This study investigated the analgesic efficacy of melatonin in alleviating streptozotocin-induced neuropathic pain in rats and explored the involvement of noradrenergic pathways.</div></div><div><h3>Methods</h3><div>Neuropathic pain was induced in male Sprague-Dawley rats via a single intravenous injection of streptozotocin (50 mg/kg). Melatonin (50 mg/kg, <em>i.p.</em>) was administered daily for two weeks. Gabapentin (50 mg/kg, <em>i.p.</em>) served as a positive control. Mechanical allodynia and thermal hyperalgesia were assessed using the e-Von Frey and Hargreaves tests, respectively, while locomotor activity was evaluated using an activity cage. To evaluate metabolic effects, blood glucose levels were monitored throughout the study. Adrenergic antagonists’ prazosin (α1, 10 mg/kg), yohimbine (α2, 4 mg/kg), and propranolol (β, 5 mg/kg) were administered prior to the final melatonin dose to assess noradrenergic involvement.</div></div><div><h3>Results</h3><div>Streptozotocin-induced diabetic rats exhibited pronounced mechanical and thermal hypersensitivity. Subacute melatonin treatment significantly reduced nociceptive responses and improved locomotor activity, showing efficacy comparable to gabapentin. It did not alter blood glucose levels, indicating a neutral metabolic effect. The analgesic effects of melatonin were attenuated by adrenergic antagonists, implicating noradrenergic signaling in its mechanism of action.</div></div><div><h3>Conclusions</h3><div>Melatonin exerts significant antiallodynic and antihyperalgesic effects in diabetic neuropathic rats, likely mediated via noradrenergic receptor pathways. Its neutral impact on glycemic control, combined with potential mood-regulating properties, supports its promise as a therapeutic candidate for managing diabetic neuropathic pain, pending clinical validation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Curcumin, a polyphenolic chemical derived from Curcuma longa, has long been used as a culinary ingredient and in traditional medicine because of its unique orange--yellow color. Anti-inflammatory, antioxidant, antibacterial, and chemopreventive qualities are only a few of its many pharmacological activities. The increasing relevance of curcumin in pharmacogenomics is examined in this review, with particular attention given to how it affects gene expression and drug metabolism. Curcumin alters important enzymes and pathways, including drug transporters and cytochrome P450s, which impacts how the body breaks down medications. Additionally, it controls transcription factors such as Nrf2 and NF-κB, which affect genes related to inflammation and detoxification. Curcumin is a promising adjuvant in personalized medicine since it can improve therapeutic efficacy and decrease adverse drug reactions through these mechanisms. Its potential application in precision treatment procedures is supported by its capacity to fine-tune metabolic and signalling pathways. This review aims to investigate the possible function of curcumin in pharmacogenomics, namely, in modifying individual reactions to medications depending on genetic variants, as well as how it affects drug metabolism and gene expression.
{"title":"Curcumin as a modulator of drug metabolism and gene expression: Implications for pharmacogenomics","authors":"Igbayilola Yusuff Dimeji , Hamidu Lawan Jabba , Ngabea Murtala , Adekola Saheed Ayodeji","doi":"10.1016/j.prerep.2025.100067","DOIUrl":"10.1016/j.prerep.2025.100067","url":null,"abstract":"<div><div>Curcumin, a polyphenolic chemical derived from <em>Curcuma longa</em>, has long been used as a culinary ingredient and in traditional medicine because of its unique orange--yellow color. Anti-inflammatory, antioxidant, antibacterial, and chemopreventive qualities are only a few of its many pharmacological activities. The increasing relevance of curcumin in pharmacogenomics is examined in this review, with particular attention given to how it affects gene expression and drug metabolism. Curcumin alters important enzymes and pathways, including drug transporters and cytochrome P450s, which impacts how the body breaks down medications. Additionally, it controls transcription factors such as Nrf2 and NF-κB, which affect genes related to inflammation and detoxification. Curcumin is a promising adjuvant in personalized medicine since it can improve therapeutic efficacy and decrease adverse drug reactions through these mechanisms. Its potential application in precision treatment procedures is supported by its capacity to fine-tune metabolic and signalling pathways. This review aims to investigate the possible function of curcumin in pharmacogenomics, namely, in modifying individual reactions to medications depending on genetic variants, as well as how it affects drug metabolism and gene expression.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-22DOI: 10.1016/j.prerep.2025.100066
Irene Ebosereme Ainyanbhor , Great Iruoghene Edo , Ali B.M. Ali , Patrick Othuke Akpoghelie , Morenike Olufunmilayo Akpo , Emad Yousif , Joseph Oghenewogaga Owheruo , Ufuoma Augustina Igbuku , Oluwatobi Victoria Obayomi , Arthur Efeoghene Athan Essaghah , Dilber Uzun Ozsahin , Huzaifa Umar , Dina S. Ahmed , Ahmed A. Alamiery
Background
Ibuprofen, the third most frequently prescribed over-the-counter drug globally, is used for treatment of inflammation, pain and pyrexia.
Objective
This review discusses its synthesis, mechanism of action, pharmacokinetics, pharmacodynamics, derivatives, prospect as well as its environmental impact as an emerging contaminant.
Findings
Its anti-inflammatory property stems from its reduction in synthesis of prostaglandins in inflammatory processes through the inhibition of COX-1 and COX-2 enzyme. However, adverse effect such as gastrointestinal ulceration, myocardial infarction and renal failure has been associated with the use of this drug especially during prolonged usage. Hence, the need for structural modification of this drug reduce or eliminate its adverse effect and also improved efficacy. Research report indicates derivative of ibuprofen from its structural modification results in novel drugs for relief of pain and inflammation with little or no side effects associated with the parent drug. Research also propose the prodrug Ibu-GLVL as a prospective drug for the treatment and management of Alzheimer disease. Despite the classical uses and prospect of this drug, its adverse environmental impact due to observed toxicity in organisms as well as possible contamination of food chain needs to be properly addressed.
Conclusion
This review emphasizes the need to develop more sophisticated methods for effective removal of emerging contaminant including ibuprofen in WWTP since most traditional WWTP are ineffective in removal of such contaminant. This will reduce and may eliminate the adverse environmental effect posed by this emerging contaminant due its wide usage across the globe.
{"title":"Ibuprofen: A review on its synthesis, mechanism of action, pharmacological properties, and environmental impact","authors":"Irene Ebosereme Ainyanbhor , Great Iruoghene Edo , Ali B.M. Ali , Patrick Othuke Akpoghelie , Morenike Olufunmilayo Akpo , Emad Yousif , Joseph Oghenewogaga Owheruo , Ufuoma Augustina Igbuku , Oluwatobi Victoria Obayomi , Arthur Efeoghene Athan Essaghah , Dilber Uzun Ozsahin , Huzaifa Umar , Dina S. Ahmed , Ahmed A. Alamiery","doi":"10.1016/j.prerep.2025.100066","DOIUrl":"10.1016/j.prerep.2025.100066","url":null,"abstract":"<div><h3>Background</h3><div>Ibuprofen, the third most frequently prescribed over-the-counter drug globally, is used for treatment of inflammation, pain and pyrexia.</div></div><div><h3>Objective</h3><div>This review discusses its synthesis, mechanism of action, pharmacokinetics, pharmacodynamics, derivatives, prospect as well as its environmental impact as an emerging contaminant.</div></div><div><h3>Findings</h3><div>Its anti-inflammatory property stems from its reduction in synthesis of prostaglandins in inflammatory processes through the inhibition of COX-1 and COX-2 enzyme. However, adverse effect such as gastrointestinal ulceration, myocardial infarction and renal failure has been associated with the use of this drug especially during prolonged usage. Hence, the need for structural modification of this drug reduce or eliminate its adverse effect and also improved efficacy. Research report indicates derivative of ibuprofen from its structural modification results in novel drugs for relief of pain and inflammation with little or no side effects associated with the parent drug. Research also propose the prodrug Ibu-GLVL as a prospective drug for the treatment and management of Alzheimer disease. Despite the classical uses and prospect of this drug, its adverse environmental impact due to observed toxicity in organisms as well as possible contamination of food chain needs to be properly addressed.</div></div><div><h3>Conclusion</h3><div>This review emphasizes the need to develop more sophisticated methods for effective removal of emerging contaminant including ibuprofen in WWTP since most traditional WWTP are ineffective in removal of such contaminant. This will reduce and may eliminate the adverse environmental effect posed by this emerging contaminant due its wide usage across the globe.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The intensive use of veterinary antibiotics, particularly bacteriostatic agents and ionophores, represents an increasing ecotoxicological concern for aquatic ecosystems. This study integrates scientometric analysis with a systematic literature review specifically aimed at identifying gaps in experimental research addressing the effects of these pharmaceuticals on aquatic organisms through biomarker-based assessments. A total of 648 publications published between 1968 and 2024 were screened; however, only 20 in vivo studies involving 10 aquatic species (7 vertebrates and 3 invertebrates) met the inclusion criteria, of which 17 investigated bacteriostatic antibiotics and 3 ionophores. Acute exposure designs predominated (35 %), followed by subchronic (30 %), chronic (15 %), and combined acute–chronic (20 %) assays. Reported environmental concentrations ranged from nanograms to hundreds of micrograms per liter, whereas experimental exposures frequently reached milligram-per-liter levels — in some cases exceeding environmental concentrations by several orders of magnitude. Observed effects included oxidative stress, immunological alterations, reproductive impairment, embryotoxicity, and histopathological damage. The findings demonstrate a disproportionate reliance on standard model organisms, particularly Danio rerio, and a notable scarcity of studies involving native or ecologically relevant species. This review highlights a critical need for future research to adopt chronic exposure scenarios, incorporate native species, environmentally relevant concentrations, and apply standardized- sensitive biomarkers. Addressing these gaps is essential to advance the environmental risk assessment of veterinary antibiotics and to support more effective and evidence-based environmental policymaking.
{"title":"Veterinary bacteriostatic and ionophore antibiotics in aquatic organisms: A systematic review and scientometric analysis of biomarker and exposure concentrations","authors":"Thaís Pereira Nascimento , Andrea Carina Crupkin , Mirta Luján Menone","doi":"10.1016/j.prerep.2025.100065","DOIUrl":"10.1016/j.prerep.2025.100065","url":null,"abstract":"<div><div>The intensive use of veterinary antibiotics, particularly bacteriostatic agents and ionophores, represents an increasing ecotoxicological concern for aquatic ecosystems. This study integrates scientometric analysis with a systematic literature review specifically aimed at identifying gaps in experimental research addressing the effects of these pharmaceuticals on aquatic organisms through biomarker-based assessments. A total of 648 publications published between 1968 and 2024 were screened; however, only 20 in vivo studies involving 10 aquatic species (7 vertebrates and 3 invertebrates) met the inclusion criteria, of which 17 investigated bacteriostatic antibiotics and 3 ionophores. Acute exposure designs predominated (35 %), followed by subchronic (30 %), chronic (15 %), and combined acute–chronic (20 %) assays. Reported environmental concentrations ranged from nanograms to hundreds of micrograms per liter, whereas experimental exposures frequently reached milligram-per-liter levels — in some cases exceeding environmental concentrations by several orders of magnitude. Observed effects included oxidative stress, immunological alterations, reproductive impairment, embryotoxicity, and histopathological damage. The findings demonstrate a disproportionate reliance on standard model organisms, particularly <em>Danio rerio</em>, and a notable scarcity of studies involving native or ecologically relevant species. This review highlights a critical need for future research to adopt chronic exposure scenarios, incorporate native species, environmentally relevant concentrations, and apply standardized- sensitive biomarkers. Addressing these gaps is essential to advance the environmental risk assessment of veterinary antibiotics and to support more effective and evidence-based environmental policymaking.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-11DOI: 10.1016/j.prerep.2025.100064
Hamad Hasan , Alzamka M.A. Almabruk , Mustapha Belaidi , Saleh Bufarwa
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide, underscoring the urgent need for novel, multi-target therapeutics. This study systematically evaluates Dieckol, a phlorotannin from brown algae, using a dry-lab pipeline integrating quantum chemical calculations, transcriptomic data mining, network pharmacology, molecular docking, molecular dynamics (MD), and ADMET-toxicity prediction. Density Functional Theory (DFT) analysis revealed favorable electronic properties for selective bio-interactions, including a narrow HOMO–LUMO gap (0.119 eV) and high electron-accepting capacity. From 313 predicted targets and 7325 HCC-associated genes, 33 overlapping genes were identified, enriched in cell cycle, apoptosis, and oncogenic signaling pathways, particularly hsa05225 (HCC pathway). Protein–protein interaction and drug–target–pathway networks highlighted CDKN1A, TP53, DNMT1, AURKA, and MAPK1 as central targets. Molecular docking demonstrated strong binding affinities with key HCC-related proteins (CDKN1A: −10.3 kcal/mol; TP53: −9.5 kcal/mol), supported by stable MD simulations and favorable MMGBSA binding energies (e.g., DNMT1: −362.9 kcal/mol). Dieckol also modulated immune-infiltration signatures of key genes (e.g., PIK3R1, NRAS, CDKN2A), suggesting immunomodulatory potential. Gene and protein expression analyses validated differential upregulation of hub targets in tumor vs. normal liver tissues. In silico ADME profiling revealed low oral bioavailability, poor GI absorption, and selective CYP2C9 inhibition, while toxicity predictions showed no carcinogenicity or genotoxicity but flagged moderate renal and dermal risks. Collectively, our findings position Dieckol as a promising multi-target agent for HCC intervention, warranting further in vitro and in vivo validation.
{"title":"Dieckol from brown algae targeting the Hepatocellular Carcinoma pathway: A computational pharmacology study","authors":"Hamad Hasan , Alzamka M.A. Almabruk , Mustapha Belaidi , Saleh Bufarwa","doi":"10.1016/j.prerep.2025.100064","DOIUrl":"10.1016/j.prerep.2025.100064","url":null,"abstract":"<div><div><em>Hepatocellular carcinoma</em> (<strong>HCC</strong>) is a leading cause of cancer mortality worldwide, underscoring the urgent need for novel, multi-target therapeutics. This study systematically evaluates Dieckol, a phlorotannin from brown algae, using a dry-lab pipeline integrating quantum chemical calculations, transcriptomic data mining, network pharmacology, molecular docking, molecular dynamics (<strong>MD</strong>), and ADMET-toxicity prediction. Density Functional Theory (<strong>DFT</strong>) analysis revealed favorable electronic properties for selective bio-interactions, including a narrow HOMO–LUMO gap (0.119 eV) and high electron-accepting capacity. From 313 predicted targets and 7325 HCC-associated genes, 33 overlapping genes were identified, enriched in cell cycle, apoptosis, and oncogenic signaling pathways, particularly hsa05225 (HCC pathway). Protein–protein interaction and drug–target–pathway networks highlighted CDKN1A, TP53, DNMT1, AURKA, and MAPK1 as central targets. Molecular docking demonstrated strong binding affinities with key HCC-related proteins (CDKN1A: −10.3 kcal/mol; TP53: −9.5 kcal/mol), supported by stable MD simulations and favorable MMGBSA binding energies (e.g., DNMT1: −362.9 kcal/mol). Dieckol also modulated immune-infiltration signatures of key genes (e.g., PIK3R1, NRAS, CDKN2A), suggesting immunomodulatory potential. Gene and protein expression analyses validated differential upregulation of hub targets in tumor vs. normal liver tissues. In silico ADME profiling revealed low oral bioavailability, poor GI absorption, and selective CYP2C9 inhibition, while toxicity predictions showed no carcinogenicity or genotoxicity but flagged moderate renal and dermal risks. Collectively, our findings position Dieckol as a promising multi-target agent for HCC intervention, warranting further in <em>vitro</em> and in <em>vivo</em> validation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1016/j.prerep.2025.100063
Anders Larsson, Anna-Karin Hamberg, Jonathan Cedernaes, Mathias Karlsson
Monitoring assay performance using traditional internal quality control (IQC), and external quality assurance (EQA) methods has limitations, particularly regarding sample commutability. This study investigates the use of patient-derived valproate data, specifically median and quartile values, as a complementary approach to quality control in a clinical laboratory setting. A retrospective analysis was performed on 13,336 routine serum valproate results collected between January 2004 and December 2024 at Akademiska Hospital, Uppsala. Valproate was analyzed using immunoassays on the Architect ci8200 platform until 2020, after which testing was transferred to the Roche Cobas Pro c503. Annual patient medians and quartiles were calculated, and seasonal patterns were evaluated. Method transfer and performance were assessed using internal controls and patient data. The number of annual test requests declined modestly over the study period. Median valproate concentrations remained stable across the 21-year period, with minimal variability in interquartile ranges. The 0.10 and 0.90 percentiles showed slightly higher fluctuation, likely due to sample timing variation rather than analytical drift. Seasonal analysis revealed no clinically relevant variation. The method transfer in 2021 did not introduce observable shifts in patient medians, supporting good method comparability. Longitudinal monitoring of patient median and quartile valproate concentrations provides a robust, clinically meaningful tool for supplementary assay performance surveillance. This approach is particularly suitable for therapeutic drug monitoring, where treatment protocols and target ranges are stable over time.
使用传统的内部质量控制(IQC)和外部质量保证(EQA)方法监测检测性能具有局限性,特别是在样品可交换性方面。本研究调查了丙戊酸盐患者来源数据的使用,特别是中位数和四分位数值,作为临床实验室环境中质量控制的补充方法。回顾性分析了2004年1月至2024年12月在乌普萨拉Akademiska医院收集的13336例丙戊酸常规血清结果。在Architect ci8200平台上使用免疫分析法分析丙戊酸盐,直到2020年,之后测试转移到罗氏Cobas Pro c503。计算年度患者中位数和四分位数,并评估季节性模式。使用内部控制和患者数据评估方法转移和性能。在研究期间,年度测试请求的数量略有下降。丙戊酸盐浓度中位数在21年间保持稳定,在四分位数范围内变化最小。0.10和0.90百分位数显示出稍高的波动,可能是由于样本时间变化而不是分析漂移。季节分析显示无临床相关的变化。2021年的方法转移没有引入可观察到的患者中位数变化,支持良好的方法可比性。纵向监测患者丙戊酸盐浓度中位数和四分位数提供了一个强大的,有临床意义的辅助检测性能监测工具。这种方法特别适用于治疗性药物监测,治疗方案和靶标范围随着时间的推移是稳定的。
{"title":"Long term monitoring of serum valproate assays using patient median values show stable test results over a period of more than 20 years","authors":"Anders Larsson, Anna-Karin Hamberg, Jonathan Cedernaes, Mathias Karlsson","doi":"10.1016/j.prerep.2025.100063","DOIUrl":"10.1016/j.prerep.2025.100063","url":null,"abstract":"<div><div>Monitoring assay performance using traditional internal quality control (IQC), and external quality assurance (EQA) methods has limitations, particularly regarding sample commutability. This study investigates the use of patient-derived valproate data, specifically median and quartile values, as a complementary approach to quality control in a clinical laboratory setting. A retrospective analysis was performed on 13,336 routine serum valproate results collected between January 2004 and December 2024 at Akademiska Hospital, Uppsala. Valproate was analyzed using immunoassays on the Architect ci8200 platform until 2020, after which testing was transferred to the Roche Cobas Pro c503. Annual patient medians and quartiles were calculated, and seasonal patterns were evaluated. Method transfer and performance were assessed using internal controls and patient data. The number of annual test requests declined modestly over the study period. Median valproate concentrations remained stable across the 21-year period, with minimal variability in interquartile ranges. The 0.10 and 0.90 percentiles showed slightly higher fluctuation, likely due to sample timing variation rather than analytical drift. Seasonal analysis revealed no clinically relevant variation. The method transfer in 2021 did not introduce observable shifts in patient medians, supporting good method comparability. Longitudinal monitoring of patient median and quartile valproate concentrations provides a robust, clinically meaningful tool for supplementary assay performance surveillance. This approach is particularly suitable for therapeutic drug monitoring, where treatment protocols and target ranges are stable over time.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}