Journal of pharmacological sciences最新文献

{"title":"Wireless recording and autoencoder denoising of intestinal activity in freely moving rats","authors":"Yamato Ishii ,&nbsp;Nobuyoshi Matsumoto ,&nbsp;Yuji Ikegaya ,&nbsp;Tetsuhiko Kashima","doi":"10.1016/j.jphs.2025.03.005","DOIUrl":"10.1016/j.jphs.2025.03.005","url":null,"abstract":"<div><div>Conventional wired systems for recording intestinal motility using strain-gauge transducers physically limit animal movement and are not ideal for long-term studies. Here, we developed a wireless recording system that allows continuous monitoring of intestinal activity in freely moving rats. We also developed a denoising autoencoder that isolates intestinal motility signals from locomotor noise while maintaining a 10-s temporal resolution. The refined data revealed decreased intestinal motility while the rats were behaviorally active. This system has broad applications for in vivo physiological research.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 54-58"},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mirogabalin and pregabalin alleviate nociplastic sensitization induced by chemogenetic activation of the central amygdala neurons in rodents","authors":"Manami Yajima ,&nbsp;Yukari Takahashi ,&nbsp;Yasuhito Uezono ,&nbsp;Fusao Kato","doi":"10.1016/j.jphs.2025.03.004","DOIUrl":"10.1016/j.jphs.2025.03.004","url":null,"abstract":"<div><div>Nociplastic pain represents the third mechanistic descriptor of pain, alongside neuropathic and nociceptive pain, as proposed in 2017 by the International Association for the Study of Pain (IASP). It describes pain occurring in the absence of nociceptor activation, tissue damage, or neuropathy. The underlying brain mechanisms of nociplastic pain remain poorly understood. Despite the potentially large patient population with chronic pain of this class, effective pharmacological treatments for nociplastic pain are still limited, highlighting the urgent need for drug development using appropriate preclinical models.</div><div>In this study, we investigated the anti-sensitization effects of two gabapentinoids—mirogabalin besylate (MGB) and pregabalin (PGB)—using a rodent model of nociplastic pain. This model involves experimental excitation of central amygdala neurons via designer receptors exclusively activated by designer drugs (DREADDs), causing widespread sensitization. Administration of an artificial ligand, deschloroclozapine (DCZ; 0.1 mg/kg, i.p.), significantly reduced the 50 %-paw withdrawal threshold, which was significantly elevated by MGB (10 mg/kg, i.p.) and PGB (30 mg/kg, i.p.), restoring it to levels not significantly different from the pre-DCZ baseline. We conclude that MGB and PGB alleviate widespread sensitization in this nociplastic pain model, likely through their action on α₂δ-1 subunits within brain circuits that regulate pain sensitivity.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 77-83"},"PeriodicalIF":3.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-angiogenic effects of arctigenin on choroidal neovascularization pathogenesis","authors":"Aimi Shirakawa ,&nbsp;Hiroto Yasuda ,&nbsp;Shinsuke Nakamura ,&nbsp;Yuichi Takajo ,&nbsp;Satoshi Inamasu ,&nbsp;Satoshi Yomoda ,&nbsp;Shimpei Watanabe ,&nbsp;Yoshiki Kuse ,&nbsp;Masamitsu Shimazawa","doi":"10.1016/j.jphs.2025.03.003","DOIUrl":"10.1016/j.jphs.2025.03.003","url":null,"abstract":"<div><div>Neovascular age-related macular degeneration (nAMD) is an ocular disease characterized by choroidal neovascularization (CNV), resulting in severe visual impairment. Arctigenin is a natural lignan compound from <em>Arctium lappa</em> L. and has anti-inflammatory and vascular normalizing effects. Here, we investigated the anti-angiogenic effects of arctigenin on CNV formation. Laser-induced CNV model mice were orally administered arctigenin at 100 mg/kg once a day for 5 days before laser irradiation. Oral administration of arctigenin suppressed CNV formation, vascular leakage, and the proliferation of endothelial cells in the CNV lesions. Treatment with arctigenin at 30 μM attenuated vascular endothelial growth factor (VEGF)-induced cell proliferation of human retinal microvascular endothelial cells (HRMECs). Moreover, arctigenin suppressed the phosphorylation of Src, which is involved in VEGF signaling. Arctigenin also inhibited VEGF-induced mitochondrial respiratory activation. These findings suggested that daily intake of arctigenin may have beneficial effects on nAMD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 42-51"},"PeriodicalIF":3.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Puerarin improves MASLD by remodeling intestinal microenvironment to promote mitochondrial fusion and autophagy","authors":"Chunbin Sun ,&nbsp;Mei Du ,&nbsp;Shuang Sha ,&nbsp;Si Wang ,&nbsp;Lei Li ,&nbsp;Jiong Hou ,&nbsp;Li Li ,&nbsp;Jiali Yuan ,&nbsp;Jinyuan Yan ,&nbsp;Zhongshan Yang","doi":"10.1016/j.jphs.2025.03.001","DOIUrl":"10.1016/j.jphs.2025.03.001","url":null,"abstract":"<div><div>Pueraria Mirifica (Willd. Ohwi) is a medicine with anti-inflammatory and lipid-lowering properties. Puerarin is one of the main active components of Pueraria. The aim of this study was to investigate the possible mechanisms of Pueraria in the treatment of non-alcoholic fatty liver disease. The therapeutic effect of the drug was demonstrated by serum and liver pathology indicators. The mechanism of action of puerarin was demonstrated by intestinal microbial changes and short-chain fatty acid content tests. The mechanism of puerarin alleviating Metabolic dysfunction-associated steatotic liver disease (MASLD) by regulating intestinal flora was predicted by bioinformatics. The relationship between flora and liver was revealed by q-PCR detection of mRNA expression level of liver metabolic genes. And the mechanism of puerarin action was further verified by intestinal microbial clearance experiments. Puerarin reduced vacuolar-like changes, lipid deposition, and inflammatory cell infiltration in the livers of high-fat diet (HFD) model mice. The gut microbiota abundance and diversity were remodeled, short-chain fatty acid content was increased, and the intestinal mucosal barrier was repaired, accompanied by a reduction in inflammatory cytokines. Puerarin regulated mRNA expression of hepatic lipid metabolism genes to alleviate MASLD. These results suggested that puerarin treats MASLD by treating altering bacterial metabolism and anti-inflammation.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 27-41"},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Polyphyllin I inhibits growth and invasion of cisplatin-resistant gastric cancer cells by partially inhibiting CIP2A/PP2A/Akt signaling axis” [J Pharmacol Sci 137 (2018) 305–312]","authors":"Yunfei Zhang ,&nbsp;Ping Huang ,&nbsp;Xuewen Liu ,&nbsp;Yuchen Xiang ,&nbsp;Te Zhang ,&nbsp;Yezi Wu ,&nbsp;Jiaxin Xu ,&nbsp;Zhiting Sun ,&nbsp;Weiguo Zhen ,&nbsp;Liang Zhang ,&nbsp;Yuan Si ,&nbsp;Ying Liu","doi":"10.1016/j.jphs.2025.02.009","DOIUrl":"10.1016/j.jphs.2025.02.009","url":null,"abstract":"","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 4","pages":"Page 373"},"PeriodicalIF":3.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586117","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}

{"title":"Specnuezhenide and ecliptasaponin A from Ligustrum lucidum Ait and Ecliptae Herba improved premature ovarian failure by targeting the ESR1","authors":"Jia Xu ,&nbsp;Lei Lei ,&nbsp;Ping Li ,&nbsp;Zi-Chun Huang ,&nbsp;Ying Meng ,&nbsp;Bing He ,&nbsp;Ji-Lin Kuang","doi":"10.1016/j.jphs.2025.02.011","DOIUrl":"10.1016/j.jphs.2025.02.011","url":null,"abstract":"<div><div>This study was designed to investigate the role of <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> on premature ovarian failure (POF) and the underlying mechanisms. In the POF mouse model constructed using cyclophosphamide (CTX), <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> increased ovarian index and estradiol (E2) levels and curtailed motility and follicle-stimulating hormone (FSH). <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> alleviated ovarian pathological damage in POF mice and promoted the expression of ovarian CD31 and Vascular Endothelial Growth Factor A (VEGFA). Through high-performance liquid chromatography-mass spectrometry (HPLC-MS) and network pharmacology, Specnuezhenide and ecliptasaponin A were identified as the key components of <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> in anti-POF action. The important target associated with these components is Estrogen Receptor (ESR) 1. Molecular docking and <em>in vitro</em> experiments showed that Specnuezhenide and ecliptasaponin A can both bind to the ESR protein; knocking down ESR1 inhibited the anti-apoptotic effect of Specnuezhenide and ecliptasaponin A on CTX-induced POF cells. In conclusion, the key components of <em>Ligustrum lucidum Ait</em> and <em>Ecliptae Herba</em> that alleviate POF are Specnuezhenide and ecliptasaponin A, which improve the condition by upregulating ESR1.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 13-26"},"PeriodicalIF":3.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible involvement of α, β-unsaturated carbonyl compounds in ferroptosis induced by the cigarette smoke extract of heated tobacco products in vascular smooth muscle cells","authors":"Takahiro Horinouchi ,&nbsp;Yuichi Mazaki ,&nbsp;Soichi Miwa","doi":"10.1016/j.jphs.2025.02.010","DOIUrl":"10.1016/j.jphs.2025.02.010","url":null,"abstract":"<div><div>In this study, we aimed to determine the cytotoxic factors involved in ferroptosis induced by nicotine- and tar-free cigarette smoke extract (CSE) from heated tobacco products (HTPs) in vascular smooth muscle cells. CSE decreased mitochondrial metabolic activity and increased lactate dehydrogenase leakage. These cytotoxic effects completely disappeared after removing the carbonyls from the mainstream smoke. α, β-Unsaturated carbonyl compounds (acrolein, methyl vinyl ketone, crotonaldehyde, and methacrolein) in the mainstream smoke of HTPs and CSE caused cell damage, which was inhibited by a ferroptosis inhibitor, UAMC-3203. These results suggest that α, β-unsaturated carbonyl compounds might be involved in CSE-induced ferroptosis.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 8-12"},"PeriodicalIF":3.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Senescent cardiac fibroblasts-derived extracellular vesicles induced autophagy in cardiac fibroblasts via suppression of ras homolog enriched in brain like 1","authors":"Yusei Fujioka,&nbsp;Kosuke Otani,&nbsp;Muneyoshi Okada,&nbsp;Hideyuki Yamawaki","doi":"10.1016/j.jphs.2025.02.007","DOIUrl":"10.1016/j.jphs.2025.02.007","url":null,"abstract":"<div><div>Cardiac fibroblasts (CFs) play roles in the maintenance of myocardial tissue structure. Cellular senescence is a state of stable cell cycle arrest. We previously reported that extracellular vesicles (EV) secreted by doxorubicin (DOX, 1000 nM)-induced senescent CFs (D10³-EV) caused autophagy in CFs. EV mediate cell-to-cell communication through the transfer of microRNA (miRNA). In this study, we focused on miRNA contained in EV and aimed to elucidate mechanisms underlying the autophagy induction by D10³-EV in CFs. Neonatal rat CFs (NRCFs) were treated with DOX for the induction of cellular senescence. EV were isolated from culture media of NRCFs. miRNA was extracted from the EV and miRNA profiles were analyzed using miRNA-seq. Seven miRNAs were significantly decreased, whereas 14 miRNAs were significantly increased in D10³-EV compared with the vehicle-treated NRCFs-derived EV. Among the target genes of 14 miRNAs, <em>Rhebl1</em> was identified. D10³-EV significantly increased microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I and decreased protein expression of Ras homolog enriched in brain like 1 (RHEBL1) in NRCFs. Small interfering RNA against <em>Rhebl1</em> tended to increase LC3-II/LC3-I. In conclusion, we for the first time revealed that the senescent NRCFs-derived EV induced autophagy in NRCFs via the suppression of RHEBL1 protein.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 1","pages":"Pages 1-7"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Midnolin gene expression is enhanced by Gq-coupled muscarinic acetylcholine receptor stimulation in SH-SY5Y human neuroblastoma cells","authors":"Ikuo Norota ,&nbsp;Yusuke Zuiki ,&nbsp;Ayano Chiba ,&nbsp;Mikako Nagashima ,&nbsp;Jiro Ogura ,&nbsp;Hiroaki Yamaguchi ,&nbsp;Kuniaki Ishii ,&nbsp;Yutaro Obara","doi":"10.1016/j.jphs.2025.02.006","DOIUrl":"10.1016/j.jphs.2025.02.006","url":null,"abstract":"<div><div>We previously demonstrated that the midnolin gene (<em>MIDN</em>) is a risk factor for Parkinson's disease (PD) in Yamagata and British cohorts, and that neurite outgrowth is abolished by <em>MIDN</em> knockout in PC12 cells. Therefore, drugs that upregulate <em>MIDN</em> may have neurotrophic effects. In this study, acetylcholine increased <em>MIDN</em> promoter activity and gene expression in a concentration-dependent manner in SH-SY5Y cells. These effects were suppressed by atropine and a G_q inhibitor, YM254890, indicating that muscarinic receptor/G_q signaling is required for the induction of <em>MIDN</em> by acetylcholine. Our findings suggest that drugs that upregulate <em>MIDN</em> may have therapeutic potential for PD.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 4","pages":"Pages 229-232"},"PeriodicalIF":3.0,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of netrin-1/DCC signaling pathway by Jiawei Kongsheng Zhenzhong Pill improves synaptic structural plasticity in PSD rats","authors":"Yue Zhao ,&nbsp;Aizhen Song ,&nbsp;Guowei Liu ,&nbsp;Qiuyue Chen ,&nbsp;Qiaolan Wu ,&nbsp;Zu Gao ,&nbsp;Zifa Li ,&nbsp;Huayun Yu ,&nbsp;Zhichun Wu","doi":"10.1016/j.jphs.2025.02.004","DOIUrl":"10.1016/j.jphs.2025.02.004","url":null,"abstract":"<div><div>Jiawei Kongsheng Zhenzhong Pill(JKZP) is based on Kongsheng Zhenzhong Pill contained in the Tang Dynasty's “<em>Thousand Golden Prescriptions</em>,” which exhibited good anti-ischemic and antidepressant effects in the previous study. However, its specific effects on post-stroke depression (PSD) and the mechanism are not clear. This study aimed to investigate the effects of JKZP in the treatment of PSD and related mechanisms. The decoction of JKZP was first analyzed for its medicinal chemical composition and screened for representative components of JKZP. The Middle cerebral artery occlusion (MCAO) method combined with solitary rearing and chronic unpredictable mild stress (CUMS) was used to establish a rat model of PSD, and to observe the effects of JKZP on the behavior and synaptic plasticity of PSD rats, and to investigate the mechanism of JKZP in the treatment of PSD by detecting the mRNA level, protein expression and activity of Netrin-1/DCC signaling pathway-related proteins. The results showed that the JKZP decoction contained loganin, β-asarone and other pharmaceutical ingredients, which have been reported to protect against cerebral ischemic injury and antidepressant effects. JKZP significantly improved the depression-like behavior of PSD rats and improved the damage to pyramidal neurons in the medial prefrontal cortex (mPFC) of PSD rats. Moreover, JKZP increased the density of dendritic spines in the mPFC of PSD rats, improved synaptic gap width and thickness of the post-synaptic density, and increased the number of synaptic vesicles. The results of Real-Time quantitative reverse transcription PCR (qRT-PCR), Western blotting, and pull-down assays revealed that JKZP increased netrin-1, deleted in colorectal cancer (DCC), and focal adhesion kinase (FAK) mRNA and protein expression, elevated the <em>p</em>-FAK/FAK ratio, and decreased myosin II protein expression and Ras homolog gene family member A (RhoA-GTP) activity in the mPFC of PSD rats. Taken together, JKZP can affect synaptic structural remodeling and improve depressive manifestations and neuronal damage in PSD rats by regulating the expression and activity of signaling molecules related to the netrin-1/DCC signaling pathway.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"157 4","pages":"Pages 242-252"},"PeriodicalIF":3.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}