Journal of pharmacological sciences最新文献_第4页

Astaxanthin suppress ferroptosis through the Akt1-FoxO3a signaling pathway to alleviates brain injury after intracerebral hemorrhage 虾青素通过Akt1-FoxO3a信号通路抑制铁下垂，减轻脑出血后脑损伤

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-10-17 DOI: 10.1016/j.jphs.2025.10.002

Jianwen Zhang , Qiuwei Hua , Lun Gao , Shangwen Yang , Minghui Lu , Qiang Cai

{"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":"2025-12-01","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}

引用次数: 0

Effects of nicotine- and tar-free smoke extracts from combustible cigarettes and heated tobacco products on the function of neutrophil-like HL-60 cells 可燃香烟和加热烟草制品中不含尼古丁和焦油的烟雾提取物对嗜中性粒细胞样HL-60细胞功能的影响

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-10-27 DOI: 10.1016/j.jphs.2025.10.004

Yuichi Mazaki , Soichi Miwa , Ryosuke Shinkai , Takahiro Horinouchi

引用次数: 0

Class effects of proton pump inhibitors in preventing oxaliplatin-induced peripheral neurotoxicity 质子泵抑制剂在预防奥沙利铂诱导的周围神经毒性中的一类作用

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-09-29 DOI: 10.1016/j.jphs.2025.09.010

Yusuke Mori , Keisuke Mine , Takehiro Kawashiri , Yusuke Koura , Mami Ueda , Risa Kaneko , Shunsuke Fujita , Akito Tsuruta , Satoru Koyanagi , Daisuke Kobayashi

引用次数: 0

Lutein reduces cisplatin-induced intestinal inflammation by inhibiting ROS-mediated MAPK/NF-κB pathways 叶黄素通过抑制ros介导的MAPK/NF-κB通路减少顺铂诱导的肠道炎症

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-09-25 DOI: 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

{"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":"2025-12-01","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}

引用次数: 0

Uncovering motor impairments in duchenne muscular dystrophy: 24-hour automated behavioral analysis of DBA/2N-mdx mice 揭示杜氏肌营养不良症的运动损伤：DBA/2N-mdx小鼠的24小时自动行为分析

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-09-29 DOI: 10.1016/j.jphs.2025.09.011

Misato Kida , Yui Kobayashi , Takamasa Numano , Masahiko Yasuda , Seinosuke Sakai , Takashi Minato , Takuya Kishi , Masahiro Fukuda , Keisuke Omori , Taichi Yamamoto , Takahisa Murata

{"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":"2025-12-01","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}

引用次数: 0

Rho kinase 2 promotes epithelial-mesenchymal transition and proliferation in human prostate cancer PC-3 cells Rho激酶2促进人前列腺癌PC-3细胞上皮间质转化和增殖

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-09-20 DOI: 10.1016/j.jphs.2025.09.007

Alamgir Hossain , Aya Yamamura , Md Junayed Nayeem , Sivasundaram Karnan , Rie Takahashi , Hisaki Hayashi , Motohiko Sato

{"title":"Rho kinase 2 promotes epithelial-mesenchymal transition and proliferation in human prostate cancer PC-3 cells","authors":"Alamgir Hossain , Aya Yamamura , Md Junayed Nayeem , Sivasundaram Karnan , Rie Takahashi , Hisaki Hayashi , Motohiko Sato","doi":"10.1016/j.jphs.2025.09.007","DOIUrl":"10.1016/j.jphs.2025.09.007","url":null,"abstract":"<div><div>Prostate cancer is the second most common cancer in men. Although androgen deprivation therapy is initially effective, resistance inevitably develops. Most patients eventually progress to castration-resistant prostate cancer, a stage with limited treatment options and poor prognosis. Rho kinases (ROCK1 and ROCK2) have been implicated in cancer progression, but their therapeutic targeting remains limited. This study examined the pathological roles of ROCK1 and ROCK2 in epithelial-mesenchymal transition (EMT) and proliferation of prostate cancer cells. ROCK1 expression was comparable between human prostate epithelial cells (PrECs) and androgen-independent prostate cancer cells, PC-3 and DU145. In contrast, ROCK2 expression was higher in PC-3 cells than in PrECs and DU145 cells. EMT marker analysis revealed that PC-3 cells exhibited decreased E-cadherin and increased N-cadherin and Snail expression. ROCK2 knockdown reversed this EMT phenotype, reducing cell proliferation, migration, 3D tumor spheroid formation, and spheroid cell viability. Similar inhibitory effects were observed by the ROCK2-selective blocker KD025 (IC<sub>50</sub> = 422 nM). Furthermore, ROCK2 deficiency attenuated the tumor growth of PC-3 cells in a xenograft mouse model. These findings indicate that ROCK2 promotes EMT process and tumor progression in PC-3 cells. Targeting ROCK2 may represent a promising therapeutic strategy for androgen-independent prostate cancer.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 229-241"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108613","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}

引用次数: 0

Rosiridin reduces Idiopathic Pulmonary Fibrosis by inhibiting the STAT3/NFκB/SMAD3 signaling pathways 罗西瑞定通过抑制STAT3/NFκB/SMAD3信号通路减少特发性肺纤维化

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-09-19 DOI: 10.1016/j.jphs.2025.09.004

Yuyao Li , Huili Qi , Haoyue Xu , Xuehai Jia , Wenyan Chen , Ruoliu Pan , Xinhui Pan , Hangyu Wang , Dahong Yao , Ke Zhang , Jinhui Wang

{"title":"Rosiridin reduces Idiopathic Pulmonary Fibrosis by inhibiting the STAT3/NFκB/SMAD3 signaling pathways","authors":"Yuyao Li , Huili Qi , Haoyue Xu , Xuehai Jia , Wenyan Chen , Ruoliu Pan , Xinhui Pan , Hangyu Wang , Dahong Yao , Ke Zhang , Jinhui Wang","doi":"10.1016/j.jphs.2025.09.004","DOIUrl":"10.1016/j.jphs.2025.09.004","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis is a progressive, highly lethal disease with limited treatment options. It is characterized by fibroblast-to-myofibroblast transformation, excessive ECM proliferation and collagen deposition, leading to the destruction of normal lung architecture and function. As a constituent of <em>Rhodiola rosea</em> L., rosiridin is a monomer with significant structural compatibility, conferring strong therapeutic potential. This bioactive compound mitigates oxidative stress-driven pathology and reverses its resultant damage in various diseases. However, its potential protective effects against bleomycin-induced IPF and the underlying mechanisms remain unclear. This study aimed to investigate the role and mechanism of rosiridin in IPF. Rosiridin attenuated TGF-β1-induced oxidative stress and inflammatory responses in lung epithelial cells and suppressed apoptosis associated with pulmonary fibrosis. Hematoxylin and eosin (HE) staining and Masson's trichrome staining showed that rosiridin improved pathological lung changes, reduced oxidative stress, and alleviated pulmonary fibrosis in a dose-dependent manner. Transcriptomic analysis revealed that rosiridin inhibited JAK protein activation, reduced the transformation of fibroblasts into myofibroblasts, and suppressed the secretion of proinflammatory and profibrotic cytokines. These findings suggest that rosiridin mitigates pulmonary fibrosis through modulation of the STAT3/NF-κB/SMAD3 signaling pathways. Rosiridin may represent a promising therapeutic candidate for the treatment of IPF.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 242-251"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108614","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}

引用次数: 0

Establishing a nanoluciferase-based assay as a high-throughput screening platform for therapeutics in congenital nephrotic syndrome 建立一种基于纳米荧光素的检测方法，作为先天性肾病综合征治疗方法的高通量筛选平台

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-09-20 DOI: 10.1016/j.jphs.2025.09.006

Haruki Tsuhako , Mary Ann Suico , Haruka Kojima , Saki Takahashi , Shunsuke Tanigawa , Misato Kamura , Ryoichi Sato , Riko Kato , Aimi Owaki , Ryuichi Nishinakamura , Tsuyoshi Shuto , Hirofumi Kai

{"title":"Establishing a nanoluciferase-based assay as a high-throughput screening platform for therapeutics in congenital nephrotic syndrome","authors":"Haruki Tsuhako , Mary Ann Suico , Haruka Kojima , Saki Takahashi , Shunsuke Tanigawa , Misato Kamura , Ryoichi Sato , Riko Kato , Aimi Owaki , Ryuichi Nishinakamura , Tsuyoshi Shuto , Hirofumi Kai","doi":"10.1016/j.jphs.2025.09.006","DOIUrl":"10.1016/j.jphs.2025.09.006","url":null,"abstract":"<div><div>Nephrin is crucial for the formation of the glomerular slit diaphragm, which is the final filtration barrier in the kidney. A mutation in the <em>NPHS1</em> gene that codes for nephrin causes congenital nephrotic syndrome of the Finnish type (CNF). Most missense mutations render nephrin non-functional due to the defective nephrin trafficking to the cell membrane. Pharmacological approaches that induce the expression of nephrin on the cell membrane are feasible, but therapeutic development is hampered by the lack of a high-throughput screening (HTS) system. Here, we developed a nanoluciferase HiBiT-based HTS platform to quantify the cell membrane expression of a nephrin mutant. This evaluation system reflected the previously reported results of various nephrin mutant localization. Using this system, we screened and identified 10 compounds that promoted the expression of the nephrin E725D mutant on the cell membrane. Moreover, the phosphorylation and N-glycosylation of nephrin, which are modifications that indicate its cell surface localization, correlated with the luminescence values of HiBiT-Nephrin in the compound screening. Consequently, this HiBiT-Nephrin evaluation system could be a new platform for predicting the pathogenicity of variants and searching for therapeutic agents for CNF.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 219-228"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108615","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}

引用次数: 0

Histone deacetylase inhibitors suppress retinal angiogenesis by preventing endothelial cell proliferation and accelerating VEGF degradation 组蛋白去乙酰化酶抑制剂通过阻止内皮细胞增殖和加速VEGF降解抑制视网膜血管生成

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-12-01 Epub Date: 2025-09-17 DOI: 10.1016/j.jphs.2025.09.005

Akane Morita, Kanako Takahashi, Naoto Iizuka, Tsutomu Nakahara

{"title":"Histone deacetylase inhibitors suppress retinal angiogenesis by preventing endothelial cell proliferation and accelerating VEGF degradation","authors":"Akane Morita, Kanako Takahashi, Naoto Iizuka, Tsutomu Nakahara","doi":"10.1016/j.jphs.2025.09.005","DOIUrl":"10.1016/j.jphs.2025.09.005","url":null,"abstract":"<div><div>Inhibitors of histone deacetylases (HDACs) suppress retinal angiogenesis by interrupting the vascular endothelial growth factor (VEGF)-mammalian target of rapamycin complex 1 (mTORC1) pathway in proliferating endothelial cells. To investigate the underlying mechanisms, we examined the effects of valproic acid (VPA) and vorinostat on the distribution of VEGF protein and phosphorylated S6 protein, an indicator of mTORC1 activity, in the neonatal mouse retina, an experimental model of retinal angiogenesis. Newborn mice were subcutaneously injected with VPA, vorinostat, or vehicle once daily from postnatal day (P) 0 to P3. Their eyes were collected at P4. Compared to vehicle-treated mice, retinal vascularization was delayed, and the number of proliferating vascular cells was reduced in front of the retinal vasculature in VPA- and vorinostat-treated mice. In P4 mice, a single injection of VPA or vorinostat reduced VEGF expression on the retinal surface at 2 and 6 h after injection. Both drugs reduced mTORC1 activity in proliferating endothelial cells. The proteasome inhibitor, MG132, suppressed the VPA- and vorinostat-induced reduction in VEGF expression on the retinal surface. These results suggest that HDAC inhibitors suppress retinal angiogenesis by preventing endothelial cell proliferation and accelerating VEGF protein degradation in a proteasome-dependent manner.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"159 4","pages":"Pages 268-278"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120569","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}

引用次数: 0

Aprepitant attenuates cutaneous mast cell migration in oxaliplatin-treated mice 阿瑞吡坦减轻奥沙利铂治疗小鼠皮肤肥大细胞的迁移

IF 2.9 3区医学

Journal of pharmacological sciences Pub Date : 2025-11-01 Epub Date: 2025-08-25 DOI: 10.1016/j.jphs.2025.08.008

Tsugunobu Andoh

引用次数: 0