Journal of pharmacological sciences最新文献

HIF-1α stabilization in osteoclasts induces the expression of aerobic glycolysis-related proteins GLUT1, LDHA, and MCT4 破骨细胞中HIF-1α的稳定诱导了有氧糖酵解相关蛋白GLUT1、LDHA和MCT4的表达

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-26 DOI: 10.1016/j.jphs.2025.05.017

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

{"title":"HIF-1α stabilization in osteoclasts induces the expression of aerobic glycolysis-related proteins GLUT1, LDHA, and MCT4","authors":"Tsuyoshi Nishioku, Sae Nakao, Rumi Anzai, Sami Hiramatsu, Akiko Momono, Miyu Moriyama, Mamiko Nakao, Ayaka Terazono","doi":"10.1016/j.jphs.2025.05.017","DOIUrl":"10.1016/j.jphs.2025.05.017","url":null,"abstract":"<div><div>Hypoxia-inducible factor (HIF)-1α is a master transcription factor regulating hypoxic adaptation and activates the transcription of genes involved in various steps of energy metabolism. However, some subsets of cancer cells exhibit high HIF-1α levels regardless of the oxygen concentration. Even under normoxic and normoglycemic conditions, HIF-1α regulates basal expression of its target genes. Osteoclasts are giant multinucleated cells derived from the monocyte/macrophage lineage and are specialized in bone resorption. Excessive osteoclast resorbing activities is involved in destructive bone diseases. There are few data regarding how HIF-1α affects osteoclast differentiation. In this study, we investigated whether echinomycin, a HIF-1α inhibitor, reduced the expression of proteins of aerobic glycolysis, such as glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 4 (MCT4), and whether HIF-1α stabilization is involved in osteoclast differentiation. HIF-1α was stabilized earlier than the upregulation of GLUT1, LDHA, and MCT4 expression during osteoclast differentiation. Echinomycin inhibited GLUT1, LDHA, and MCT4 expression. It also inhibited osteoclast differentiation and suppressed osteoclast bone-resorbing activity. We propose that HIF-1α inhibition suppresses excessive osteoclast differentiation and may represent a novel therapeutic strategy for controlling excessive bone resorption in osteoporosis and rheumatoid arthritis.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 336-342"},"PeriodicalIF":3.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144178600","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

Inhibitory effects of schisandrin A on contractions induced by spasmogenic candidates in porcine coronary arteries 五味子素A对猪冠状动脉痉挛候选物引起的收缩的抑制作用

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-24 DOI: 10.1016/j.jphs.2025.05.016

Qianghaodi Hong, Naho Takazakura, Hideaki Ozawa, Sakika Ichihara, Kento Yoshioka, Keisuke Obara, Yoshio Tanaka

{"title":"Inhibitory effects of schisandrin A on contractions induced by spasmogenic candidates in porcine coronary arteries","authors":"Qianghaodi Hong, Naho Takazakura, Hideaki Ozawa, Sakika Ichihara, Kento Yoshioka, Keisuke Obara, Yoshio Tanaka","doi":"10.1016/j.jphs.2025.05.016","DOIUrl":"10.1016/j.jphs.2025.05.016","url":null,"abstract":"<div><div>The inhibitory effects and underlying mechanisms of schisandrin A (SA) on contractions induced by spasmogenic candidates and related chemicals were investigated in porcine coronary arteries (PCAs). SA (10<sup>−5</sup>–10<sup>−4</sup> M) inhibited contractions induced by acetylcholine, histamine, serotonin, U46619 (thromboxane A<sub>2</sub> mimetic), prostaglandin F<sub>2α</sub>, and endothelin-1 in a concentration-dependent manner. The inhibition of acetylcholine-induced contractions by SA was stronger than that by diltiazem, although both SA and diltiazem ultimately achieved similar levels of inhibition against other contractions. SA also inhibited high-KCl-induced contractions in PCAs and suppressed high-KCl-induced increases in intracellular Ca<sup>2+</sup> concentrations in A7r5 cells. However, SA (10<sup>−4</sup> M) did not inhibit SKF-96365-sensitive phenylephrine-induced contractions, despite potently inhibiting high-KCl-induced contraction in the guinea pig thoracic aorta. SA did not strongly inhibit NaF-induced contractions in Ca<sup>2+</sup>-free solution containing 0.2 mM EGTA. Furthermore, SA inhibited muscarinic receptor binding in mouse cerebral cortex and inhibited carbachol-induced increases in intracellular Ca<sup>2+</sup> concentrations in 293T cells expressing muscarinic M<sub>3</sub> receptors. These findings indicate that SA inhibits coronary artery contractions induced by spasmogens primarily through the inhibition of L-type Ca<sup>2+</sup> channels (LCCs) and exerts an anticholinergic and LCC inhibitory effect on acetylcholine-induced contractions.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 343-352"},"PeriodicalIF":3.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184402","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

Targeting CD38 to alleviate brain endothelial cell dysfunction and cognitive impairment in vascular dementia 靶向CD38缓解血管性痴呆患者脑内皮细胞功能障碍和认知障碍

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-21 DOI: 10.1016/j.jphs.2025.05.013

Mingjing Yu , Zhi Qi , Jiaxin Zhang , Ziyi Zhang , Jieli Chen , Tao Yan , Zhili Chen

{"title":"Targeting CD38 to alleviate brain endothelial cell dysfunction and cognitive impairment in vascular dementia","authors":"Mingjing Yu , Zhi Qi , Jiaxin Zhang , Ziyi Zhang , Jieli Chen , Tao Yan , Zhili Chen","doi":"10.1016/j.jphs.2025.05.013","DOIUrl":"10.1016/j.jphs.2025.05.013","url":null,"abstract":"<div><div>Vascular dementia (VaD) is a leading cause of cognitive decline, closely associated with cerebrovascular endothelial cell (CEC) dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation. CD38, an enzyme implicated in neuroinflammation and cellular senescence, has emerged as a potential regulator of these pathological processes, yet its role in CEC dysfunction within the context of VaD remains unclear. In this study, we investigated the impact of CD38 on CEC dysfunction using a mouse model of VaD induced by bilateral common carotid artery stenosis (BCAS). Our results demonstrate that BCAS significantly reduces cerebral blood flow (CBF), increases BBB permeability, and induces cognitive deficits, all accompanied by elevated CD38 expression in CECs and heightened levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Notably, treatment with the selective CD38 inhibitor 78c (10 mg/kg, twice daily for 1 month) effectively mitigated these effects, reducing white matter damage, improving CBF, enhancing the expression of CEC tight junction proteins, and decreasing neuroinflammation and BBB disruption. In vitro experiments further revealed that 78c attenuates TNF-α-induced CD38 expression and inflammatory responses in CECs, likely through the NOX4/eNOS aixs. These findings identify CD38 as a crucial mediator of CEC dysfunction in VaD, linking chronic cerebral hypoperfusion to neurovascular damage.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 310-321"},"PeriodicalIF":3.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124443","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

Inhibition of CYP1B1 by miR-200b-3p increases the sensitivity of paclitaxel in hepatocellular carcinoma treatment miR-200b-3p抑制CYP1B1可增加紫杉醇治疗肝癌的敏感性

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-21 DOI: 10.1016/j.jphs.2025.05.014

Jiaqi Wang , Jiayi Wu , Haihong Hu , Lushan Yu , Xiaoli Zheng , Su Zeng

引用次数: 0

Tomatidine attenuates post-stroke cognitive impairment by reducing neuroinflammation through prevention of M1 microglial polarization via NF-κB signaling 番茄碱通过NF-κB信号传导预防M1小胶质细胞极化，减轻神经炎症，从而减轻脑卒中后认知障碍

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-15 DOI: 10.1016/j.jphs.2025.05.011

Ayami Kita, Yuka Kawade, Haruyoshi Murakami, Rei Ikeda, Ryota Araki, Takeshi Yabe

{"title":"Tomatidine attenuates post-stroke cognitive impairment by reducing neuroinflammation through prevention of M1 microglial polarization via NF-κB signaling","authors":"Ayami Kita, Yuka Kawade, Haruyoshi Murakami, Rei Ikeda, Ryota Araki, Takeshi Yabe","doi":"10.1016/j.jphs.2025.05.011","DOIUrl":"10.1016/j.jphs.2025.05.011","url":null,"abstract":"<div><div>Post-stroke cognitive impairment (PSCI) is a clinical disorder that commonly occurs after a stroke and may persist long-term in most stroke survivors. Neuroinflammation involving proinflammatory M1 microglia, an activated microglial phenotype after stroke injury, is a major risk factor for PSCI. Tomatidine is a steroidal alkaloid of immature green tomatoes that has anti-inflammatory properties. To investigate the effects of tomatidine on cognitive impairment and microglial-associated neuroinflammation after stroke, we performed behavioral experiments and analyses on activated microglia in a transient bilateral common carotid arteries occlusion (tBCCAO) mouse model. Tomatidine attenuated cognitive impairment and neurodegeneration in the CA1 and CA3 hippocampal regions and reduced microglial activation and polarization into an M1 phenotype in the hippocampus in tBCCAO mice. The direct effect of tomatidine on polarization into the M1 phenotype was examined using LPS-stimulated BV2 microglia, as an M1 microglia model. Tomatidine reduced expression of M1 microglial markers and inflammatory mediators and inhibited nuclear translocation and phosphorylation of NF-κB in LPS-treated BV2 microglia. These results suggest that tomatidine suppresses microglial polarization into an M1 phenotype via modulation of NF-κB signaling, resulting in attenuation of neuroinflammation and reduction of PSCI.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 294-302"},"PeriodicalIF":3.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105737","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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Ferulic acid suppresses guinea pig ileal longitudinal smooth muscle contractions by inhibiting voltage-dependent Ca2+ channels 阿魏酸通过抑制电压依赖性Ca2+通道抑制豚鼠回肠纵向平滑肌收缩

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-14 DOI: 10.1016/j.jphs.2025.05.012

Keisuke Obara , Kento Yoshioka , Aya Shimada, Sakika Ichihara, Wakaba Kinami, Futaba Makino, Naho Takazakura, Miwa Enomoto, Yoshio Tanaka

引用次数: 0

Exposure of Zinc-induced Parkinson's disease-like non-motor and motor symptoms in relation to oxidative/nitrosative stress mediated neurodegeneration in the brain of Drosophila melanogaster 暴露于锌诱导的帕金森病样非运动和运动症状与氧化/亚硝化应激介导的黑腹果蝇大脑神经变性有关

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-14 DOI: 10.1016/j.jphs.2025.05.010

Abhishek P.R. Nadiga , K.L. Krishna , Afrasim Moin , Amr Selim Abu Lila , Syed Mohd Danish Rizvi , Sahyadri M. , Suman Pathak , Shahanawaz Syed , El-Sayed Khafagy

{"title":"Exposure of Zinc-induced Parkinson's disease-like non-motor and motor symptoms in relation to oxidative/nitrosative stress mediated neurodegeneration in the brain of Drosophila melanogaster","authors":"Abhishek P.R. Nadiga , K.L. Krishna , Afrasim Moin , Amr Selim Abu Lila , Syed Mohd Danish Rizvi , Sahyadri M. , Suman Pathak , Shahanawaz Syed , El-Sayed Khafagy","doi":"10.1016/j.jphs.2025.05.010","DOIUrl":"10.1016/j.jphs.2025.05.010","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the second most prevalent idiopathic neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to locomotor impairment. Despite extensive research, the etiology of PD remains unclear, and existing experimental models for pharmacological evaluation do not fully replicate the disease's hallmarks, necessitating the development of a cost-effective and reliable alternative. In recent past, Drosophila melanogaster has been utilized as a model organism for various neurodegenerative diseases, including PD. The present study was conceptualized to develop a reliable PD model in the Drosophila by Zinc (Zn<sup>+2</sup>).Chronic exposure to 20 mM Zn<sup>+2</sup> for 7 days exhibited non-motor and motor PD-like symptoms in adult Drosophila flies, with reduced locomotory activity, indicating motor function deficit and reduced olfactory function and courtship behavior, indicating a deficit in non-motor function. These behavioral symptoms were associated with decreased dopamine levels. Furthermore, chronic Zn<sup>+2</sup> exposure resulted in enhanced membrane lipid peroxidation and decreased endogenous antioxidants level in the Drosophila brain. These effects were primarily mediated by oxidative/nitrosative stress pathway. Thus, Zn<sup>2+</sup>-induced PD in Drosophila serves as a cost-effective model for drug discovery, facilitating the screening of potential therapeutic compounds. Additionally, this model offers a valuable platform to investigate the molecular mechanisms underlying PD pathophysiology.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Pages 303-309"},"PeriodicalIF":3.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124444","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

Inhibitory effects of γ-linolenic acid on contractile responses in pig coronary arteries: Possible involvement of prostanoid TP receptor inhibition γ-亚麻酸对猪冠状动脉收缩反应的抑制作用：可能与前列腺素TP受体抑制有关

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-12 DOI: 10.1016/j.jphs.2025.05.009

Keisuke Obara , Kento Yoshioka , Mikoto Ozawa, Haruki Kimura, Mayu Kiguchi, Yuri Nakao, Hinako Miyaji, Toma Yamashita, Noboru Saitoh, Yutaka Nakagome, Sakika Ichihara, Yoshio Tanaka

引用次数: 0

Improved serotonin neuron-specific viral vectors applicable for optogenetic manipulation and recording 改良的5 -羟色胺神经元特异性病毒载体，适用于光遗传操作和记录

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-08 DOI: 10.1016/j.jphs.2025.05.008

Takuma Noguchi , Harune Hori , Koji Toda , Hisashi Shirakawa , Hitoshi Hashimoto , Kazuki Nagayasu

引用次数: 0

Centrally administered prostaglandin E2 suppresses the micturition reflex in rats 中央给药前列腺素E2抑制大鼠排尿反射

IF 3 3区医学

Journal of pharmacological sciences Pub Date : 2025-05-07 DOI: 10.1016/j.jphs.2025.05.005

Takahiro Shimizu , Nobutaka Shimizu , Shun Tsubouchi , Mio Togo , Youichirou Higashi , Motoaki Saito

{"title":"Centrally administered prostaglandin E2 suppresses the micturition reflex in rats","authors":"Takahiro Shimizu , Nobutaka Shimizu , Shun Tsubouchi , Mio Togo , Youichirou Higashi , Motoaki Saito","doi":"10.1016/j.jphs.2025.05.005","DOIUrl":"10.1016/j.jphs.2025.05.005","url":null,"abstract":"<div><div>Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) facilitates the micturition reflex at the lower urinary tract and spinal cord levels. However, the roles of brain PGE<sub>2</sub> in reflex regulation remain unclear. Therefore, we aimed to investigate the effects of intracerebroventricularly administered PGE<sub>2</sub> on the micturition reflex. We further investigated whether the PGE<sub>2</sub>-induced responses were dependent on the sympathetic nervous system (SNS) and identified the brain E-prostanoid receptor subtypes (EP<sub>1</sub>–EP<sub>4</sub>) involved in PGE<sub>2</sub>-induced effects. Intracerebroventricularly administered PGE<sub>2</sub> (0.1, 0.3, or 1 nmol/rat) dose-dependently increased the intercontraction intervals (ICI) and threshold pressure required to induce micturition (TP) without altering maximal voiding pressure in urethane-anesthetized (0.8 g/kg, ip) male rats. PGE<sub>2</sub> (1 nmol/rat) significantly increased the mean blood pressure; 6-hydroxydopamine-induced chemical sympathectomy ameliorated this increase. In contrast, chemical sympathectomy had no significant effect on the PGE<sub>2</sub>-induced increases in ICI and TP. Intracerebroventricularly pretreated SC51322 (EP<sub>1</sub> receptor antagonist, 100 nmol/rat) and PF04418948 (EP<sub>2</sub> receptor antagonist, 100 nmol/rat), but not L-798106 (EP<sub>3</sub> receptor antagonist, 100 nmol/rat) or L-161982 (EP<sub>4</sub> receptor antagonist, 100 nmol/rat), significantly attenuated the PGE<sub>2</sub> (1 nmol/rat)-induced changes in ICI and TP. These results suggest that centrally administered PGE<sub>2</sub> suppresses the rat micturition reflex through brain EP<sub>1</sub> and EP<sub>2</sub> receptors, independent of SNS activation.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 231-237"},"PeriodicalIF":3.0,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931633","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