Journal of pharmacological sciences最新文献_第10页

Imeglimin profoundly affects the circadian clock in mouse embryonic fibroblasts 依米明深刻影响小鼠胚胎成纤维细胞的生物钟

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-10-13 DOI: 10.1016/j.jphs.2023.10.001

Kotomi Miura , Jun-ichi Morishige , Jotaro Abe , Pingping Xu , Yifan Shi , Zheng Jing , Naoto Nagata , Ryo Miyazaki , Naoki Sakane , Michihiro Mieda , Masanori Ono , Yoshiko Maida , Tomoko Fujiwara , Hiroshi Fujiwara , Hitoshi Ando

{"title":"Imeglimin profoundly affects the circadian clock in mouse embryonic fibroblasts","authors":"Kotomi Miura , Jun-ichi Morishige , Jotaro Abe , Pingping Xu , Yifan Shi , Zheng Jing , Naoto Nagata , Ryo Miyazaki , Naoki Sakane , Michihiro Mieda , Masanori Ono , Yoshiko Maida , Tomoko Fujiwara , Hiroshi Fujiwara , Hitoshi Ando","doi":"10.1016/j.jphs.2023.10.001","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.10.001","url":null,"abstract":"<div><h3>Objective</h3><p>Imeglimin is a novel antidiabetic drug structurally related to metformin. Metformin has been shown to modulate the circadian clock in rat fibroblasts. Accordingly, in the present study, we aimed to determine whether imeglimin can impact the circadian oscillator in mouse embryonic fibroblasts (MEFs).</p></div><div><h3>Methods</h3><p>MEFs carrying a <em>Bmal1</em>-Emerald luciferase (<em>Bmal1</em>-ELuc) reporter were exposed to imeglimin (0.1 or 1 mM), metformin (0.1 or 1 mM), a nicotinamide phosphoribosyltransferase inhibitor FK866, and/or vehicle. Subsequently, <em>Bmal1</em>-ELuc expression and clock gene mRNA expression levels were measured at 10-min intervals for 55 h and 4-h intervals for 32 h, respectively.</p></div><div><h3>Results</h3><p>Imeglimin significantly prolonged the period (from 26.3 to 30.0 h at 0.1 mM) and dose-dependently increased the amplitude (9.6-fold at 1 mM) of the <em>Bmal1</em>-ELuc expression rhythm; however, metformin exhibited minimal effects on these parameters. Moreover, imeglimin notably impacted the rhythmic mRNA expression of clock genes (<em>Bmal1</em>, <em>Per1,</em> and <em>Cry1</em>). The concurrent addition of FK866 partly inhibited the effects of imeglimin on both <em>Bmal1</em>-ELuc expression and clock gene mRNA expression.</p></div><div><h3>Conclusion</h3><p>Collectively, these results reveal that imeglimin profoundly affects the circadian clock in MEFs. Further studies are needed to evaluate whether imeglimin treatment could exert similar effects <em>in vivo</em>.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 4","pages":"Pages 215-220"},"PeriodicalIF":3.5,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49866573","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

Therapeutic effect of allicin in a mouse model of intracerebral hemorrhage 大蒜素对脑出血小鼠模型的治疗作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-10-02 DOI: 10.1016/j.jphs.2023.09.007

Yara Atef , Keita Kinoshita , Yusei Ichihara , Keisuke Ushida , Yuma Hirata , Yuki Kurauchi , Takahiro Seki , Hiroshi Katsuki

{"title":"Therapeutic effect of allicin in a mouse model of intracerebral hemorrhage","authors":"Yara Atef , Keita Kinoshita , Yusei Ichihara , Keisuke Ushida , Yuma Hirata , Yuki Kurauchi , Takahiro Seki , Hiroshi Katsuki","doi":"10.1016/j.jphs.2023.09.007","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.09.007","url":null,"abstract":"<div><p>Natural compounds with sulfur moiety produce various biological actions that may be beneficial for the therapies of several devastative disorders of the central nervous system. Here we investigated potential therapeutic effect of allicin, an organosulfur compound derived from garlic, in a mouse model of intracerebral hemorrhage (ICH) based on intrastriatal collagenase injection. Daily intraperitoneal administration of allicin (50 mg/kg) from 3 h after induction of ICH afforded neuroprotective effects, as evidenced by the increase of surviving neurons in the hematoma, reduction of axonal transport impairment, and prevention of axon tract injury. In addition, allicin inhibited accumulation of activated microglia/macrophages around the hematoma and infiltration of neutrophils within the hematoma. Allicin also suppressed ICH-induced mRNA upregulation of pro-inflammatory factors such as interleukin 6 and C-X-C motif ligand 2 in the brain, suggesting its anti-inflammatory effect. Moreover, ICH-induced increase of malondialdehyde as well as decrease of total glutathione in the brain was attenuated by allicin. Finally, allicin-treated mice showed better recovery of sensorimotor functions after ICH than vehicle-treated mice. These results indicate that allicin produces a therapeutic effect on ICH pathology via alleviation of neuronal damage, inflammatory responses and oxidative stress in the brain.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 4","pages":"Pages 208-214"},"PeriodicalIF":3.5,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49866568","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

Therapeutic targets in the brain for overactive bladder: A focus on angiotensin II type 1 receptor 膀胱过度活动症的大脑治疗靶点：血管紧张素II 1型受体的研究

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-10-01 DOI: 10.1016/j.jphs.2023.07.005

Shogo Shimizu

{"title":"Therapeutic targets in the brain for overactive bladder: A focus on angiotensin II type 1 receptor","authors":"Shogo Shimizu","doi":"10.1016/j.jphs.2023.07.005","DOIUrl":"10.1016/j.jphs.2023.07.005","url":null,"abstract":"<div><p>Overactive bladder is a condition that affects both men and women, and significantly affects patients' quality of life. Anticholinergics, β<sub>3</sub>-adrenoceptor agonists, and botulinum toxin are currently being used for treatment. However, several patients do not respond to these medications or discontinue them because of adverse events.</p><p>Angiotensin II (Ang II) is a neuropeptide produced in both brain and peripheral tissues, and Ang II type 1 (AT1) receptors, which are important regions for the micturition reflex, are widely expressed in the cerebral cortex, paraventricular nucleus, solitary tract nucleus, and periaqueductal gray. Our data showed that cumulative central Ang II administration, even at low doses, shortened the intercontraction interval without affecting the blood pressure or blood catecholamine levels. Additionally, Ang II can enhance the micturition reflex by suppressing the GABAergic nervous system and stimulating the downstream pathway of the AT1 receptor. The peripherally administered AT1 receptor blocker telmisartan inhibited central Ang II-induced facilitation of the micturition reflex. Targeting the central AT1 receptor may be a potential treatment approach for patients with overactive bladder. This review introduces the brain AT1 receptor as a therapeutic target in overactive bladder.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 2","pages":"Pages 69-72"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493000","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

Pimaric acid reduces vasoconstriction via BKCa channel activation and VDCC inhibition in rat pulmonary arterial smooth muscles Pimaric acid通过激活BKCa通道和抑制VDCC降低大鼠肺动脉平滑肌的血管收缩

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-10-01 DOI: 10.1016/j.jphs.2023.08.001

Masashi Ishida , Aya Yamamura , Moe Fujiwara , Taiki Amano , Mina Ota , Yukari Hikawa , Rubii Kondo , Yoshiaki Suzuki , Yuji Imaizumi , Hisao Yamamura

引用次数: 0

Schwann cell derived-peroxiredoxin protects motor neurons against hydrogen peroxide-induced cell death in mouse motor neuron cell line NSC-34 雪旺细胞衍生的过氧多辛保护小鼠运动神经元细胞系NSC-34中的运动神经元免受过氧化氢诱导的细胞死亡

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-10-01 DOI: 10.1016/j.jphs.2023.07.006

Akiko Yamamuro-Tanabe , Yasuhiro Kosuge , Yuki Ishimaru , Yasuhiro Yoshioka

{"title":"Schwann cell derived-peroxiredoxin protects motor neurons against hydrogen peroxide-induced cell death in mouse motor neuron cell line NSC-34","authors":"Akiko Yamamuro-Tanabe , Yasuhiro Kosuge , Yuki Ishimaru , Yasuhiro Yoshioka","doi":"10.1016/j.jphs.2023.07.006","DOIUrl":"10.1016/j.jphs.2023.07.006","url":null,"abstract":"<div><p>Schwann cells and oligodendrocytes secrete proteins that promote neuron survival, but their role in amyotrophic lateral sclerosis (ALS) is unclear. To address this question, we evaluated the effect of molecules secreted by Schwann cells on reactive oxygen species (ROS)-induced motor neuronal cell death. We observed that in motor neuron cell line NSC-34 cultures, the conditioned medium (CM) from Schwann cell line YST-1 (YST-1 CM) cultures had a protective effect against hydrogen peroxide-induced cell death. However, this protective effect of YST-1 CM was abolished by removing peroxiredoxin 1–4 (PRDX1–4) from the CM. We found that the expression of PRDX1 mRNA was markedly downregulated in the lumbar spinal cord of the superoxide dismutase 1 (SOD1)<sup>G93A</sup> mouse model of ALS. We also found that transient transfection of YST-1 cells with G93A SOD1 resulted in reduced PRDX1 mRNA expression. Additionally, in the mutant transfected cells, YST-1 CM showed decreased neuroprotective effect against hydrogen peroxide-induced NSC-34 cell death compared to those transfected with WT SOD1. Our results suggest that Schwann cells protect motor neurons from oxidative stress by secreting PRDX1 and that the reduction of PRDX secreted from Schwann cells contributes to increased ROS and associated motor neuronal death in ALS.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 2","pages":"Pages 73-83"},"PeriodicalIF":3.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493001","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

Lactate dehydrogenase A inhibition prevents RANKL-induced osteoclastogenesis by reducing enhanced glycolysis 乳酸脱氢酶A抑制通过减少增强的糖酵解来阻止rankl诱导的破骨细胞生成

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-09-27 DOI: 10.1016/j.jphs.2023.09.005

Tsuyoshi Nishioku, Rumi Anzai, Sami Hiramatsu, Ayaka Terazono, Mamiko Nakao, Miyu Moriyama

{"title":"Lactate dehydrogenase A inhibition prevents RANKL-induced osteoclastogenesis by reducing enhanced glycolysis","authors":"Tsuyoshi Nishioku, Rumi Anzai, Sami Hiramatsu, Ayaka Terazono, Mamiko Nakao, Miyu Moriyama","doi":"10.1016/j.jphs.2023.09.005","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.09.005","url":null,"abstract":"<div><p>Osteoclasts are multinucleated, specializes bone-resorbing cells that are derived from the monocyte/macrophage lineage. Excessive resorbing activities of osteoclasts are involved in destructive bone diseases. The detailed mechanism of acidification at the bone adhesion surface during the bone resorption process of osteoclasts remains to be defined. During glycolysis, pyruvate proceeds to the tricarboxylic cycle under aerobic conditions and pyruvate is converted to lactate via lactate dehydrogenase A (LDHA) under anaerobic conditions. However, tumor cells produce ATP during aerobic glycolysis and large amounts of pyruvate are converted to lactate and H<sup>+</sup> by LDHA. Lactate and H<sup>+</sup> are excreted outside the cell, whereby they are involved in invasion of tumor cells due to the pH drop around the cell. In this study, we focused on aerobic glycolysis and investigated the production of lactate by LDHA in osteoclasts. Expression of LDHA and monocarboxylate transporter 4 (MCT4) was upregulated during osteoclast differentiation. Intracellular and extracellular lactate levels increased with upregulation of LDHA and MCT4, respectively. FX11 (an LDHA inhibitor) inhibited osteoclast differentiation and suppressed the bone-resorbing activity of osteoclasts. We propose that inhibition of LDHA may represent a novel therapeutic strategy for controlling excessive bone resorption in osteoporosis and rheumatoid arthritis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 4","pages":"Pages 197-207"},"PeriodicalIF":3.5,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49866569","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

Regulatory action of PGRMC1 on cyclic AMP-mediated COX2 expression in human endometrial cells PGRMC1对环amp介导的人子宫内膜细胞COX2表达的调控作用

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-09-27 DOI: 10.1016/j.jphs.2023.09.006

Atsuya Tsuru , Mikihiro Yoshie , Ryota Negishi , Toko Mukoyama , Ryo Yonekawa , Junya Kojima , Mana Azumi , Kazuya Kusama , Hirotaka Nishi , Kazuhiro Tamura

{"title":"Regulatory action of PGRMC1 on cyclic AMP-mediated COX2 expression in human endometrial cells","authors":"Atsuya Tsuru , Mikihiro Yoshie , Ryota Negishi , Toko Mukoyama , Ryo Yonekawa , Junya Kojima , Mana Azumi , Kazuya Kusama , Hirotaka Nishi , Kazuhiro Tamura","doi":"10.1016/j.jphs.2023.09.006","DOIUrl":"https://doi.org/10.1016/j.jphs.2023.09.006","url":null,"abstract":"<div><p>Human endometrial stromal cells (ESCs) undergo differentiation, known as decidualization, and endometrial epithelial cells mature around the embryo implantation stage. In the uterus, cyclooxygenase 2 (COX2), the rate-limiting enzyme that produces prostaglandin E2, is expressed in endometrial stromal and epithelial cells, and promotes decidualization of the former cells. Our recent study demonstrated that progesterone receptor membrane component 1 (PGRMC1) is downregulated during decidualization and may be involved in cellular senescence associated with decidualization via the transcription factor forkhead box protein O1 (FOXO1). Therefore, we investigated the role of PGRMC1 in COX2 expression during differentiation and maturation of endometrial stromal and epithelial cells. Inhibition or knockdown of PGRMC1 significantly enhanced differentiation stimuli-induced COX2 expression in both cell types. However, this COX2 expression was suppressed by FOXO1 knockdown or nuclear factor-kappa B (NF-κB) inhibition. Silencing of COX2 expression inhibited PGRMC1 knockdown-induced expression of decidual markers in ESCs. Thus, PGRMC1 may be linked to FOXO1- and NF-κB-mediated COX2 expression in endometrial cells. Taken together, our data suggest that downregulation of PGRMC1 expression facilitates differentiation of endometrial cells, i.e., decidualization and glandular maturation, via upregulation of COX2 expression.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 4","pages":"Pages 188-196"},"PeriodicalIF":3.5,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49866570","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

Characterization of spinal microglial activation in a mouse model of imiquimod-induced psoriasis 吡喹莫德诱导的牛皮癣小鼠模型中脊髓小胶质细胞活化的表征

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-09-20 DOI: 10.1016/j.jphs.2023.09.004

Fumihiro Saika , Yohji Fukazawa , Shiroh Kishioka , Norikazu Kiguchi

引用次数: 0

The influence of OATP2B1 and atorvastatin on coproporphyrin isomers in rats OATP2B1和阿托伐他汀对大鼠比例卟啉异构体的影响

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-09-14 DOI: 10.1016/j.jphs.2023.09.003

Jonny Kinzi , Markus Grube , Janine Hussner , Isabell Seibert , Matthias Hamburger , Henriette E. Meyer zu Schwabedissen

引用次数: 0

Usefulness and difficulties with the thiopurine pharmacogenomic NUDT15 genotyping test: Analysis of real-world data in Japan 硫嘌呤药物基因组学NUDT15基因分型试验的有用性和困难:日本真实世界数据的分析

IF 3.5 3区医学

Journal of pharmacological sciences Pub Date : 2023-09-11 DOI: 10.1016/j.jphs.2023.09.002

Yoichi Kakuta , Motohiro Kato , Yusuke Shimoyama , Takeo Naito , Rintaro Moroi , Masatake Kuroha , Hisashi Shiga , Yoshitaka Kinouchi , Atsushi Masamune

{"title":"Usefulness and difficulties with the thiopurine pharmacogenomic NUDT15 genotyping test: Analysis of real-world data in Japan","authors":"Yoichi Kakuta , Motohiro Kato , Yusuke Shimoyama , Takeo Naito , Rintaro Moroi , Masatake Kuroha , Hisashi Shiga , Yoshitaka Kinouchi , Atsushi Masamune","doi":"10.1016/j.jphs.2023.09.002","DOIUrl":"10.1016/j.jphs.2023.09.002","url":null,"abstract":"<div><p>The usefulness of <em>NUDT15</em> genotyping as a pharmacogenomic test for thiopurine has been established. The first such test developed to date, <em>NUDT15</em> genotyping was approved for reimbursement in Japan in February 2019 for all indicated patients. We retrospectively examined claims data in Japan and confirmed that the proportion of patients who undergo genotyping before initiating a new thiopurine regimen has increased; furthermore, genotyping has improved the rate of treatment continuation and reduced on-treatment hospitalization. However, the genotyping rate before thiopurine induction was >50% for patients with inflammatory bowel disease and <20% for those with other immune-related diseases, indicating significant variation by disease field. Additionally, over 10% of tests were found to have been performed inappropriately, such as multiple genotyping of the same patient or testing more than 2 weeks after starting treatment. Although <em>NUDT15</em> genotyping for patients requiring thiopurine treatment has been shown to improve thiopurine treatment continuation rate, measures are required to address the systematic issues identified in our analysis.</p></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"153 3","pages":"Pages 161-169"},"PeriodicalIF":3.5,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41136019","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