Distinct roles of the extracellular surface residues of glucagon-like peptide-1 receptor in β-arrestin 1/2 signaling
Eur J Pharmacol. 2024 Feb 13:176419. doi: 10.1016/j.ejphar.2024.176419. Online ahead of print.ABSTRACTGlucagon-like peptide-1 receptor (GLP-1R) is a prime drug target for type 2 diabetes and obesity. The ligand initiated GLP-1R interaction with G protein has been well studied, but not with β-arrestin 1/2. Therefore, bioluminescence resonance energy transfer (BRET), mutagenesis and an operational model were used to evaluate the roles of 85 extracellular surface residues on GLP-1R in β-arrestin 1/2 recruitment triggered by three representative GLP-1R agonists (GLP-1, exendin-4 and oxyntomodulin). Residues selectively regul...
Source: European Journal of Pharmacology - February 15, 2024 Category: Drugs & Pharmacology Authors: Saifei Lei Qian Meng Yanyun Liu Qiaofeng Liu Antao Dai Xiaoqing Cai Ming-Wei Wang Qingtong Zhou Hu Zhou Dehua Yang Source Type: research
Distinct roles of the extracellular surface residues of glucagon-like peptide-1 receptor in β-arrestin 1/2 signaling
Eur J Pharmacol. 2024 Feb 13:176419. doi: 10.1016/j.ejphar.2024.176419. Online ahead of print.ABSTRACTGlucagon-like peptide-1 receptor (GLP-1R) is a prime drug target for type 2 diabetes and obesity. The ligand initiated GLP-1R interaction with G protein has been well studied, but not with β-arrestin 1/2. Therefore, bioluminescence resonance energy transfer (BRET), mutagenesis and an operational model were used to evaluate the roles of 85 extracellular surface residues on GLP-1R in β-arrestin 1/2 recruitment triggered by three representative GLP-1R agonists (GLP-1, exendin-4 and oxyntomodulin). Residues selectively regul...
Source: European Journal of Pharmacology - February 15, 2024 Category: Drugs & Pharmacology Authors: Saifei Lei Qian Meng Yanyun Liu Qiaofeng Liu Antao Dai Xiaoqing Cai Ming-Wei Wang Qingtong Zhou Hu Zhou Dehua Yang Source Type: research
Ruxolitinib attenuates microglial inflammatory response by inhibiting NF- κB/MAPK signaling pathway
Eur J Pharmacol. 2024 Feb 12:176403. doi: 10.1016/j.ejphar.2024.176403. Online ahead of print.ABSTRACTNeuroinflammation is involved in the physiological and pathological processes of numerous neurological diseases, and its inhibition seems to be a promising therapeutic direction for these diseases. Ruxolitinib is a classical Janus kinase (JAK) inhibitor that is oral, highly potent and bioavailable, which has recently gained approval from the US Food and Drug Administration (FDA) for the treatment of inflammatory disorders. The potential inhibitory effect of ruxolitinib on neuroinflammation has not been fully studied. In th...
Source: European Journal of Pharmacology - February 14, 2024 Category: Drugs & Pharmacology Authors: Jingli Min Hongmei Zheng Heye Xia Xuejun Tian Meihao Liang Jing Zhang Wenhai Huang Source Type: research
Ruxolitinib attenuates microglial inflammatory response by inhibiting NF- κB/MAPK signaling pathway
Eur J Pharmacol. 2024 Feb 12:176403. doi: 10.1016/j.ejphar.2024.176403. Online ahead of print.ABSTRACTNeuroinflammation is involved in the physiological and pathological processes of numerous neurological diseases, and its inhibition seems to be a promising therapeutic direction for these diseases. Ruxolitinib is a classical Janus kinase (JAK) inhibitor that is oral, highly potent and bioavailable, which has recently gained approval from the US Food and Drug Administration (FDA) for the treatment of inflammatory disorders. The potential inhibitory effect of ruxolitinib on neuroinflammation has not been fully studied. In th...
Source: European Journal of Pharmacology - February 14, 2024 Category: Drugs & Pharmacology Authors: Jingli Min Hongmei Zheng Heye Xia Xuejun Tian Meihao Liang Jing Zhang Wenhai Huang Source Type: research
Licochalcone A induces mitochondria-dependent apoptosis and interacts with venetoclax in acute myeloid leukemia
Eur J Pharmacol. 2024 Feb 11:176418. doi: 10.1016/j.ejphar.2024.176418. Online ahead of print.ABSTRACTThe management of patients with acute myeloid leukemia (AML) remains a challenge because of the complexity and heterogeneity of this malignancy. Despite the recent approval of several novel targeted drugs, resistance seems inevitable, and clinical outcomes are still suboptimal. Increasing evidence supports the use of natural plants as an important source of anti-leukemic therapeutics. Licochalcone A (LCA) is an active flavonoid isolated from the roots of licorice, Glycyrrhiza uralensis Fisch., possessing extensive anti-tum...
Source: European Journal of Pharmacology - February 13, 2024 Category: Drugs & Pharmacology Authors: Youhong Li Mengting Zhao Ye Lin Xia Jiang Lili Jin Peipei Ye Ying Lu Renzhi Pei Lei Jiang Source Type: research
Gabapentin attenuates cardiac remodeling after myocardial infarction by inhibiting M1 macrophage polarization through the peroxisome proliferator-activated receptor- γ pathway
CONCLUSION: Gabapentin attenuates cardiac remodeling by inhibiting inflammation via peroxisome proliferator-activated receptor-γ activation and preventing calcium overload.PMID:38350591 | DOI:10.1016/j.ejphar.2024.176398 (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - February 13, 2024 Category: Drugs & Pharmacology Authors: Zhenjun Li Shaoxian Wang Ying Qin Bo Yang Chengcheng Wang Tianyi Lu Jie Xu Lige Zhu Chen Yuan Wei Han Source Type: research
Palmatine alleviates cardiac fibrosis by inhibiting fibroblast activation through the STAT3 pathway
This study investigated the potential therapeutic value and mechanism of palmatine against cardiac fibrosis. Adult male C57BL/6 mice were treated with vehicle, isoproterenol (ISO), or ISO plus palmatine for one week. After echocardiography assessment, mice hearts were collected for histopathology, real-time polymerase chain reaction, and Western blot analyses. Primary rat CFs were utilized in vitro. Compared to control, ISO-treated mice exhibited cardiac hypertrophy and structural abnormalities; however, treatment with palmatine ameliorated these effects of ISO. Moreover, palmatine treatment mitigated ISO-induced cardiac f...
Source: European Journal of Pharmacology - February 13, 2024 Category: Drugs & Pharmacology Authors: Shaoling Lin Shengxi Zhang Angyu Zhan Jiaojiao Feng Qianqian Yang Tongjun Li Zijian Liu Quqian Mo Hui Fan Keke Wang Lexun Wang Source Type: research
PARP-1 inhibitor alleviates cerebral ischemia/reperfusion injury by reducing PARylation of HK-1 and LDH in mice
Eur J Pharmacol. 2024 Feb 10:176377. doi: 10.1016/j.ejphar.2024.176377. Online ahead of print.ABSTRACTPoly (ADP-ribose) polymerase-1 (PARP-1) activity significantly increases during cerebral ischemia/reperfusion. PARP-1 is an NAD+-consumption enzyme. PARP-1 hyperactivity causes intracellular NAD+ deficiency and bioenergetic collapse, contributing to neuronal death. Besides, the powerful trigger of PARP-1 causes the catalyzation of poly (ADP-ribosyl)ation (PARylation), a posttranslational modification of proteins. Here, we found that PARP-1 was activated in the ischemic brain tissue during middle-cerebral-artery occlusion a...
Source: European Journal of Pharmacology - February 12, 2024 Category: Drugs & Pharmacology Authors: Ya-Ling Chen Yi Wang Qiu-Yu Fang Tong Wang Cong Chen Tong-Yao Gao Ming Wu Wei-Ping Zhang Yun-Bi Lu Source Type: research
Tet1/DLL3/Notch1 signal pathway affects hippocampal neurogenesis and regulates depression-like behavior in mice
In this study, the chronic social defeat stress (CSDS) paradigm was constructed by overexpressing Tet1 protein in the mouse hippocampus, and 5-ethynyl-2'-deoxyuridine (EdU, 50 mg/kg) was injected on the seventh day to explore the mechanism of the regulation of the Tet1/Delta-like protein 3 (DLL3)/Notch1 protein pathway in mice hippocampal neurogenesis and its influence on depression-like behaviour. Following CSDS, the expression level of Tet1 decreased significantly. Moreover, due to the downregulation of Tet1 protein, the maintenance of the DNA methylation and demethylation balance was affected, resulting in a significant...
Source: European Journal of Pharmacology - February 12, 2024 Category: Drugs & Pharmacology Authors: Ruonan Shuang Tiantian Gao Zhongwen Sun Yue Tong Keke Zhao Hanqing Wang Source Type: research
Effect of ABT-639 on Cav3.2 channel activity and its analgesic actions in mouse models of inflammatory and neuropathic pain
Eur J Pharmacol. 2024 Feb 9:176416. doi: 10.1016/j.ejphar.2024.176416. Online ahead of print.ABSTRACTCav3.2 T-type calcium channels are important targets for pain relief in rodent models of inflammatory and neuropathic pain. Even though many T-type channel blockers have been tested in mice, only one molecule, ABT-639, has been tested in phase II clinical studies and did not produce analgesic effects over placebo. Here we examined the effects of ABT-639 on Cav3.2 channel activity in tsA-201 cells and dorsal root ganglion (DRG) neurons, in comparison with another established Cav3.2 inhibitor Z944. These experiments revealed ...
Source: European Journal of Pharmacology - February 11, 2024 Category: Drugs & Pharmacology Authors: Flavia Tasmin Techera Antunes Sun Huang Lina Chen Gerald W Zamponi Source Type: research
Contribution of chemical and electrical transmission to the low delta-like intrinsic retinal oscillation in mice: A role for daylight-activated neuromodulators
Eur J Pharmacol. 2024 Feb 9:176384. doi: 10.1016/j.ejphar.2024.176384. Online ahead of print.ABSTRACTBasal electroretinogram (ERG) oscillations have shown predictive value for modifiable risk factors for type 2 diabetes. However, their origin remains unknown. Here, we seek to establish the pharmacological profile of the low delta-like (δ1) wave in the mouse because it shows light sensitivity in the form of a decreased peak frequency upon photopic exposure. Applying neuropharmacological drugs by intravitreal injection, we eliminated the δ1 wave using lidocaine or by blocking all chemical and electrical synapses. The δ1 w...
Source: European Journal of Pharmacology - February 11, 2024 Category: Drugs & Pharmacology Authors: Pamela Reyes-Ortega Alejandra Rodr íguez-Arzate Rams és Noguez-Imm Edith Arnold St éphanie C Thébault Source Type: research
Mechanisms underlying the efficacy and limitation of dopa and tetrahydrobiopterin therapies for the deficiency of GTP cyclohydrolase 1 revealed in a novel mouse model
In this study, we tested the efficacy of dopa and BH4 therapies by using a novel GTPCH deficiency mouse model, Gch1KI/KI, which manifested infancy-onset motor deficits and growth retardation similar to the patients. First, dopa supplementation supported Gch1KI/KI mouse survival to adulthood, but residual motor deficits and dwarfism remained. Interestingly, RNAseq analysis indicated that while the genes participating in BH4 biosynthesis and regeneration were significantly increased in the liver, no significant changes were observed in the brain. Second, BH4 supplementation alone restored the growth of Gch1KI/KI pups only in...
Source: European Journal of Pharmacology - February 11, 2024 Category: Drugs & Pharmacology Authors: Xiaoling Jiang Yongxian Shao Yongqiang Liao Xiaoning Zheng Minzhi Peng Yanna Cai Meiyi Wang Huazhen Liu Chunhua Zeng Yunting Lin Wen Zhang Li Liu Source Type: research
Catalpol alleviates hypoxia ischemia-induced brain damage by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis in neonatal rats
This study examined the neuroprotective effects of catalpol using a neonatal rat HIE model and found that catalpol might protect the brain through inhibiting neuronal ferroptosis and ameliorating oxidative stress. Behavior tests suggested that catalpol treatment improved functions of motor, learning, and memory abilities after hypoxic-ischemic injury. Catalpol treatment inhibited changes to several ferroptosis-related proteins, including p-PI3K, p-AKT, NRF2, GPX4, SLC7A11, SLC3A2, GCLC, and GSS in HIE neonatal rats. Catalpol also prevented changes to several ferroptosis-related proteins in PC12 cells after oxygen-glucose d...
Source: European Journal of Pharmacology - February 10, 2024 Category: Drugs & Pharmacology Authors: Jingjing Lin Lu Deng Ailin Qi Hong Jiang Di Xu Yuehui Zheng Zixuan Zhang Xiaoman Guo Beilei Hu Peijun Li Source Type: research
Canagliflozin protects against hyperglycemia-induced cerebrovascular injury by preventing blood-brain barrier (BBB) disruption via AMPK/Sp1/adenosine A2A receptor
Eur J Pharmacol. 2024 Feb 8:176381. doi: 10.1016/j.ejphar.2024.176381. Online ahead of print.ABSTRACTDiabetes mellitus causes brain microvascular endothelial cell (MEC) damage, inducing dysfunctional angiogenic response and disruption of the blood-brain barrier (BBB). Canagliflozin is a revolutionary hypoglycemic drug that exerts neurologic and/or vascular-protective effects beyond glycemic control; however, its underlying mechanism remains unclear. In the present study, we hypothesize that canagliflozin ameliorates BBB permeability by preventing diabetes-induced brain MEC damage. Mice with high-fat diet/streptozotocin-ind...
Source: European Journal of Pharmacology - February 10, 2024 Category: Drugs & Pharmacology Authors: Zhiyi Liu Wei Hua Sinan Jin Yueying Wang Yuxin Pang Benshuai Wang Nan Zhao Jiping Qi Yuejia Song Source Type: research
5- methylcytidine effectively improves spermatogenesis recovery in busulfan-induced oligoasthenospermia mice
In this study, we made a mouse model of oligoasthenospermia through the administration of busulfan (BUS). For the first time, we demonstrated that m5C levels decreased in oligoasthenospermia. The m5C levels were upregulated through the treatments of 5-methylcytidine. The testicular morphology and sperm concentrations were improved via upregulating m5C. The cytoskeletal regenerations of testis and sperm were accompanying with m5C treatments. m5C treatments improved T levels and reduced FSH and LH levels. The levels of ROS and MDA were significantly reduced through m5C treatments. RNA sequencing analysis showed m5C treatment...
Source: European Journal of Pharmacology - February 10, 2024 Category: Drugs & Pharmacology Authors: Chengniu Wang Taowen Ye Junze Bao Jin Dong Wenran Wang Chunhong Li Hongping Ding Hanqing Chen Xiaorong Wang Jianwu Shi Source Type: research
