Pub Date : 2026-06-01Epub Date: 2026-01-12DOI: 10.1016/j.prerep.2026.100076
Roberto Andreatini , José Carlos Fernandes Galduróz
Currently, there is growing concern about the translational value of data originating from preclinical studies and some very interesting proposals to overcome this gap have been made (e.g., ARRIVE). However, some relevant differences between methodologies used in clinical and preclinical studies are still not addressed, such the limited use of behavioural scales, the clear definition of case and non-case, and the consideration the individual response in preclinical studies. In this article, five strategies are proposed to reduce this gap.
{"title":"Five proposals to increase translational value of animal models of neuropsychiatry disorders","authors":"Roberto Andreatini , José Carlos Fernandes Galduróz","doi":"10.1016/j.prerep.2026.100076","DOIUrl":"10.1016/j.prerep.2026.100076","url":null,"abstract":"<div><div>Currently, there is growing concern about the translational value of data originating from preclinical studies and some very interesting proposals to overcome this gap have been made (e.g., ARRIVE). However, some relevant differences between methodologies used in clinical and preclinical studies are still not addressed, such the limited use of behavioural scales, the clear definition of case and non-case, and the consideration the individual response in preclinical studies. In this article, five strategies are proposed to reduce this gap.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100076"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978279","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 : 2026-06-01Epub Date: 2026-01-14DOI: 10.1016/j.prerep.2026.100077
Syed Haris Omar , Md Ahsan Ghani
Background
The incidence of neurodegenerative disorders is increasing globally, and although treatments exist, few are effective in slowing the rate of cognitive/functional decline associated with these conditions. The standardised Ginkgo biloba extract EGb-761 has been studied for possible neuroprotection, however the findings have varied significantly.
Aim and Objective
This systematic review and meta-analysis examined the cognitive, functional and behavioural effects of EGb-761 in adults suffering from Alzheimer's disease, vascular dementia or mild cognitive impairment and evaluated the strength of evidence.
Methods
PRISMA 2020 guidelines were followed for the preparation of this systematic review. The study was also registered at PROSPERO (CRD420251207465). Randomised and quasi-randomised controlled trials published between 2000 and 2025 were identified via a search of 5 major databases. A variety of cognitive, behavioural, and functional measures were analysed using standardised mean differences or mean differences with 95 % confidence intervals. The I² statistic was used to determine the level of heterogeneity between studies. All statistical analyses were completed using Review Manager 5.4.
Results
Eighteen studies representing 7558 participants were included in the final analysis, 10 of which provided sufficient data for inclusion in a meta-analysis. While there were statistically insignificant changes in cognitive function, the pooled SMD of ADAS Cog was 0.03 with a 95 % CI of −0.27–0.33, with high levels of heterogeneity (I² = 80 %). Similarly, the pooled MD of behavioural outcomes as measured by GERRI was 0.06 with a 95 % CI of −0.07–0.20, showing no statistically significant difference. The pooled SMD of functional outcomes as measured by ADL was 0.02 with a 95 % CI of −0.17–0.21, again showing no statistically significant difference, with low levels of heterogeneity (I² = 7 %).
Conclusion
Ginkgo biloba extract had small and clinically meaningless effects on cognition, behaviour and functional ability. The quality of the evidence ranged from low to moderate, suggesting further large-scale, well-controlled studies are required to establish whether it may be useful in the treatment of neurodegenerative disorders.
{"title":"Cognitive and functional effects of Ginkgo biloba in neurodegenerative disorders: Systematic review and meta analysis","authors":"Syed Haris Omar , Md Ahsan Ghani","doi":"10.1016/j.prerep.2026.100077","DOIUrl":"10.1016/j.prerep.2026.100077","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of neurodegenerative disorders is increasing globally, and although treatments exist, few are effective in slowing the rate of cognitive/functional decline associated with these conditions. The standardised <em>Ginkgo biloba</em> extract EGb-761 has been studied for possible neuroprotection, however the findings have varied significantly.</div></div><div><h3>Aim and Objective</h3><div>This systematic review and meta-analysis examined the cognitive, functional and behavioural effects of EGb-761 in adults suffering from Alzheimer's disease, vascular dementia or mild cognitive impairment and evaluated the strength of evidence.</div></div><div><h3>Methods</h3><div>PRISMA 2020 guidelines were followed for the preparation of this systematic review. The study was also registered at PROSPERO (CRD420251207465). Randomised and quasi-randomised controlled trials published between 2000 and 2025 were identified via a search of 5 major databases. A variety of cognitive, behavioural, and functional measures were analysed using standardised mean differences or mean differences with 95 % confidence intervals. The <em>I²</em> statistic was used to determine the level of heterogeneity between studies. All statistical analyses were completed using Review Manager 5.4.</div></div><div><h3>Results</h3><div>Eighteen studies representing 7558 participants were included in the final analysis, 10 of which provided sufficient data for inclusion in a meta-analysis. While there were statistically insignificant changes in cognitive function, the pooled SMD of ADAS Cog was 0.03 with a 95 % CI of −0.27–0.33, with high levels of heterogeneity (<em>I²</em> = 80 %). Similarly, the pooled MD of behavioural outcomes as measured by GERRI was 0.06 with a 95 % CI of −0.07–0.20, showing no statistically significant difference. The pooled SMD of functional outcomes as measured by ADL was 0.02 with a 95 % CI of −0.17–0.21, again showing no statistically significant difference, with low levels of heterogeneity (<em>I²</em> = 7 %).</div></div><div><h3>Conclusion</h3><div><em>Ginkgo biloba</em> extract had small and clinically meaningless effects on cognition, behaviour and functional ability. The quality of the evidence ranged from low to moderate, suggesting further large-scale, well-controlled studies are required to establish whether it may be useful in the treatment of neurodegenerative disorders.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037760","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 : 2026-06-01Epub Date: 2026-01-13DOI: 10.1016/j.prerep.2026.100075
Simran Gajanan Amonkar , Aditi Venkatesh Naik
Phytochemicals demonstrate broad anticancer potential and favourable safety profiles, yet their therapeutic value is limited by poor solubility, rapid metabolism, and low bioavailability. Nanocarrier-assisted delivery addresses these challenges by enhancing stability, prolonging circulation, and enabling tumour-selective release. Developments across polymeric, lipid-based, inorganic, protein-derived, and exosome-like systems have strengthened delivery performance through ligand-directed targeting, surface engineering, and stimuli-responsive designs. A bibliometric assessment of 117 peer-reviewed studies published between 2010 and 2025 reveals increasing research activity in encapsulation strategies, targeted delivery approaches, and translational nanomedicine, with major contributions from India, China, and the United States. Emerging innovations including AI-guided formulation methods, hybrid nanosystems, and multi-omics-based optimisation are advancing phytochemical therapeutics toward greater precision and clinical feasibility. The growing body of evidence supports the translational promise of phytochemical-loaded nanocarriers. Continued progress in scalable synthesis, regulatory alignment, and rigorous in vivo evaluation will be essential for establishing these platforms as next-generation cancer therapeutics.
{"title":"Nanocarrier-assisted phytochemical drug delivery in cancer therapy: A bibliometric analysis and integrative review of challenges, innovations, and translational potential","authors":"Simran Gajanan Amonkar , Aditi Venkatesh Naik","doi":"10.1016/j.prerep.2026.100075","DOIUrl":"10.1016/j.prerep.2026.100075","url":null,"abstract":"<div><div>Phytochemicals demonstrate broad anticancer potential and favourable safety profiles, yet their therapeutic value is limited by poor solubility, rapid metabolism, and low bioavailability. Nanocarrier-assisted delivery addresses these challenges by enhancing stability, prolonging circulation, and enabling tumour-selective release. Developments across polymeric, lipid-based, inorganic, protein-derived, and exosome-like systems have strengthened delivery performance through ligand-directed targeting, surface engineering, and stimuli-responsive designs. A bibliometric assessment of 117 peer-reviewed studies published between 2010 and 2025 reveals increasing research activity in encapsulation strategies, targeted delivery approaches, and translational nanomedicine, with major contributions from India, China, and the United States. Emerging innovations including AI-guided formulation methods, hybrid nanosystems, and multi-omics-based optimisation are advancing phytochemical therapeutics toward greater precision and clinical feasibility. The growing body of evidence supports the translational promise of phytochemical-loaded nanocarriers. Continued progress in scalable synthesis, regulatory alignment, and rigorous in vivo evaluation will be essential for establishing these platforms as next-generation cancer therapeutics.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978280","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 : 2026-06-01Epub Date: 2025-12-15DOI: 10.1016/j.prerep.2025.100073
Cletus Anes Ukwubile , Nnamdi David Menkiti , Ahamefula Anslem Ahuchaogu , Nathan Isaac Dibal , Blessing Ogechukwu Umeokoli
Ziziphus lotus (L.) Lam. is traditionally used in Nigeria for the treatment of renal and inflammatory disorders. Despite its ethnomedicinal importance, scientific evidence supporting its nephroprotective activity and underlying molecular mechanisms remains limited. This study aims to investigate the phytochemical composition, antioxidant potential, and nephroprotective effects of Z. lotus leaf extract against paracetamol-induced nephrotoxicity in rats, supported by molecular docking analysis. The methanol leaf extract of Z. lotus was fractionated by solvent partitioning, and the bioactive ethyl acetate fraction (EF) was analyzed using GC–MS NMR, and FTIR. Total phenolic and flavonoid contents were determined by colorimetric methods, while antioxidant activity was assessed by DPPH and ABTS assays. Nephroprotective effects were evaluated in rats by measuring serum urea, creatinine, uric acid, renal MDA, SOD, CAT, and GSH levels. Molecular docking predicted interactions between the identified compounds and protein targets associated with oxidative stress and renal injury. Phytochemical screening revealed alkaloids, flavonoids, tannins, triterpenoids, cardiac glycosides, and phytosterols. GC–MS identified 18 major constituents, and NMR elucidated five key compounds: phthalic acid monoethyl ester, methyl α-D-glucopyranoside, styracitol, pentadecanoic acid 14-methyl ester, and n-hexadecanoic acid. The extract exhibited strong antioxidant activity (DPPH IC₅₀ = 8.22 µg/mL; ABTS IC₅₀ = 12.08 µg/mL) and high phenolic content (408.12 mg GAE/g). Treatment with Z. lotus significantly restored renal biomarkers levels to normal, improved antioxidant enzyme levels, and provided histological evidence of renal protection. Molecular docking revealed that the five compounds showed high binding affinities (−7.2 to −9.1 kcal/mol) with key nephroprotective proteins. The polyphenolic and fatty acid constituents of Z. lotus contribute to its potent antioxidant and nephroprotective properties, providing scientific validation for its traditional use and potential for developing novel nephroprotective therapies.
{"title":"Protective effects of Ziziphus lotus Lam. leaf extract against paracetamol-induced nephrotoxicity in rats: Phytochemical profiling, antioxidant activity, and molecular docking analysis","authors":"Cletus Anes Ukwubile , Nnamdi David Menkiti , Ahamefula Anslem Ahuchaogu , Nathan Isaac Dibal , Blessing Ogechukwu Umeokoli","doi":"10.1016/j.prerep.2025.100073","DOIUrl":"10.1016/j.prerep.2025.100073","url":null,"abstract":"<div><div><em>Ziziphus lotus</em> (L.) Lam. is traditionally used in Nigeria for the treatment of renal and inflammatory disorders. Despite its ethnomedicinal importance, scientific evidence supporting its nephroprotective activity and underlying molecular mechanisms remains limited. This study aims to investigate the phytochemical composition, antioxidant potential, and nephroprotective effects of <em>Z. lotus</em> leaf extract against paracetamol-induced nephrotoxicity in rats, supported by molecular docking analysis. The methanol leaf extract of <em>Z. lotus</em> was fractionated by solvent partitioning, and the bioactive ethyl acetate fraction (EF) was analyzed using GC–MS NMR, and FTIR. Total phenolic and flavonoid contents were determined by colorimetric methods, while antioxidant activity was assessed by DPPH and ABTS assays. Nephroprotective effects were evaluated in rats by measuring serum urea, creatinine, uric acid, renal MDA, SOD, CAT, and GSH levels. Molecular docking predicted interactions between the identified compounds and protein targets associated with oxidative stress and renal injury. Phytochemical screening revealed alkaloids, flavonoids, tannins, triterpenoids, cardiac glycosides, and phytosterols. GC–MS identified 18 major constituents, and NMR elucidated five key compounds: phthalic acid monoethyl ester, methyl α-<span>D</span>-glucopyranoside, styracitol, pentadecanoic acid 14-methyl ester, and n-hexadecanoic acid. The extract exhibited strong antioxidant activity (DPPH IC₅₀ = 8.22 µg/mL; ABTS IC₅₀ = 12.08 µg/mL) and high phenolic content (408.12 mg GAE/g). Treatment with <em>Z. lotus</em> significantly restored renal biomarkers levels to normal, improved antioxidant enzyme levels, and provided histological evidence of renal protection. Molecular docking revealed that the five compounds showed high binding affinities (−7.2 to −9.1 kcal/mol) with key nephroprotective proteins. The polyphenolic and fatty acid constituents of <em>Z. lotus</em> contribute to its potent antioxidant and nephroprotective properties, providing scientific validation for its traditional use and potential for developing novel nephroprotective therapies.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765940","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 : 2026-06-01Epub Date: 2026-01-10DOI: 10.1016/j.prerep.2026.100074
Gobardhan Bal , Lakshmi Kanakaraj , Bibhash Chandra Mohanta
Purpose
In oral drug delivery system, food may influence the effectiveness of the drug by modulating its bioavailability. Understanding these interactions between food and drugs is crucial during drug development. However, the conventional approaches used to identify them are expensive and time-consuming clinical trials, which are often impractical. The objective of this study is to address these challenges by leveraging physiologically based pharmacokinetic(PBPK) models as efficient in-silico tools to predict food effects using significantly less time and resources.
Methods
This work focused on developing and validating PBPK models of two low solubility anticancer drugs, Alectinib and Acalabrutinib, utilizing minimal in-vitro characterization data available at the early stage of drug development to demonstrate successful prediction of food effect. The models were developed for healthy humans incorporating drug-specific physicochemical properties, in-vitro characterization data, and physiological parameters of the gastrointestinal tract under both fasted and fed conditions.
Results
The prediction accuracy of the developed models was validated against the observed clinical data and further used for virtual population simulation to predict the food effect. The model validation parameters met the 2-fold error limit criteria. The predicted food effect data revealed that, despite low solubility, Alectinib exhibited a significant positive food effect, while Acalabrutinib showed no clinically relevant impact, consistent with the observed clinical data.
Conclusion
This work underscores the significance of the in-silico modeling and simulation approach in predicting the food effect of orally administered drugs, which could be used to minimize or optimize time-extensive and cost-expensive clinical trials in drug development.
{"title":"Evaluation of food effects on two anticancer drugs in humans: Application of physiologically based pharmacokinetic modeling as a surrogate strategy to minimize In-Vivo studies in drug development","authors":"Gobardhan Bal , Lakshmi Kanakaraj , Bibhash Chandra Mohanta","doi":"10.1016/j.prerep.2026.100074","DOIUrl":"10.1016/j.prerep.2026.100074","url":null,"abstract":"<div><h3>Purpose</h3><div>In oral drug delivery system, food may influence the effectiveness of the drug by modulating its bioavailability. Understanding these interactions between food and drugs is crucial during drug development. However, the conventional approaches used to identify them are expensive and time-consuming clinical trials, which are often impractical. The objective of this study is to address these challenges by leveraging physiologically based pharmacokinetic(PBPK) models as efficient <em>in-silico</em> tools to predict food effects using significantly less time and resources.</div></div><div><h3>Methods</h3><div>This work focused on developing and validating PBPK models of two low solubility anticancer drugs, Alectinib and Acalabrutinib, utilizing minimal <em>in-vitro</em> characterization data available at the early stage of drug development to demonstrate successful prediction of food effect. The models were developed for healthy humans incorporating drug-specific physicochemical properties, <em>in-vitro</em> characterization data, and physiological parameters of the gastrointestinal tract under both fasted and fed conditions.</div></div><div><h3>Results</h3><div>The prediction accuracy of the developed models was validated against the observed clinical data and further used for virtual population simulation to predict the food effect. The model validation parameters met the 2-fold error limit criteria. The predicted food effect data revealed that, despite low solubility, Alectinib exhibited a significant positive food effect, while Acalabrutinib showed no clinically relevant impact, consistent with the observed clinical data.</div></div><div><h3>Conclusion</h3><div>This work underscores the significance of the <em>in-silico</em> modeling and simulation approach in predicting the food effect of orally administered drugs, which could be used to minimize or optimize time-extensive and cost-expensive clinical trials in drug development.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"5 ","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978278","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}
Osteoarthritis is a progressive chronic degenerative joint disease characterized by inflammation, pain, and articular cartilage deterioration. The current pharmacotherapies for osteoarthritis do not address the progression of osteoarthritis and are also associated with several adverse effects. Herbal medicines are emerging as potential source for the safe and effective treatment of osteoarthritis. Orthogrit, an herbo-mineral prescription medicine, has anti-oxidant, anti-inflammatory, and cartilage promoting properties that can potentially halt progression of osteoarthritis by its multifaceted bioactivities. The present study aimed to characterize the pharmacological effects of Orthogrit using 3D culture of human knee articular chondrocytes (NHAC-kn) and Caenorhabditis elegans. The chemical characterization of Orthogrit was performed by UHPLC analysis. The in vitro evaluation of Orthogrit was performed on TNF-α and IL-1β co-induced NHAC-kn spheroids; and in vivo analysis on LPS- exposed N2 (wild-type) strain of C. elegans. In chondrocytic spheroids, Orthogrit treatment reduced chondrotoxicity, ROS levels, and release of IL-6, PGE2, and CTXII, a marker of cartilage degradation. Treatment with Orthogrit normalized mitochondrial membrane potential; levels of aggrecan, and sulphated glycosaminoglycans; and reporter activity of IL-1β and NF-κB. In LPS-exposed C. elegans, Orthogrit treatment decreased nematode mortality, ROS levels and normalized locomotory behaviour (reversal and omega turns), SOD, Catalase and GSH levels. The mRNA expression analysis revealed that Orthogrit acts against progression of osteoarthritis by regulating inflammation mediators (JAK2, COX2), catabolic ECM enzymes (MMP1, MMP3, ADAMTS-4), redox homeostasis (Nrf2), p38 MAPK signalling (PMK-1, SEK-1) and apoptosis (CED-3). Taken together, Orthogrit is a potential therapeutic agent for management of osteoarthritis.
{"title":"In human knee articular chondrocytic-spheroids, Orthogrit modulates TNF-α and IL-1β induced inflammation, oxidative stress, ECM catabolism, and improves locomotory behaviour in Caenorhabditis elegans","authors":"Acharya Balkrishna , Vivek Gohel , Nishit Pathak , Meenu Tomer , Rishabh Dev , Anurag Varshney","doi":"10.1016/j.prerep.2025.100050","DOIUrl":"10.1016/j.prerep.2025.100050","url":null,"abstract":"<div><div>Osteoarthritis is a progressive chronic degenerative joint disease characterized by inflammation, pain, and articular cartilage deterioration. The current pharmacotherapies for osteoarthritis do not address the progression of osteoarthritis and are also associated with several adverse effects. Herbal medicines are emerging as potential source for the safe and effective treatment of osteoarthritis. Orthogrit, an herbo-mineral prescription medicine, has anti-oxidant, anti-inflammatory, and cartilage promoting properties that can potentially halt progression of osteoarthritis by its multifaceted bioactivities. The present study aimed to characterize the pharmacological effects of Orthogrit using 3D culture of human knee articular chondrocytes (NHAC-kn) and <em>Caenorhabditis elegans</em>. The chemical characterization of Orthogrit was performed by UHPLC analysis. The <em>in vitro</em> evaluation of Orthogrit was performed on TNF-α and IL-1β co-induced NHAC-kn spheroids; and <em>in vivo</em> analysis on LPS- exposed N2 (wild-type) strain of <em>C</em>. <em>elegans</em>. In chondrocytic spheroids, Orthogrit treatment reduced chondrotoxicity, ROS levels, and release of IL-6, PGE2, and CTXII, a marker of cartilage degradation. Treatment with Orthogrit normalized mitochondrial membrane potential; levels of aggrecan, and sulphated glycosaminoglycans; and reporter activity of IL-1β and NF-κB. In LPS-exposed <em>C</em>. <em>elegans</em>, Orthogrit treatment decreased nematode mortality, ROS levels and normalized locomotory behaviour (reversal and omega turns), SOD, Catalase and GSH levels. The mRNA expression analysis revealed that Orthogrit acts against progression of osteoarthritis by regulating inflammation mediators (<em>JAK2</em>, <em>COX2</em>), catabolic ECM enzymes (<em>MMP1</em>, <em>MMP3</em>, <em>ADAMTS-4</em>), redox homeostasis (<em>Nrf2</em>), p38 MAPK signalling (<em>PMK-1</em>, <em>SEK-1</em>) and apoptosis (<em>CED-3</em>). Taken together, Orthogrit is a potential therapeutic agent for management of osteoarthritis.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330607","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 : 2025-12-01Epub Date: 2025-11-21DOI: 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 : 2025-12-01Epub 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":"2025-12-01","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}
Pub Date : 2025-12-01Epub 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":"2025-12-01","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 : 2025-12-01Epub 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":"2025-12-01","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}
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