Xinye Yao, Yanbo Xue, Qiang Ma, Yajun Bai, Pu Jia, Yiman Zhang, Baochang Lai, Shuting He, Qiong Ma, Junbo Zhang, Hongyan Tian, Qian Yin, Xiaohui Zheng, Xiaopu Zheng
Pathological angiogenesis plays a major role in many disease processes, including cancer and diabetic retinopathy. Antiangiogenic therapy is a potential management for pathologic angiogenesis. The novel synthetic compound 221S-1a, derived from captopril, tanshinol and borneol, may have antiangiogenic properties. On the basis of MS, NMR and HPLC analysis, the structure of 221S-1a was identified. The cellular uptake and metabolism of this compound was also observed. Next, the antiangiogenic properties of 221S-1a were evaluated in tumor-xenograft and OIR models in vivo...
May 27, 2023: European Journal of Pharmacology
Xinyu Wang, Jiamin Zhang, Sisi Wang, Zhengyang Song, Hongxia Sun, Fangquan Wu, Xiaohui Lin, Keke Jin, Xiaofeng Jin, Wantie Wang, Qiongqiong Lin, Fangyan Wang
Ferroptosis was reported to be involved in cerebral ischemia-reperfusion injury (CIRI), on which the effects of berberine (BBR) remain unclear. Moreover, based on the critical role of gut microbiota in pleiotropic actions of BBR, we hypothesized that BBR can suppress CIRI-induced ferroptosis by modulating the gut microbiota. In this study, the results showed that BBR obviously attenuated the behavioral deficits of CIRI mice, accompanied with the improved survival rate and neuron damages, as phenocopied by dirty cage experiment...
May 26, 2023: European Journal of Pharmacology
Xianlong Ye, Yingli Chen, Jianying Qi, Shenglong Zhu, Yuanyuan Wu, Jingjing Xiong, Fei Hu, Zhimou Guo, Xinmiao Liang
Fibroblast growth factor 21 (FGF21) and glucagon-like peptide-1 (GLP-1) may be useful for the treatment of type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD). Previous studies have shown that GLP-1 may synergize with FGF21 in the regulation of glucose and lipid metabolism. Currently, no approved drug therapy is available for non-alcoholic steatohepatitis (NASH). Here, we constructed and screened dual-targeting fusion proteins of GLP-1 and FGF21, connected by elastin-like polypeptides (ELPs), to investigate whether a combination of these two hormones would have therapeutic effects in models of NASH...
May 26, 2023: European Journal of Pharmacology
Ahd A Atta, Weam W Ibrahim, Ahmed F Mohamed, Noha F Abdelkader
Fibromyalgia (FM) is a pain disorder marked by generalized musculoskeletal pain accompanied by depression, fatigue, and sleep disturbances. Galantamine (Gal) is a positive allosteric modulator of neuronal nicotinic acetylcholine receptors (nAChRs) and a reversible inhibitor of cholinesterase. The current study aimed to explore the therapeutic potential of Gal against reserpine (Res)-induced FM-like condition along with investigating the α7-nAChR's role in Gal-mediated effects. Rats were injected with Res (1 mg/kg/day; sc) for 3 successive days then Gal (5 mg/kg/day; ip) was given alone and with the α7-nAChR blocker methyllycaconitine (3 mg/kg/day; ip), for the subsequent 5 days...
May 26, 2023: European Journal of Pharmacology
Taslim B Shaikh, Madhusudhana Kuncha, Sai Balaji Andugulapati, Ramakrishna Sistla
In idiopathic pulmonary fibrosis (IPF), excessive collagen deposition predisposes to irreversible lung function decline, respiratory failure, and ultimately death. Due to the limited therapeutic efficacy of FDA-approved medications, novel drugs are warranted for better treatment outcomes. Dehydrozingerone (DHZ) is an analogue of curcumin that has been investigated against pulmonary fibrosis using a bleomycin-induced pulmonary fibrosis model in rats. In in vitro, TGF-β-induced differentiation models (NHLF, LL29, DHLF and A549 cells) were adopted to assess fibrotic markers expression and explored the mechanism of action...
May 26, 2023: European Journal of Pharmacology
Nanlin Zhu, Haonan Duan, Yingying Feng, Wenwei Xu, Jianhua Shen, Kai Wang, Jia Liu
Diabetic nephropathy (DN) is a major cause of renal failure and urgently necessitates new therapeutic strategies. Magnesium lithospermate B (MLB) showed a good protective effect on kidney injure by oral administration, despite its extremely low bioavailability. The current study aimed to investigate its gut microbiota-targeted mechanism to explain the paradoxical properties of pharmacodynamics and pharmacokinetics. Here we show that MLB alleviated DN by recovering the dysfunction of gut microbiota and their associated metabolites in colon content, such as short-chain fatty acids and amino acids...
May 26, 2023: European Journal of Pharmacology
Erick J Rodríguez-Palma, Isabel Velazquez-Lagunas, Ana Belen Salinas-Abarca, Guadalupe C Vidal-Cantú, María J Escoto-Rosales, Gabriela Castañeda-Corral, Alonso Fernández-Guasti, Vinicio Granados-Soto
Chronic stress affects millions of people around the world, and it can trigger different behavioral disorders like nociceptive hypersensitivity and anxiety, among others. However, the mechanisms underlaying these chronic stress-induced behavioral disorders have not been yet elucidated. This study was designed to understand the role of high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) in chronic stress-induced nociceptive hypersensitivity. Chronic restraint stress induced bilateral tactile allodynia, anxiety-like behaviors, phosphorylation of ERK and p38MAPK and activation of spinal microglia...
May 25, 2023: European Journal of Pharmacology
Hongcheng Jiang, Yue Jiang, Yunkun Qu, Jiagao Lv, Hesong Zeng
Thoracic aortic dissection (TAD) is common but lethal cardiovascular disease with high mortality. This study aimed to expound whether and how sGC-PRKG1 signaling pathway might promote the formation of TAD. Our work identified two modules with high relevance to TAD using WGCNA method. Combined with previous studies, we focused on the participation of endothelial NOS (eNOS) in the progression of TAD. Through immunohistochemistry, immunofluorescence and western blot we verified that eNOS expression was elevated in the tissues of patients and mice with aortic dissection, and the phosphorylation Ser1177 of eNOS was activated...
May 25, 2023: European Journal of Pharmacology
Shaimaa Maher, Mekki Bayachou, Pingfu Fu, Adonis Hijaz, Guiming Liu
Recent studies suggested smooth muscle contraction may involve mechanisms besides the myosin regulatory light chain (MLC) phosphorylation-induced actomyosin crossbridge cycling. This study aims to determine if focal adhesion kinase (FAK) activation is involved in mouse detrusor muscle contraction. The mouse detrusor muscle strips were preincubated with PF-573228 (2 μM), latrunculin B (1 μM), or the same volume of vehicle (DMSO) for 30 min. The contractile responses to KCl (90 mM), electrical field stimulation (EFS, 2-32 Hz), or carbachol (CCh, 10-7...
May 24, 2023: European Journal of Pharmacology
Soshi Narasaki, Soma Noguchi, Tomoaki Urabe, Kana Harada, Izumi Hide, Shigeru Tanaka, Yuki Yanase, Taketoshi Kajimoto, Kazue Uchida, Yasuo M Tsutsumi, Norio Sakai
Propofol is widely used for general anesthesia and sedation; however, the mechanisms of its anesthetic and adverse effects are not fully understood. We have previously shown that propofol activates protein kinase C (PKC) and induces its translocation in a subtype-specific manner. The purpose of this study was to identify the PKC domains involved in propofol-induced PKC translocation. The regulatory domains of PKC consist of C1 and C2 domains, and the C1 domain is subdivided into the C1A and C1B subdomains. Mutant PKCα and PKCδ with each domain deleted were fused with green fluorescent protein (GFP) and expressed in HeLa cells...
May 23, 2023: European Journal of Pharmacology
Yu-Wei Lai, Shih-Wei Wang, Chia-Liang Lin, Shiou-Sheng Chen, Kuan-Hung Lin, Yen-Tung Lee, Wei-Cheng Chen, Yi-Hsien Hsieh
Prostate cancer metastasis is associated with poor prognosis and is difficult to treat clinically. Numerous studies have shown that Asiatic Acid (AA) has antibacterial, anti-inflammatory, and antioxidant effects. However, the effect of AA on prostate cancer metastasis is still unclear. This purpose of this study is to investigate the effect of AA on prostate cancer metastasis and to better understand its molecular mechanisms of action. Our results indicate that AA ≤ 30 μM did not influence cell viability and cell cycle distribution in PC3, 22Rv1 and DU145 cells...
May 18, 2023: European Journal of Pharmacology
Warisara Parichatikanond, Ratchanee Duangrat, Supachoke Mangmool
Angiotensin II receptors are members of G protein-coupled receptor superfamily that manifest biased signals toward G protein- and β-arrestin-dependent pathways. However, the role of angiotensin II receptor-biased ligands and the mechanisms underlying myofibroblast differentiation in human cardiac fibroblasts have not been fully elucidated. Our results demonstrated that antagonism of angiotensin II type 1 receptor (AT1 receptor) and blockade of Gαq protein suppressed angiotensin II (Ang II)-induced fibroblast proliferation, overexpression of collagen I and α-smooth muscle actin (α-SMA), and stress fibre formation, indicating the AT1 receptor/Gαq axis is necessary for fibrogenic effects of Ang II...
May 18, 2023: European Journal of Pharmacology
Anita Yovas, Shervin Prince Stanely, Stanely Mainzen Prince Ponnian
The cardiac mitochondrial damage and cardiac hypertrophy pathways are intimately associated with the pathology of myocardial infarction (MI). The protective effects of β-caryophyllene on mitochondrial damage and cardiac hypertrophy pathways in isoproterenol-induced myocardial infarcted rats were investigated. Isoproterenol (100 mg/kg body weight) was administered to induce MI. The ST-segment, QT interval, and T wave were widened, and the QRS complex and P wave were shortened in the electrocardiogram (ECG) and the serum cardiac diagnostic markers and heart mitochondrial lipid peroxidation products, calcium ions, and reactive oxygen species (ROS) were elevated and the heart mitochondrial antioxidants, tricarboxylic acid cycle, and respiratory chain enzymes were lessened in isoproterenol-induced myocardial infarcted rats...
May 18, 2023: European Journal of Pharmacology
Hui Zhang, Laifa Wang, Bi Zhu, Yongping Yang, Chuanhai Cai, Xueqin Wang, Ling Deng, Binsheng He, Yanhui Cui, Wenhu Zhou
INTRODUCTION: DL-3-n-butylphthalide (NBP) and edaravone dexborneol (Eda-Dex) are two promising reagents for stroke treatment. However, the impacts of NBP and Eda-Dex on poststroke mental deficits are still poorly understood. In this study, we aimed to investigate and compare the influences of NBP and Eda-Dex on neurological function and cognitive behavior in rats with ischemic stroke. METHODS: An ischemic stroke model was established by middle cerebral artery occlusion (MCAO)...
May 17, 2023: European Journal of Pharmacology
Yuhki Ueda, Daisuke Uta, Hidemasa Furue, Yoshitaka Ohtubo
To evaluate the effects of antipruritic drugs, it is important to determine whether the neural responses induced by physiological itch stimuli are suppressed. Although there are several behavioral assessments for topical antipruritic drugs applied to the skin, there are few established methods at neuronal levels using in vivo electrophysiological recordings for predicting local efficacy of antipruritic drugs for cutaneous application. To establish an assessment of topical antipruritic drugs applied to skin using in vivo extracellular recording from neurons in the superficial dorsal horn, we examined the relationships between itch-related biting behavior and spinal neuronal responses elicited by intradermal injection of pruritogen serotonin (5-HT) in hairless mice...
May 17, 2023: European Journal of Pharmacology
Fan Zhang, Qianqian Li, Yaqin Zhang, Na Li, Mengjiao Rao, Shi Li, Zhiying Ai, Siyuan Yan, Zhichao Tian
As a key component of the COP9 signalosome complex, which participates in a variety of physiological processes, COPS3 is intimately related to multiple cancers. It promotes cell proliferation, progression and metastasis in several cancer cells. However, whether COPS3 participates in regulating anoikis, a specific kind of apoptosis and functions as an essential modulator of cell metastasis, has not yet been studied. Here, we found COPS3 is highly expressed in several cancers especially in osteosarcoma (OS). Overexpression of COPS3 promoted cell proliferation, cell viability and migration/invasion in both control cells and oxaliplatin (Oxa) treated cells...
May 16, 2023: European Journal of Pharmacology
Guangtang Chen, Zili Wang, Wenxue Song, Yidong Liao, Xudong Wang, Chen Chen, Jiang Ming, Junshuan Cui, Kaya Xu
PURPOSE: Every year, there is a large number of people take aspirin and atorvastatin to prevent ischemic stroke, but the effect of these drugs on gut microbiota remains unknown. We aimed to examine the effects of long-term regular oral aspirin with atorvastatin to prevent ischemic stroke on human gut microbiota. METHODS: A cross-sectional study of 20 participants with the drugs over one year and the other 20 gender- and age-matching participants without medication were recruited from the Affiliated Hospital of Guizhou Medical University...
May 16, 2023: European Journal of Pharmacology
Yunwei Li, Juan Wang, Lili Sun, Shengnan Zhu
No abstract text is available yet for this article.
May 15, 2023: European Journal of Pharmacology
Hanan S Althagafy, MostafaK Abd El-Aziz, Islam M Ibrahim, Esraa K Abd-Alhameed, EmadH M Hassanein
Nifuroxazide (NFX) is a safe nitrofuran antibacterial drug used clinically to treat acute diarrhea and infectious traveler diarrhea or colitis. Recent studies revealed that NFX displays multiple pharmacological effects, including anticancer, antioxidant, and anti-inflammatory effects. NFX has potential roles in inhibiting thyroid, breast, lung, bladder, liver, and colon cancers and osteosarcoma, melanoma, and others mediated by suppressing STAT3 as well as ALDH1, MMP2, MMP9, Bcl2 and upregulating Bax. Moreover, it has promising effects against sepsis-induced organ injury, hepatic disorders, diabetic nephropathy, ulcerative colitis, and immune disorders...
May 14, 2023: European Journal of Pharmacology
Qian Li, Yuan Fang, De-Wei Peng, Lu-An Li, Chun-Yu Deng, Hui Yang, Su-Juan Kuang, Qiao-Qiao Li, Meng-Zhen Zhang, Peng Zeng, Qian-Huan Zhang, Yang Liu, Hai Deng, Wei Wei, Yu-Mei Xue, Shu-Lin Wu, Fang Rao
AIM: Sacubitril/valsartan (Sac/Val, LCZ696), the world's first angiotensin receptor-neprilysin inhibitor (ARNi), has been widely used in the treatment of heart failure. However, the use of Sac/Val in the treatment of atrial fibrillation (AF), especially AF with hypertension, has been less reported. We investigated the effect of Sac/Val on atrial remodeling and hypertension-related AF. METHODS: The AF induction rate and electrophysiological characteristics of spontaneously hypertensive rats (SHRs) treated with Sac/Val or Val were detected by rapid atrial pacing and electrical mapping/optical mapping...
May 12, 2023: European Journal of Pharmacology
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