Ischemic stroke is a prominent cause of disability and mortality worldwide, currently no drug therapy is helpful for post-stroke symptoms; thus, there is a need to develop effective treatment strategies. Peptide medication development has advanced significantly in the recent years and due to its potential to modulate key molecular pathways involved in stroke pathophysiology. This review provides an overview of recent advances in peptide therapy for stroke. These peptides can exert neuroprotective effects by inhibiting excitotoxicity, oxidative stress, and apoptosis, while also promoting neuronal survival and synaptic plasticity. Furthermore, artificial intelligence (AI) with deep learning holds a promising technique in peptide generation by enabling the design of novel peptides with specific binding site of a protein, this may accelerate drug discovery processes through predictive modeling and high-throughput analysis. Overall, peptide therapy holds great potential for improving stroke outcomes and represents a promising avenue for the development of novel stroke treatments.
{"title":"Feasibility of recent peptide therapy for ischemic stroke: a comprehensive exploration","authors":"Kuo-Feng Tseng , Kuo-Wei Tseng , Hsien-Yin Liao , Pei-Hsien Chen","doi":"10.1016/j.jphs.2025.10.007","DOIUrl":"10.1016/j.jphs.2025.10.007","url":null,"abstract":"<div><div>Ischemic stroke is a prominent cause of disability and mortality worldwide, currently no drug therapy is helpful for post-stroke symptoms; thus, there is a need to develop effective treatment strategies. Peptide medication development has advanced significantly in the recent years and due to its potential to modulate key molecular pathways involved in stroke pathophysiology. This review provides an overview of recent advances in peptide therapy for stroke. These peptides can exert neuroprotective effects by inhibiting excitotoxicity, oxidative stress, and apoptosis, while also promoting neuronal survival and synaptic plasticity. Furthermore, artificial intelligence (AI) with deep learning holds a promising technique in peptide generation by enabling the design of novel peptides with specific binding site of a protein, this may accelerate drug discovery processes through predictive modeling and high-throughput analysis. Overall, peptide therapy holds great potential for improving stroke outcomes and represents a promising avenue for the development of novel stroke treatments.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"160 1","pages":"Pages 1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145435317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Microglia exhibit phenotypic plasticity between anti-inflammatory M2 and pro-inflammatory M1 states, and the transition from M2 to M1 is implicated in the progression of acute brain injuries. However, the molecular mechanisms that regulate this phenotypic shift remain poorly understood. Zn2+, stored in presynaptic vesicles, is extracellularly released during pathological events, such as cerebral ischemia, and modulates microglial function. In this study, we aimed to investigate the role of extracellular Zn2+ in the M2-to-M1 transition using BV2 microglial cells. Pretreatment with ZnCl2 during M2 polarization significantly suppressed lipopolysaccharide-induced production of interleukin (IL)-6 and tumor necrosis factor-α following the phenotypic shift. Among the zinc transporters, Zrt- and Irt-related protein 12 (ZIP12) expression was markedly upregulated by IL-4 stimulation, and siRNA-mediated knockdown of ZIP12 abolished the Zn2+-mediated suppression of pro-inflammatory cytokine production. Furthermore, ZIP12 knockdown reduced intracellular Zn2+ accumulation in IL-4-treated microglia, as revealed by FluoZin-3 fluorescence. These findings indicate that extracellular Zn2+ is taken up via ZIP12 during M2 polarization and subsequently acts to suppress pro-inflammatory cytokine production, thereby restraining the shift toward an M1 phenotype.
{"title":"Extracellular zinc suppresses microglial inflammatory shift via Zrt- and Irt-related protein 12-dependent uptake","authors":"Takaaki Aratake , Youichirou Higashi , Takahiro Shimizu , Satoshi Fukata , Motoaki Saito","doi":"10.1016/j.jphs.2025.10.006","DOIUrl":"10.1016/j.jphs.2025.10.006","url":null,"abstract":"<div><div>Microglia exhibit phenotypic plasticity between anti-inflammatory M2 and pro-inflammatory M1 states, and the transition from M2 to M1 is implicated in the progression of acute brain injuries. However, the molecular mechanisms that regulate this phenotypic shift remain poorly understood. Zn<sup>2+</sup>, stored in presynaptic vesicles, is extracellularly released during pathological events, such as cerebral ischemia, and modulates microglial function. In this study, we aimed to investigate the role of extracellular Zn<sup>2+</sup> in the M2-to-M1 transition using BV2 microglial cells. Pretreatment with ZnCl<sub>2</sub> during M2 polarization significantly suppressed lipopolysaccharide-induced production of interleukin (IL)-6 and tumor necrosis factor-α following the phenotypic shift. Among the zinc transporters, Zrt- and Irt-related protein 12 (ZIP12) expression was markedly upregulated by IL-4 stimulation, and siRNA-mediated knockdown of ZIP12 abolished the Zn<sup>2+</sup>-mediated suppression of pro-inflammatory cytokine production. Furthermore, ZIP12 knockdown reduced intracellular Zn<sup>2+</sup> accumulation in IL-4-treated microglia, as revealed by FluoZin-3 fluorescence. These findings indicate that extracellular Zn<sup>2+</sup> is taken up via ZIP12 during M2 polarization and subsequently acts to suppress pro-inflammatory cytokine production, thereby restraining the shift toward an M1 phenotype.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"160 1","pages":"Pages 29-36"},"PeriodicalIF":2.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal.
{"title":"TEMPORARY REMOVAL: Development and application of a method for quantitative monitoring of Isepamicin plasma concentration in human plasma based on liquid chromatography-mass spectrometry.","authors":"Lili Cui, Yanru Liu, Zhipeng Wang, Jingxue Liu, Shouhong Gao, Yi Shan, Xia Tao, Deduo Xu","doi":"10.1016/j.jphs.2025.10.003","DOIUrl":"https://doi.org/10.1016/j.jphs.2025.10.003","url":null,"abstract":"<p><p>The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal.</p>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Impaired neutrophil function is thought to increase infection risk associated with smoking. We examined the effects of nicotine- and tar-free cigarette smoke extracts (CSEs) from combustible cigarettes (CCs) and heated tobacco products (HTPs) on neutrophil-like HL-60 cells. HTP-derived CSEs exhibited lower cytotoxicity and milder impairment of neutrophil functions, including chemotaxis, reactive oxygen species production, phagocytosis, and neutrophil extracellular trap formation, than those of CC-derived CSEs. However, at higher concentrations, HTP-derived CSEs markedly impaired the cell viability and function. These results indicate that HTP emissions impair neutrophil functions at high concentrations, highlighting the need for cautious health risk evaluation.
{"title":"Effects of nicotine- and tar-free smoke extracts from combustible cigarettes and heated tobacco products on the function of neutrophil-like HL-60 cells","authors":"Yuichi Mazaki , Soichi Miwa , Ryosuke Shinkai , Takahiro Horinouchi","doi":"10.1016/j.jphs.2025.10.004","DOIUrl":"10.1016/j.jphs.2025.10.004","url":null,"abstract":"<div><div>Impaired neutrophil function is thought to increase infection risk associated with smoking. We examined the effects of nicotine- and tar-free cigarette smoke extracts (CSEs) from combustible cigarettes (CCs) and heated tobacco products (HTPs) on neutrophil-like HL-60 cells. HTP-derived CSEs exhibited lower cytotoxicity and milder impairment of neutrophil functions, including chemotaxis, reactive oxygen species production, phagocytosis, and neutrophil extracellular trap formation, than those of CC-derived CSEs. However, at higher concentrations, HTP-derived CSEs markedly impaired the cell viability and function. These results indicate that HTP emissions impair neutrophil functions at high concentrations, highlighting the need for cautious health risk evaluation.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 322-326"},"PeriodicalIF":2.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-17DOI: 10.1016/j.jphs.2025.10.002
Jianwen Zhang , Qiuwei Hua , Lun Gao , Shangwen Yang , Minghui Lu , Qiang Cai
Intracerebral hemorrhage is the second most common subtype of stroke, characterized by high mortality and disability rates. To date, the mechanism of brain injury caused by intracerebral hemorrhage remains unclear, and there are no effective treatments to delay the progression of brain injury after intracerebral hemorrhage. Increasing evidence suggests that oxidative stress plays a crucial role in secondary injury induced by intracerebral hemorrhage, and ferroptosis plays a dominant role in the pathogenesis of brain injury after intracerebral hemorrhage.
In this study, we demonstrated in an in vitro hemin-induced PC12 cell model that astaxanthin improved cell viability, inhibited oxidative stress after intracerebral hemorrhage, and suppressed ferroptosis by upregulating the expression of glutathione peroxidase 4 and solute carrier family 7a member 11. In an in vivo autologous blood injection intracerebral hemorrhage rat model, we confirmed that astaxanthin could resist oxidative stress, ferroptosis, and further inflammatory responses by upregulating the expression of glutathione peroxidase 4 and solute carrier family 7a member 11 through the Akt1-FoxO3a pathway to protect against brain injury after intracerebral hemorrhage.
{"title":"Astaxanthin suppress ferroptosis through the Akt1-FoxO3a signaling pathway to alleviates brain injury after intracerebral hemorrhage","authors":"Jianwen Zhang , Qiuwei Hua , Lun Gao , Shangwen Yang , Minghui Lu , Qiang Cai","doi":"10.1016/j.jphs.2025.10.002","DOIUrl":"10.1016/j.jphs.2025.10.002","url":null,"abstract":"<div><div>Intracerebral hemorrhage is the second most common subtype of stroke, characterized by high mortality and disability rates. To date, the mechanism of brain injury caused by intracerebral hemorrhage remains unclear, and there are no effective treatments to delay the progression of brain injury after intracerebral hemorrhage. Increasing evidence suggests that oxidative stress plays a crucial role in secondary injury induced by intracerebral hemorrhage, and ferroptosis plays a dominant role in the pathogenesis of brain injury after intracerebral hemorrhage.</div><div>In this study, we demonstrated in an in vitro hemin-induced PC12 cell model that astaxanthin improved cell viability, inhibited oxidative stress after intracerebral hemorrhage, and suppressed ferroptosis by upregulating the expression of glutathione peroxidase 4 and solute carrier family 7a member 11. In an in vivo autologous blood injection intracerebral hemorrhage rat model, we confirmed that astaxanthin could resist oxidative stress, ferroptosis, and further inflammatory responses by upregulating the expression of glutathione peroxidase 4 and solute carrier family 7a member 11 through the Akt1-FoxO3a pathway to protect against brain injury after intracerebral hemorrhage.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 310-321"},"PeriodicalIF":2.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145417128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Imeglimin, a novel oral antidiabetic drug, has been suggested to affect mitochondrial functions in some types of cells and tissues, however, it has never been investigated whether aging has an impact on its pharmacological effects in the brain. In this study, we investigated whether imeglimin directly affects functions of brain mitochondria and whether its intraperitoneal injection protects against ischemic brain injury in young, middle-aged and aged Wistar rats. We found that direct addition of imeglimin to mitochondria isolated from young and middle-aged rat brains suppressed oxidative phosphorylation and activities of mitochondrial Complexes I and IV. The opposite, stimulating effect on Complex II activity was observed within the same groups. Injection of imeglimin 24 h before simulated brain ischemia in vitro reduced infarct size only in young and middle-aged rat groups. In the aged rat group, imeglimin did not reduce cerebral infarct size nor directly modulate mitochondrial respiration and activities of the complexes. In conclusion, we provided novel evidence on potential effects of imeglimin in the brain by demonstrating a direct stimulating effect on mitochondrial Complex II activity and age-dependent protective effects against brain injury under in vitro simulated ischemia.
{"title":"Effects of imeglimin on mitochondrial functions and ischemic brain damage in young and aging rats","authors":"Evelina Paskeviciene, Kristina Skemiene, Katryna Pampuscenko, Silvija Jankeviciute, Vilmante Borutaite","doi":"10.1016/j.jphs.2025.10.001","DOIUrl":"10.1016/j.jphs.2025.10.001","url":null,"abstract":"<div><div>Imeglimin, a novel oral antidiabetic drug, has been suggested to affect mitochondrial functions in some types of cells and tissues, however, it has never been investigated whether aging has an impact on its pharmacological effects in the brain. In this study, we investigated whether imeglimin directly affects functions of brain mitochondria and whether its intraperitoneal injection protects against ischemic brain injury in young, middle-aged and aged Wistar rats. We found that direct addition of imeglimin to mitochondria isolated from young and middle-aged rat brains suppressed oxidative phosphorylation and activities of mitochondrial Complexes I and IV. The opposite, stimulating effect on Complex II activity was observed within the same groups. Injection of imeglimin 24 h before simulated brain ischemia <em>in vitro</em> reduced infarct size only in young and middle-aged rat groups. In the aged rat group, imeglimin did not reduce cerebral infarct size nor directly modulate mitochondrial respiration and activities of the complexes. In conclusion, we provided novel evidence on potential effects of imeglimin in the brain by demonstrating a direct stimulating effect on mitochondrial Complex II activity and age-dependent protective effects against brain injury under <em>in vitro</em> simulated ischemia.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 301-309"},"PeriodicalIF":2.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose-limiting toxicity with limited countermeasures. Basic research has revealed that omeprazole, a proton pump inhibitor (PPI), exerts preventive effects against OIPN. In this study, we evaluated whether other PPIs exert similar effects via in vitro and in vivo experiments. Notably, esomeprazole, lansoprazole, and rabeprazole, classified as PPIs, prevented oxaliplatin-induced cultured F11 neuronal cell damage, and repeated PPI administration prevented mechanical allodynia in rats. However, vonoprazan, a potassium ion-competitive acid blocker, did not exert such effects. Overall, our results highlight the class effects of PPIs against OIPN.
{"title":"Class effects of proton pump inhibitors in preventing oxaliplatin-induced peripheral neurotoxicity","authors":"Yusuke Mori , Keisuke Mine , Takehiro Kawashiri , Yusuke Koura , Mami Ueda , Risa Kaneko , Shunsuke Fujita , Akito Tsuruta , Satoru Koyanagi , Daisuke Kobayashi","doi":"10.1016/j.jphs.2025.09.010","DOIUrl":"10.1016/j.jphs.2025.09.010","url":null,"abstract":"<div><div>Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose-limiting toxicity with limited countermeasures. Basic research has revealed that omeprazole, a proton pump inhibitor (PPI), exerts preventive effects against OIPN. In this study, we evaluated whether other PPIs exert similar effects via <em>in vitro</em> and <em>in vivo</em> experiments. Notably, esomeprazole, lansoprazole, and rabeprazole, classified as PPIs, prevented oxaliplatin-induced cultured F11 neuronal cell damage, and repeated PPI administration prevented mechanical allodynia in rats. However, vonoprazan, a potassium ion-competitive acid blocker, did not exert such effects. Overall, our results highlight the class effects of PPIs against OIPN.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 279-282"},"PeriodicalIF":2.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duchenne muscular dystrophy (DMD) is a severe X-linked genetic disorder caused by mutations in the dystrophin gene. Although the C57BL/10 background mdx mouse (B10-mdx) model is widely used for DMD research, it presents milder symptoms than observed in human patients. In contrast, the DBA/2N-mdx model exhibits more severe pathology, making it a promising model for evaluating disease mechanisms and therapies. In this study, we employed a 24-h behavioral monitoring system to investigate spontaneous locomotor activity and gait characteristics in DBA/2N-mdx mice. We observed significantly reduced movement and shorter active periods during the dark (active) phase at 4 and 8 weeks of age in DBA/2N-mdx mice compared to controls. Subsequent gait analysis revealed shorter walking distances, slower speeds, and reduced body extension during straight walking. These findings suggest that the DBA/2N-mdx mouse model exhibits distinct behavioral abnormalities that parallel DMD symptoms in humans. Our noninvasive, continuous monitoring approach provides an innovative method for assessing motor impairments and may facilitate more accurate preclinical assessments of potential therapies for DMD.
{"title":"Uncovering motor impairments in duchenne muscular dystrophy: 24-hour automated behavioral analysis of DBA/2N-mdx mice","authors":"Misato Kida , Yui Kobayashi , Takamasa Numano , Masahiko Yasuda , Seinosuke Sakai , Takashi Minato , Takuya Kishi , Masahiro Fukuda , Keisuke Omori , Taichi Yamamoto , Takahisa Murata","doi":"10.1016/j.jphs.2025.09.011","DOIUrl":"10.1016/j.jphs.2025.09.011","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a severe X-linked genetic disorder caused by mutations in the dystrophin gene. Although the C57BL/10 background mdx mouse (B10-mdx) model is widely used for DMD research, it presents milder symptoms than observed in human patients. In contrast, the DBA/2N-mdx model exhibits more severe pathology, making it a promising model for evaluating disease mechanisms and therapies. In this study, we employed a 24-h behavioral monitoring system to investigate spontaneous locomotor activity and gait characteristics in DBA/2N-mdx mice. We observed significantly reduced movement and shorter active periods during the dark (active) phase at 4 and 8 weeks of age in DBA/2N-mdx mice compared to controls. Subsequent gait analysis revealed shorter walking distances, slower speeds, and reduced body extension during straight walking. These findings suggest that the DBA/2N-mdx mouse model exhibits distinct behavioral abnormalities that parallel DMD symptoms in humans. Our noninvasive, continuous monitoring approach provides an innovative method for assessing motor impairments and may facilitate more accurate preclinical assessments of potential therapies for DMD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 283-291"},"PeriodicalIF":2.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-25DOI: 10.1016/j.jphs.2025.09.009
Li-King Yang , Leticia B. Sy , Ju-Fang Liu , Tsung-Ming Chang , Ji-Fan Lin , Chi-Jen Chang
Cisplatin is a commonly used chemotherapy drug that can effectively treat a variety of cancers, but it often causes severe side effects, including nephrotoxicity, ototoxicity, and gastrointestinal toxicity, which significantly affects patients' quality of life. Lutein is a natural carotenoid known for its potent antioxidant properties. Recent literature supports the beneficial effects of lutein supplements in conditions such as retinal degeneration, cardiovascular disease, and liver damage, emphasizing its broad anti-inflammatory capabilities. However, the mechanism by which cisplatin causes intestinal inflammation and the protective effect of lutein against this remain unknown. Here, we investigated the potential protective effect of lutein against cisplatin-induced intestinal epithelial injury. Our results proved that cisplatin significantly decreased cell viability, enhanced ROS generation, and activated inflammatory signaling pathways involving p38, ERK, and NF-κB in IEC-6 cells. Pretreatment with lutein markedly suppressed ROS production, reduced p38 and ERK phosphorylation, prevented NF-κB activation, and consequently attenuated inflammatory cytokine expression. These findings establish lutein as a promising dietary strategy to reduce cisplatin-induced intestinal inflammation, supporting its therapeutic potential for improving chemotherapy tolerance.
{"title":"Lutein reduces cisplatin-induced intestinal inflammation by inhibiting ROS-mediated MAPK/NF-κB pathways","authors":"Li-King Yang , Leticia B. Sy , Ju-Fang Liu , Tsung-Ming Chang , Ji-Fan Lin , Chi-Jen Chang","doi":"10.1016/j.jphs.2025.09.009","DOIUrl":"10.1016/j.jphs.2025.09.009","url":null,"abstract":"<div><div>Cisplatin is a commonly used chemotherapy drug that can effectively treat a variety of cancers, but it often causes severe side effects, including nephrotoxicity, ototoxicity, and gastrointestinal toxicity, which significantly affects patients' quality of life. Lutein is a natural carotenoid known for its potent antioxidant properties. Recent literature supports the beneficial effects of lutein supplements in conditions such as retinal degeneration, cardiovascular disease, and liver damage, emphasizing its broad anti-inflammatory capabilities. However, the mechanism by which cisplatin causes intestinal inflammation and the protective effect of lutein against this remain unknown. Here, we investigated the potential protective effect of lutein against cisplatin-induced intestinal epithelial injury. Our results proved that cisplatin significantly decreased cell viability, enhanced ROS generation, and activated inflammatory signaling pathways involving p38, ERK, and NF-κB in IEC-6 cells. Pretreatment with lutein markedly suppressed ROS production, reduced p38 and ERK phosphorylation, prevented NF-κB activation, and consequently attenuated inflammatory cytokine expression. These findings establish lutein as a promising dietary strategy to reduce cisplatin-induced intestinal inflammation, supporting its therapeutic potential for improving chemotherapy tolerance.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 292-300"},"PeriodicalIF":2.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145269340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-20DOI: 10.1016/j.jphs.2025.09.008
Jun Horizono , Keito Mizumoto , Mary Ann Suico , Shota Kaseda , Yuya Sannomiya , Haruki Tsuhako , Aimi Owaki , Ryoichi Sato , Masahiro Shiraga , Riko Kato , Ryo Kumabe , Tsuyoshi Shuto , Hirofumi Kai
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and angiotensin receptor blockers (ARBs) each have renoprotective effects in chronic kidney diseases, including Alport syndrome. Here, we investigated the combination of SGLT2i dapagliflozin and ARBs with different antiproteinuric strength - losartan (weak) and olmesartan (strong) - in Col4a5 G5X Alport mice. Dapagliflozin enhanced the renoprotective effect of losartan but not of olmesartan. Olmesartan alone suppressed the decline in renal function and prolonged survival similarly to losartan plus dapagliflozin. These findings suggest that the add-on effectiveness of dapagliflozin varies depending on the ARB, and that their combination needs careful evaluation for maximum benefit.
{"title":"Dapagliflozin with losartan but not olmesartan has an add-on protective effect in experimental Alport syndrome","authors":"Jun Horizono , Keito Mizumoto , Mary Ann Suico , Shota Kaseda , Yuya Sannomiya , Haruki Tsuhako , Aimi Owaki , Ryoichi Sato , Masahiro Shiraga , Riko Kato , Ryo Kumabe , Tsuyoshi Shuto , Hirofumi Kai","doi":"10.1016/j.jphs.2025.09.008","DOIUrl":"10.1016/j.jphs.2025.09.008","url":null,"abstract":"<div><div>Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and angiotensin receptor blockers (ARBs) each have renoprotective effects in chronic kidney diseases, including Alport syndrome. Here, we investigated the combination of SGLT2i dapagliflozin and ARBs with different antiproteinuric strength - losartan (weak) and olmesartan (strong) - in <em>Col4a5</em> G5X Alport mice. Dapagliflozin enhanced the renoprotective effect of losartan but not of olmesartan. Olmesartan alone suppressed the decline in renal function and prolonged survival similarly to losartan plus dapagliflozin. These findings suggest that the add-on effectiveness of dapagliflozin varies depending on the ARB, and that their combination needs careful evaluation for maximum benefit.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 252-255"},"PeriodicalIF":2.9,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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