Journal of pharmacological sciences最新文献

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Nerol enhances lipid synthesis in human sebocytes via cannabinoid receptor-2-mediated MAPK signaling 橙花醇通过大麻素受体2介导的MAPK信号传导增强人皮脂细胞的脂质合成
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-29 DOI: 10.1016/j.jphs.2025.04.008
Qi Zhao , Zhiwei Liu , Yong Wang , Tan Li , Juan Wang , Yaozhao Li , Chengliang Li , Chuntao Zhai , Christos C. Zouboulis , Xiaolei Ding , Qiang Ju , Zhenlin Hu
{"title":"Nerol enhances lipid synthesis in human sebocytes via cannabinoid receptor-2-mediated MAPK signaling","authors":"Qi Zhao ,&nbsp;Zhiwei Liu ,&nbsp;Yong Wang ,&nbsp;Tan Li ,&nbsp;Juan Wang ,&nbsp;Yaozhao Li ,&nbsp;Chengliang Li ,&nbsp;Chuntao Zhai ,&nbsp;Christos C. Zouboulis ,&nbsp;Xiaolei Ding ,&nbsp;Qiang Ju ,&nbsp;Zhenlin Hu","doi":"10.1016/j.jphs.2025.04.008","DOIUrl":"10.1016/j.jphs.2025.04.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Nerol, a natural monoterpene, is commonly used as a fragrance additive in perfumes and cosmetics due to its pleasant rose-like aromas. Nerol application possesses diverse pharmacological properties, including anti-microbial, antioxidant, antinociceptive and anti-inflammatory activities, but its effects on sebum production and the consequent skin barrier function remain elusive. Here, we explored the effect of nerol on the lipogenesis of sebocytes.</div></div><div><h3>Patients and methods</h3><div>Immortalized human SZ95 sebocytes were used. The intracellular lipids were quantitatively measured by western blotting or fluorescent Nile Red staining followed by fluorometric analysis, semiquantitative detection or flow cytometry. The cell proliferation and differentiation were detected with CCK8 and flow cytometry, respectively. Moreover, RT-qPCR and immunocytochemistry were used to determine the expression levels of olfactory receptor OR2W3 and cannabinoid receptor-2 (CB2) receptors in SZ95 sebocytes.The mechanism was investigated by RNA interference and Western blotting.</div></div><div><h3>Results</h3><div>Our findings revealed that nerol induced lipid production in SZ95 sebocytes, together with the upregulation of multiple genes related to lipid synthesis, including PPARγ, SREBP-1, and FAS. Nerol also induced sebocyte differentiation, as evidenced by elevated cellular granulation and upregulated differentiation marker genes. Mechanistically, the lipogenic effect of nerol was mediated via CB2, rather than OR2W3 and TRP channels. Moreover, MAPK signaling was involved in neurol's effect.</div></div><div><h3>Conclusion</h3><div>Collectively, our findings show that nerol exerts a lipogenic effect on human sebocytes in a CB2-dependent manner through the activation of MAPK pathway, suggesting the therapeutic potential of this monoterpene in controlling cutaneous disorders involving sebaceous gland dysfunction and reduced sebum production, such as atopic dermatitis, skin dryness and aging.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 219-230"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929574","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
Diurnal variations of neurokinin-1 receptor defines dosing time-dependent differences in antitumor effects of aprepitant in mice 神经激肽-1受体的日变化决定了阿瑞吡坦在小鼠体内抗肿瘤作用的剂量时间依赖性差异
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-25 DOI: 10.1016/j.jphs.2025.04.007
Yoshihiro Seto , Shun Tokeshi , Daisuke Inoue , Fumiyasu Okazaki , Hideto To
{"title":"Diurnal variations of neurokinin-1 receptor defines dosing time-dependent differences in antitumor effects of aprepitant in mice","authors":"Yoshihiro Seto ,&nbsp;Shun Tokeshi ,&nbsp;Daisuke Inoue ,&nbsp;Fumiyasu Okazaki ,&nbsp;Hideto To","doi":"10.1016/j.jphs.2025.04.007","DOIUrl":"10.1016/j.jphs.2025.04.007","url":null,"abstract":"<div><div>Aprepitant, a neurokinin-1 receptor (NK1R) antagonist, has the potential as a novel anticancer agent. This study explored the impact of chronotherapy on the antitumor effect of aprepitant in a mouse model of colorectal carcinoma. Aprepitant inhibited the proliferation of Colon-26 cells <em>in vitro</em> in a concentration-dependent manner and reduced the expression of cell cycle-related genes. Diurnal variations in NK1R mRNA and protein levels were observed in Colon-26 tumors, peaking at zeitgeber time (ZT) 2 and ZT 10, respectively. Administration of aprepitant at ZT 6, achieving peak plasma concentration at ZT 10, significantly reduced the tumor volume compared with administration at ZT 18. Despite the lower plasma concentrations and AUC<sub>0–12 h</sub> in the ZT 6 group, superior antitumor effect suggests a dosing time-dependent efficacy due to variations in NK1R expression rather than its pharmacokinetics. These findings indicate that the antitumor activity of aprepitant against colorectal cancer can be enhanced by aligning its administration with NK1R expression rhythms, warranting further exploration of aprepitant chronotherapy in cancer chemotherapy.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 193-198"},"PeriodicalIF":3.0,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879123","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 ferulic acid on the contraction responses of porcine coronary arteries: a comparison with diltiazem 阿魏酸对猪冠状动脉收缩反应的抑制作用:与地尔硫卓的比较
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-18 DOI: 10.1016/j.jphs.2025.04.006
Kento Yoshioka , Keisuke Obara , Yilin Luo, Qianghaodi Hong, Ayaka Fujiwara, Wakaba Kinami, Hideaki Ozawa, Yoshio Tanaka
{"title":"Inhibitory effects of ferulic acid on the contraction responses of porcine coronary arteries: a comparison with diltiazem","authors":"Kento Yoshioka ,&nbsp;Keisuke Obara ,&nbsp;Yilin Luo,&nbsp;Qianghaodi Hong,&nbsp;Ayaka Fujiwara,&nbsp;Wakaba Kinami,&nbsp;Hideaki Ozawa,&nbsp;Yoshio Tanaka","doi":"10.1016/j.jphs.2025.04.006","DOIUrl":"10.1016/j.jphs.2025.04.006","url":null,"abstract":"<div><div>Ferulic acid (FA) exerts protective effects against cardiovascular-related diseases; however, its role in coronary artery dilation is unclear. Here, we examined the effects and underlying mechanisms of FA in response to contractions induced by spasmogenic candidates in porcine coronary arteries (PCAs). FA (3 × 10<sup>−4</sup>–3 × 10<sup>−3</sup> M) inhibited high-KCl-induced contractions in a concentration-dependent manner, and FA (3 × 10<sup>−4</sup>–10<sup>−3</sup> M) inhibited high-KCl-induced increases in intracellular Ca<sup>2+</sup> concentrations in A7r5 cells. FA (3 × 10<sup>−3</sup> M) showed greater inhibition than diltiazem (3 × 10<sup>−5</sup> M) against chemical-induced contractions but weaker inhibition against high-KCl-induced contractions. FA (3 × 10<sup>−4</sup>–3 × 10<sup>−3</sup> M) inhibited contractions induced by endothelin-1 (10<sup>−8</sup> M) and NaF (10<sup>−2</sup> M) under Ca<sup>2+</sup>-free conditions in a concentration-dependent manner; these contractions were fully suppressed by ML-7 (10<sup>−4</sup> M, a myosin light chain kinase inhibitor). FA (3 × 10<sup>−3</sup> M) also inhibited myosin light chain phosphorylation induced by NaF (10<sup>−2</sup> M) in A7r5 cells regardless of extracellular Ca<sup>2+</sup> conditions. These findings indicate that FA inhibits PCA contractions induced by coronary spasmogens by inhibiting L-type Ca<sup>2+</sup> channels and intracellular routes responsible for extracellular Ca<sup>2+</sup> influx-independent contractions. The latter mechanism may involve the inhibition of myosin light chain phosphorylation-related processes.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 172-181"},"PeriodicalIF":3.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864010","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
Comparative analysis of the single-molecule transport kinetics of OATP1B1 genetic variants OATP1B1基因变异的单分子转运动力学比较分析
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-15 DOI: 10.1016/j.jphs.2025.04.005
Kazunari Tsujii , Kodai Yajima , Takeshi Akiyoshi , Kazuho Sakamoto , Yoshiaki Suzuki , Takayuki Oka , Ayuko Imaoka , Hisao Yamamura , Junko Kurokawa , Hisakazu Ohtani
{"title":"Comparative analysis of the single-molecule transport kinetics of OATP1B1 genetic variants","authors":"Kazunari Tsujii ,&nbsp;Kodai Yajima ,&nbsp;Takeshi Akiyoshi ,&nbsp;Kazuho Sakamoto ,&nbsp;Yoshiaki Suzuki ,&nbsp;Takayuki Oka ,&nbsp;Ayuko Imaoka ,&nbsp;Hisao Yamamura ,&nbsp;Junko Kurokawa ,&nbsp;Hisakazu Ohtani","doi":"10.1016/j.jphs.2025.04.005","DOIUrl":"10.1016/j.jphs.2025.04.005","url":null,"abstract":"<div><div>Several genetic variants of OATP1B1, a hepatic uptake transporter, increase the blood concentrations of substrate drugs, e.g., ∗15 carriers exhibit higher blood substrate concentrations than ∗1b carriers. It remains unclear whether these differences are due to changes in expression or intrinsic activity (transport activity per OATP1B1 molecule). This study compared the intrinsic activity of four OATP1B1 variants, ∗1a, ∗1b, ∗5, and ∗15, using HEK293 cell lines that co-expressed large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (BK) channels and one of the OATP1B1 variants. To estimate the kinetic parameters <em>K</em><sub>m</sub> and <em>V</em><sub>max</sub>, 2′, 7′-dichlorofluorescein uptake was evaluated. The number of OATP molecules per cell (Q<sub>T</sub>) was calculated from BK channel-mediated whole-cell conductance and the OATP1B1/BK channel expression ratio (ρ) (determined by LC-MS/MS). <em>V</em><sub>max,int</sub> (maximum intrinsic transport velocity) was obtained by dividing <em>V</em><sub>max</sub> by Q<sub>T</sub>, and intrinsic clearance (<em>CL</em><sub>int</sub>) was calculated as <em>V</em><sub>max,int</sub>/<em>K</em><sub>m</sub>. The <em>K</em><sub>m</sub> values of ∗1a, ∗1b, ∗5, and ∗15 were 12.5, 9.19, 7.53, and 10.4 μM, and their <em>V</em><sub>max,int</sub> values were 3.0, 7.0, 1.5, and 1.2 × 10<sup>−21</sup> mol/OATP molecule/min, respectively. Accordingly, the <em>CL</em><sub>int</sub> value for OATP1B1∗15 was 15 % lower than that for OATP1B1∗1b, suggesting that the increased blood substrate concentrations observed in OATP1B1∗15 carriers may be due to the decreased intrinsic activity of OATP1B1∗15.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 166-171"},"PeriodicalIF":3.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864009","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
Non-peptidic natural products that target and modulate oxytocin and arginine vasopressin receptors: Opportunities and challenges 靶向和调节催产素和精氨酸抗利尿激素受体的非肽类天然产物:机遇和挑战
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-14 DOI: 10.1016/j.jphs.2025.04.004
Dane Tregeagle , Catherine Doherty , Timothy Callis, Michael Kassiou
{"title":"Non-peptidic natural products that target and modulate oxytocin and arginine vasopressin receptors: Opportunities and challenges","authors":"Dane Tregeagle ,&nbsp;Catherine Doherty ,&nbsp;Timothy Callis,&nbsp;Michael Kassiou","doi":"10.1016/j.jphs.2025.04.004","DOIUrl":"10.1016/j.jphs.2025.04.004","url":null,"abstract":"<div><div>The ability to target the oxytocin and vasopressin receptors is of high therapeutic value due to their clinical relevance in wide range of neuropsychiatric conditions spanning from anxiety to schizophrenia. Despite the massive therapeutic potential in modulating this system, the only clinically approved small molecule-based therapeutics (Mozavaptan, Conivaptan and Tolvaptan) are for use in the periphery. Cyclotide mimetics of the native neuropeptides are well explored in the literature although these scaffolds are unsuitable for application to the central nervous system. This work highlights non-peptidic natural products that are active within the neurohypophysial system that may be used to inspire future drug discovery endeavours.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 238-258"},"PeriodicalIF":3.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931634","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
A novel lysophosphatidic acid receptor 1 antagonist with high brain penetrability has a curative effect in the empathic pain-related fibromyalgia model 一种新型高脑穿透性溶血磷脂酸受体1拮抗剂在共情性疼痛相关纤维肌痛模型中具有疗效
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-11 DOI: 10.1016/j.jphs.2025.03.012
Hiroyuki Neyama , Naoki Dozono , Yasuka Sahara , Kenji Nishikawa , Hiroshi Ueda
{"title":"A novel lysophosphatidic acid receptor 1 antagonist with high brain penetrability has a curative effect in the empathic pain-related fibromyalgia model","authors":"Hiroyuki Neyama ,&nbsp;Naoki Dozono ,&nbsp;Yasuka Sahara ,&nbsp;Kenji Nishikawa ,&nbsp;Hiroshi Ueda","doi":"10.1016/j.jphs.2025.03.012","DOIUrl":"10.1016/j.jphs.2025.03.012","url":null,"abstract":"<div><div>Lysophosphatidic acid receptor 1 (LPA<sub>1</sub>) plays a pivotal role in the pathophysiology of various diseases, especially chronic pain. In this study, we assessed the biochemical properties of Compound A, a novel LPA<sub>1</sub> antagonist and its beneficial effects in the fibromyalgia (FM)-like pain model. Compound A was found to be a high-affinity and selective LPA<sub>1</sub> antagonist and have high brain penetrability. Repeated oral administrations of Compound A reversed the hyperalgesia as late as 9 days after the treatments, suggesting this compound has a curative effect in the FM model.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 139-142"},"PeriodicalIF":3.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825549","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
Rosamultin attenuates cerebral ischemia/reperfusion injury by inhibiting autophagy via the PI3K/Akt/mTOR pathway Rosamultin通过PI3K/Akt/mTOR通路抑制自噬,减轻脑缺血/再灌注损伤
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-08 DOI: 10.1016/j.jphs.2025.04.001
Hailin Zhang , Baoyuan Zhou , Jixing Liu , Bo Tang , Zongzhi Xie , Jianxiong Li
{"title":"Rosamultin attenuates cerebral ischemia/reperfusion injury by inhibiting autophagy via the PI3K/Akt/mTOR pathway","authors":"Hailin Zhang ,&nbsp;Baoyuan Zhou ,&nbsp;Jixing Liu ,&nbsp;Bo Tang ,&nbsp;Zongzhi Xie ,&nbsp;Jianxiong Li","doi":"10.1016/j.jphs.2025.04.001","DOIUrl":"10.1016/j.jphs.2025.04.001","url":null,"abstract":"<div><div>Rosamultin (Rosa), a natural small-molecule compound, is known for its protective activity against hypoxia-induced injury, but its role in cerebral ischemic stroke injury remains unclear. To assess Rosa's effects on cerebral ischemic stroke, the intraluminal filament method was used to construct the middle cerebral artery occlusion and reperfusion (MCAO) in vivo model with 1 h occlusion and 48 h reperfusion. In addition, an oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro model was constructed using HT22 cells. The protective role and underlying mechanism of Rosa on cell injury was also determined in vivo and in vitro. Rosa notably inhibited neurological deficits and diminished infarct volume and neuronal apoptosis in mice exposed to MCAO. Rosa also exerted neuroprotection in the OGD/R model by improving cell viability, decreasing apoptosis, and enhancing the p-Akt and p-mTOR levels. However, <span>LY294002</span>, a PI3K inhibitor, restored the beneficial influences of Rosa after OGD/R. Moreover, Rosa treatment inhibited autophagy levels, and <span>LY294002</span> partially restored the inhibition of autophagy levels caused by Rosa in the OGD/R model. In addition, Rosa enhanced the p-Akt and p-mTOR levels and inhibited autophagy levels in mice after MCAO. Rosa could attenuate autophagy via activating the PI3K/Akt/mTOR axis, thereby alleviating cerebral ischemia stroke injury.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 182-192"},"PeriodicalIF":3.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864011","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
Clarifying the mechanism of astaxanthin in the treatment of inflammation in ischemic stroke using integrated network analysis 应用综合网络分析阐明虾青素治疗缺血性脑卒中炎症的作用机制
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-08 DOI: 10.1016/j.jphs.2025.04.003
Jinwen Yao , Xu Wang , Dexi Zhao
{"title":"Clarifying the mechanism of astaxanthin in the treatment of inflammation in ischemic stroke using integrated network analysis","authors":"Jinwen Yao ,&nbsp;Xu Wang ,&nbsp;Dexi Zhao","doi":"10.1016/j.jphs.2025.04.003","DOIUrl":"10.1016/j.jphs.2025.04.003","url":null,"abstract":"<div><h3>Background and objective</h3><div>Ischemic stroke is a disease with high incidence. Astaxanthin is a functional foods with protective effects against ischemic stroke. However, the integral mechanism of astaxanthin protect ischemic stroke is not clear. The aim of this study was to investigate the mechanism of astaxanthin protect ischemic stroke by integrated network analysis.</div></div><div><h3>Methods</h3><div>Middle cerebral artery occlusion model was used to establish ischemic stroke model, and ischemic stroke models were treated with 25, 45, 65 mg/kg astaxanthin for 7 days. The rats were killed 24 h after successful modeling. Integrated network analysis, molecular docking, molecular dynamics (MD) simulation, and Western blot were used to explore the astaxanthin and potential proteins related to inflammation and cell death.</div></div><div><h3>Results</h3><div>The results of integrated network analysis indicate that astaxanthin may protect ischemic stroke through Toll like receptor signaling pathway and apoptosis pathway. The main targets involved MMP9, IL1B, IL10, Bcl2 and among others. astaxanthin has a low binding score and compact complex with PARP1, AIF, Bax, IL10, MMP9, Bcl2. In addition, astaxanthin has reduced inflammation and cell death-related proteins such as PARP1, AIF, Bax, TLR4, MMP9, IL1β and increased anti-inflammation and anti-cell death-related proteins by Bcl2 and IL10.</div></div><div><h3>Conclusions</h3><div>Astaxanthin can improve anti-inflammatory, anti-cell death ability after ischemic stroke. Our study provides a theoretical basis for the subsequent experimental and clinical application of astaxanthin in the treatment of ischemic stroke.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 3","pages":"Pages 155-165"},"PeriodicalIF":3.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864070","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
Hirsutine attenuated oxidative stress and autophagy in diabetic kidney disease through Keap1/Nrf2 pathway hirsutin通过Keap1/Nrf2通路减弱糖尿病肾病的氧化应激和自噬
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-07 DOI: 10.1016/j.jphs.2025.04.002
Yao Zhang , Bing Yang , Miao Tan, Jinchuan Tan
{"title":"Hirsutine attenuated oxidative stress and autophagy in diabetic kidney disease through Keap1/Nrf2 pathway","authors":"Yao Zhang ,&nbsp;Bing Yang ,&nbsp;Miao Tan,&nbsp;Jinchuan Tan","doi":"10.1016/j.jphs.2025.04.002","DOIUrl":"10.1016/j.jphs.2025.04.002","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the therapeutic potential and renal protective mechanisms of hirsutine in diabetic kidney disease (DKD).</div></div><div><h3>Methods</h3><div>A DKD model was induced in Sprague-Dawley rats using a high-fat diet (HFD) and streptozotocin (STZ). High glucose (HG)-stimulated HK-2 cells served as an <em>in vitro</em> model. Reactive oxygen species (ROS) levels in kidney tissues were measured using dihydroethidium (DHE) staining. ELISA was performed to measure MDA, SOD, and GSH in both rat tissues and HK-2 cells. Western blot and immunofluorescence analyses evaluated renal fibrosis, the Nrf2 signaling pathway, and autophagy-related proteins (Beclin 1, LC3I/II, P62).</div></div><div><h3>Results</h3><div>Hirsutine treatment significantly improved metabolic and renal parameters in rats, enhancing renal function and reducing fibrosis, as shown by lower levels of Vimentin, Collagen-IV, and α-SMA. It alleviated oxidative stress, indicated by reduced ROS and MDA levels and increased SOD and GSH activity. Additionally, hirsutine enhanced autophagy, reflected by higher Beclin 1 and LC3I/II levels and decreased P62 expression. By disrupting the Keap1-Nrf2 interaction, hirsutine increased Nrf2 levels and upregulated antioxidative enzymes like NQO1, SOD-2, and HO-1.</div></div><div><h3>Conclusion</h3><div>Hirsutine exhibited renoprotective effects in DKD by modulating the Keap1/Nrf2 pathway, mitigating oxidative stress and promoting autophagy, making it a promising candidate for treatment.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 143-153"},"PeriodicalIF":3.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828878","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
Ramelteon coordinates theta and gamma oscillations in the hippocampus for novel object recognition memory in mice Ramelteon在小鼠的新物体识别记忆中协调海马中的θ和γ振荡
IF 3 3区 医学
Journal of pharmacological sciences Pub Date : 2025-04-01 DOI: 10.1016/j.jphs.2025.03.013
Kinjiro Takeda , Kisa Watanabe , Sena Iijima , Takeshi Nagahiro , Haruka Suzuki , Kano Izumo , Yuji Ikegaya , Nobuyoshi Matsumoto
{"title":"Ramelteon coordinates theta and gamma oscillations in the hippocampus for novel object recognition memory in mice","authors":"Kinjiro Takeda ,&nbsp;Kisa Watanabe ,&nbsp;Sena Iijima ,&nbsp;Takeshi Nagahiro ,&nbsp;Haruka Suzuki ,&nbsp;Kano Izumo ,&nbsp;Yuji Ikegaya ,&nbsp;Nobuyoshi Matsumoto","doi":"10.1016/j.jphs.2025.03.013","DOIUrl":"10.1016/j.jphs.2025.03.013","url":null,"abstract":"<div><div>Object recognition memory is an animal's ability to discriminate between novel and familiar items and is supported by neural activities in not only the perirhinal cortex but also the hippocampus and prefrontal cortex. Since we previously demonstrated that ramelteon enhanced object recognition memory in mice, we sought neural correlates of the memory improvement. We recorded neural activity in the hippocampus and prefrontal cortex of mice while they performed a novel object recognition task. We found that theta oscillations in the hippocampus were enhanced when ramelteon-treated mice explored both novel and familiar objects. Moreover, we showed high coherence in phases at low gamma frequencies between the hippocampus and prefrontal cortex. We assume that theta enhancement is indicative of increased cholinergic activity by melatonin receptor activation. High coherence of low gamma oscillations between the hippocampal and prefrontal network in ramelteon-treated mice sampling novel objects suggests better cognitive operations for discrimination between novelty and familiarity. The current study sheds light upon physiological consequences of melatonin receptor activation, further contributing improved cognitive functions.</div></div>","PeriodicalId":16786,"journal":{"name":"Journal of pharmacological sciences","volume":"158 2","pages":"Pages 121-130"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792004","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}
引用次数: 0
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