Factor Xa inhibition by rivaroxaban attenuates cardiac remodeling due to intermittent hypoxia
This study investigated the influence of rivaroxaban on cardiac remodeling caused by intermittent hypoxia (IH). Male C57BL/6J mice were exposed to IH (repeated cycles of 5% oxygen for 1.5 min followed by 21% oxygen for 5 min) for 28 days with/without rivaroxaban (12 mg/kg/day) or FSLLRY, a protease-activated receptor (PAR)-2 antagonist (10 μg/kg/day). IH caused endothelial cell degeneration in the small arteries of the right atrial myocardium and increased the level of %fibrosis and 4-hydroxy-2-nonenal protein adducts in the left ventricular myocardium. IH also increased the expression of PAR-2 as we...
Source: Journal of Pharmacological Sciences - July 19, 2018 Category: Drugs & Pharmacology Source Type: research

T-type calcium channel enhancer SAK3 produces anti-depressant-like effects by promoting adult hippocampal neurogenesis in olfactory bulbectomized mice
Publication date: Available online 17 July 2018Source: Journal of Pharmacological SciencesAuthor(s): Jing Xu, Yasushi Yabuki, Mengze Yu, Kohji FukunagaAbstractT-type calcium channels are involved in the pathophysiology of epilepsy, pain, and sleep. Recently, we developed a novel spiroimidazopyridine compound, SAK3 (ethyl 8'-methyl-2', 4-dioxo-2-(piperidin-1-yl)-2'H-spiro [cyclopentane-1,3'-imidazo [1,2-a] pyridine]-2-ene-3-carboxylate), which enhances T-type calcium channel currents and improves memory deficits in olfactory bulbectomized (OBX) mice. Here, we demonstrated the anti-depressant effects of SAK3 in OBX mice. Chr...
Source: Journal of Pharmacological Sciences - July 18, 2018 Category: Drugs & Pharmacology Source Type: research

A quinoline-based FtsZ inhibitor for the study of antimicrobial activity and synergistic effects with β-lactam antibiotics
Publication date: Available online 17 July 2018Source: Journal of Pharmacological SciencesAuthor(s): Zhiyuan Fang, Li Ban, Yanan Li, Wenchang Yuan, Zhihua Liu, Ting Liu, Xiaomei Li, Kwok-yin Wong, Yujing Lu, Ning Sun, Xingang YaoAbstractThe antibacterial activity and the synergistic effect with β-lactam antibiotics of a new 1-methylquinolinium iodide derivative were investigated. The experimental results indicate that the compound possesses a strong antibacterial activity against a panel of bacteria including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and NDM-1 Escherichia coli with...
Source: Journal of Pharmacological Sciences - July 18, 2018 Category: Drugs & Pharmacology Source Type: research

Inhibition of nuclear factor-κB p65 phosphorylation by 3,4-dihydroxybenzalacetone and caffeic acid phenethyl ester
Publication date: Available online 10 July 2018Source: Journal of Pharmacological SciencesAuthor(s): Ken Takakura, Shouhei Takatou, Ryoichi Tomiyama, Thuong Manh Le, Dinh Thi Nguyen, Yutaka Nakamura, Tetsuya Konishi, Seiichi Matsugo, Osamu HoriAbstract3,4-Dihydroxybenzalacetone (DBL) and caffeic acid phenethyl ester (CAPE) are both catechol-containing phenylpropanoid derivatives with various bioactivities. In the present study, we compared the effects of these compounds and other phenylpropanoid derivatives on the activation of nuclear factor-κB (NF-κB) signaling, a major pathway in the inflammatory response, u...
Source: Journal of Pharmacological Sciences - July 11, 2018 Category: Drugs & Pharmacology Source Type: research

Discovery of a potent hedgehog pathway inhibitor capable of activating caspase8-dependent apoptosis
Publication date: Available online 10 July 2018Source: Journal of Pharmacological SciencesAuthor(s): Qin Chen, Haoran Zhang, Meng Wu, Qin Wang, Lusong Luo, Haikuo Ma, Xiaohu Zhang, Sudan HeAbstractAberrant activation of Hedgehog (Hh) signaling is associated with the development of numerous human cancers. Vismodegib is the first Hh inhibitor approved for anti-cancer therapy by targeting Smoothened (SMO), a critical regulator of the Hh pathway. However, acquisition of drug resistance to vismodegib occurs overtime. Apoptosis is a prevalent form of programmed cell death that is executed by caspases. Induction of tumor cell apo...
Source: Journal of Pharmacological Sciences - July 11, 2018 Category: Drugs & Pharmacology Source Type: research

Mangiferin inhibits High-Fat Diet induced vascular injury via regulation of PTEN/AKT/eNOS pathway
Publication date: Available online 10 July 2018Source: Journal of Pharmacological SciencesAuthor(s): Jiang Fang, Zhang De-long, Jia Min, Hao Wei-hua, Li Yong-junAbstractMangiferin (MAN), a naturally occurring polyphenol commonly found in mango and papaya. However, little is known its anti-vascular injury effects and the underlying mechanisms. This paper investigated the anti-vascular injury effect of MAN and the mechanisms in high-fat diet (HFD)-induced C57BL/6J mice and oxidized low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells (HUVECs). The levels of plasma lipid, inflammatory factors and ni...
Source: Journal of Pharmacological Sciences - July 11, 2018 Category: Drugs & Pharmacology Source Type: research

Bakuchiol exhibits anti-metastasis activity through NF-κB cross-talk signaling with AR and ERβ in androgen-independent prostate cancer cells PC-3
Publication date: Available online 16 June 2017Source: Journal of Pharmacological SciencesAuthor(s): Lin Miao, Xiaoting Yun, Rui Tao, Yuefei Wang, Xiumei Gao, Guanwei Fan, Yan Zhu, Ting Cai, Zhipeng Zhu, Chunlin YanAbstractAndrogen-independent prostate cancer (PCa) is a developed tumor derived from the local androgen dependent PCa, which often affects elderly men. Psoralea corylifolia L, a traditional Chinese medicine, has been widely used for PCa treatment as an important part of a common prescription, while the mechanism remains unclear. Our study was aimed to investigate the tumor-inhibitory effect of its main component...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Effect of a SGLT2 inhibitor on the systemic and intrarenal renin–angiotensin system in subtotally nephrectomized rats
Publication date: Available online 28 October 2017Source: Journal of Pharmacological SciencesAuthor(s): Lei Li, Yoshio Konishi, Takashi Morikawa, Yifan Zhang, Chizuko Kitabayashi, Hideki Kobara, Tsutomu Masaki, Daisuke Nakano, Hirofumi Hitomi, Hiroyuki Kobori, Akira NishiyamaAbstractWe aimed to examine the effects of a sodium glucose co-transporter 2 (SGLT2) inhibitor on systemic and intrarenal renin–angiotensin system (RAS) in subtotally nephrectomized non-diabetic rats, a model of chronic kidney disease (CKD). Oral administration of the selective SGLT2 inhibitor, TA-1887 (10 mg/kg/day), for 10 weeks induced gl...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Punicalagin suppresses methicillin resistance of Staphylococcus aureus to oxacillin
Publication date: Available online 27 December 2017Source: Journal of Pharmacological SciencesAuthor(s): Su-Hyun Mun, Ok-Hwa Kang, Ryong Kong, Tian Zhou, Sang-A. Kim, Dong-Yeul KwonAbstractMethicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that is cross-resistant to most β-lactam antibiotics. We investigated whether oxacillin, which is a β-lactam antibiotic, alone or in combination with punicalagin can affect the penicillin binding protein 2a (PBP2a)-mediated resistance of MRSA. Susceptibility testing of punicalagin with oxacillin was performed using the microdilution and checkerboa...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Effect of repeated oral administration of chondroitin sulfate on neuropathic pain induced by partial sciatic nerve ligation in mice
We examined whether chondroitin sulfate (CS), a compound used to treat osteoarthritis and joint pain, is effective against partial sciatic nerve ligation (PSNL)-induced neuropathic pain. Repeated oral administration of CS (300 mg/kg, b.i.d. for 20 days) resulted in inhibition of tactile allodynia observed 21 days after PSNL. On day 21, phosphorylation of spinal p38 mitogen-activated protein kinase (MAPK) was attenuated by CS. CS also inhibited c-Fos upregulation in ipsilateral deep dorsal horn (laminae III–IV) neurons, which receive Aβ-fiber afferent inputs. These findings suggest that CS attenuates PSNL-in...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Modafinil alleviates levodopa-induced excessive nighttime sleepiness and restores monoaminergic systems in a nocturnal animal model of Parkinson's disease
Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Rina Ando, Mohammed Emamussalehin Choudhury, Yuki Yamanishi, Win Thiri Kyaw, Madoka Kubo, Mariko Kannou, Noriko Nishikawa, Junya Tanaka, Masahiro Nomoto, Masahiro NagaiAbstractTreatment with dopaminergic agents result excessive daytime sleepiness (EDS) and some studies have shown the benefit of using modafinil for treating excessive daytime sleepiness of Parkinson's disease (PD) patient. We investigated whether modafinil have ameliorative properties against levodopa induced excessive nighttime sleepiness (ENS) in MPTP-tre...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Matrix Gla protein negatively regulates calcification of human aortic valve interstitial cells isolated from calcified aortic valves
In this study, we investigated the role of matrix Gla protein (MGP), a known calcification inhibitor that antagonizes bone morphogenetic protein 2 (BMP2) in TNF-α-induced calcification of HAVICs. HAVICs isolated from aortic valves were cultured, and calcification was significantly induced with 30 ng/mL TNF-α. Gene expression of the calcigenic marker, BMP2, was significantly increased in response to TNF-α, while the gene and protein expression of MGP was strongly decreased. To confirm the role of MGP, MGP-knockdown HAVICs and HAVICs overexpressing MGP were generated. In HAVICs, in which MGP expression...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Proarrhythmia risk prediction using human induced pluripotent stem cell-derived cardiomyocytes
Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Daiju Yamazaki, Takashi Kitaguchi, Masakazu Ishimura, Tomohiko Taniguchi, Atsuhiro Yamanishi, Daisuke Saji, Etsushi Takahashi, Masao Oguchi, Yuta Moriyama, Sanae Maeda, Kaori Miyamoto, Kaoru Morimura, Hiroki Ohnaka, Hiroyuki Tashibu, Yuko Sekino, Norimasa Miyamoto, Yasunari KandaAbstractHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are expected to become a useful tool for proarrhythmia risk prediction in the non-clinical drug development phase. Several features including electrophysiological prope...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Akebia saponin D alleviates hepatic steatosis through BNip3 induced mitophagy
Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Li-li Gong, Song Yang, Wen Zhang, Fei-fei Han, Ya-li Lv, Zi-Rui Wan, He Liu, Yang-jie Jia, Ling-ling Xuan, Li-hong LiuAbstractAkebia Saponin D (ASD) is the most abundant constituent of the rhizome of Dipsacus asper Wall. The prior studies have shown that ASD alleviates hepatic steatosis targeted at the modulation of autophagy and exerts hepatoprotective effects through mitochondria. However, it is still unclear which signal transduction pathway that ASD increase autophagy and protect the mitochondria. The purpose of this ...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Effects of moxifloxacin on the proarrhythmic surrogate markers in healthy Filipino subjects: Exposure-response modeling using ECG data of thorough QT/QTc study
Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Suchitra Matsukura, Yuji Nakamura, Kiyotaka Hoshiai, Takashi Hayashi, Tadashi Koga, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T. Naito, Atsushi SugiyamaAbstractEffects of moxifloxacin on QTc as well as proarrhythmic surrogate markers including J-Tpeakc, Tpeak-Tend and short-term variability (STV) of repolarization were examined by using both standard E14 time-based evaluation and exposure-response modeling. The study was conducted with a single-blind, r...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice
In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show si...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Up-regulation of microRNA-93 inhibits TGF-β1-induced EMT and renal fibrogenesis by down-regulation of Orai1
In this study, our data showed that miR-93 was dramatically decreased in renal tissues of patients with DN and TGF-β1-stimulated HK2 cells. Moreover, the decreased level of miR-93 was closely associated with the increased expression of Orai1. Overexpression of miR-93 decreased Orai1 expression, and then suppressed TGF-β1-mediated EMT and fibrogenesis. Next, we predicted that the Orai1 was a potential target gene of miR-93, and demonstrated that miR-93 could directly target Orai1. SiRNA targeting Orai1 was sufficient to suppress TGF-β1-induced EMT and fibrogenesis in HK2 cells. Furthermore, Overexpression of ...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Curcumin and its demethoxy derivatives possess p300 HAT inhibitory activity and suppress hypertrophic responses in cardiomyocytes
Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Yoichi Sunagawa, Masafumi Funamoto, Shogo Sono, Kana Shimizu, Satoshi Shimizu, Mai Genpei, Yusuke Miyazaki, Yasufumi Katanasaka, Eriko Morimoto, Morio Ueno, Maki Komiyama, Hideaki Kakeya, Hiromichi Wada, Koji Hasegawa, Tatsuya MorimotoAbstractThe natural compound, curcumin (CUR), possesses several pharmacological properties, including p300-specific histone acetyltransferase (HAT) inhibitory activity. In our previous study, we demonstrated that CUR could prevent the development of cardiac hypertrophy by inhibiting p300-HAT...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Atractylodin attenuates lipopolysaccharide-induced acute lung injury by inhibiting NLRP3 inflammasome and TLR4 pathways
Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Fayin Tang, Kefeng Fan, Kunli Wang, Chuanzhou BianAbstractAcute lung injury (ALI) arises from uncontrolled pulmonary inflammation with high mortality rates. Atractylodin (Atr) is a polyethylene alkynes and has been reported to possess anti-inflammation effect. Thus, we aimed to investigate the protective effect of Atr on lipopolysaccharide (LPS)-induced inflammatory responses ALI. The results indicated that Atr treatment not only significantly attenuated LPS-stimulated histopathological changes but also lessened the myelo...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

The uricosuric effects of dihydropyridine calcium channel blockers in vivo using urate under-excretion animal models
Publication date: April 2018Source: Journal of Pharmacological Sciences, Volume 136, Issue 4Author(s): Takayuki Hori, Motoshi Ouchi, Naoyuki Otani, Masakatsu Nohara, Asuka Morita, Yusuke Otsuka, Promsuk Jutabha, Ikuko Shibasaki, Yasushi Matsushita, Tomoe Fujita, Hirotsugu Fukuda, Naohiko AnzaiAbstractThe purpose of this study was to create novel urate under-excretion animal models using pyrazinamide and to evaluate whether dihydropyridine calcium channel blockers (CCBs) have uricosuric effects in vivo.Adult male ICR mice were treated with pyrazinamide, vehicle (dimethyl sulfoxide: DMSO), or tap water. Thirty minu...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Establishment of an abnormal vascular patterning model in the mouse retina
In this study, we examined morphological and functional changes in retinal blood vessels and neurons in mice that had undergone short-term interruption of retinal vascular development through inhibition of vascular endothelial growth factor (VEGF) signaling. In mice treated with the VEGF receptor tyrosine kinase inhibitor KRN633 on postnatal day (P) 0 and 1, the vascular density in the retinal surface increased by P12, but development of deep retinal vascular plexus and choroidal vasculature was delayed until P14. Overall retinal morphology was mostly normal in KRN633-treated mice during the observation period (∼P28), ...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Neurotropin inhibits neuroinflammation via suppressing NF-κB and MAPKs signaling pathways in lipopolysaccharide-stimulated BV2 cells
In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively. Western blotting was conducted to measure the protein levels of major genes in MAPKs and NF-κB signaling pathways. Results demonstrated that NTP could attenuate the production of pro-inflammatory cytokines. Furthermore, NTP inhibited the act...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Therapeutic effects of the allosteric protein tyrosine phosphatase 1B inhibitor KY-226 on experimental diabetes and obesity via enhancements in insulin and leptin signaling in mice
In conclusion, KY-226 exerted anti-diabetic and anti-obesity effects by enhancing insulin and leptin signaling, respectively. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Polysulfide protects midbrain dopaminergic neurons from MPP+-induced degeneration via enhancement of glutathione biosynthesis
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Shuhei Takahashi, Akinori Hisatsune, Yuki Kurauchi, Takahiro Seki, Hiroshi KatsukiAbstractPolysulfides are endogenous sulfur-containing molecular species that may regulate various cellular functions. Here we examined the effect of polysulfides exogenously applied to rat midbrain slice cultures, to address their potential neuroprotective actions. Na2S3 at concentrations of 10 μM or higher prevented 1-methyl-4-phenylpyridinium (MPP+)-induced loss of dopaminergic neurons. Na2S4 at 10 μM also protected dopaminer...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Medaka as a model for ECG analysis and the effect of verapamil
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Manabu Yonekura, Nami Kondoh, Chong Han, Yuichi Toyama, Takayoshi Ohba, Kyoichi Ono, Shirou Itagaki, Hirofumi Tomita, Manabu MurakamiAbstractThe heart of the medaka, a small fish native to East Asia, has electrophysiological aspects similar to mammalian hearts. We found that the heart rates of medaka were more similar to humans than mice or rats. Medaka exhibited similar electrocardiogram patterns to those of humans, suggesting a similarity in cardiac impulse formation and propagation. Their hearts also exhibited similar re...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Blockade of voltage-dependent K+ current in rabbit coronary arterial smooth muscle cells by the tricyclic antidepressant clomipramine
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Hongliang Li, Sung Eun Shin, Jin Ryeol An, Mi Seon Seo, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L. Firth, Dae-Sung Lee, Mi-Jin Yim, Jeong Min Lee, Grace Choi, Il-Whan Choi, Won Sun ParkAbstractWe investigated the effect of the tricyclic antidepressant clomipramine on voltage-dependent K+ (Kv) channels in native rabbit coronary arterial smooth muscle cells. Our results showed that clomipramine inhibited vascular Kv channels in a concentration-dependent manner, with an IC50 value of 8.61 ± 4.86 μ...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Neuropeptide oxytocin enhances μ opioid receptor signaling as a positive allosteric modulator
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Yoshiyuki Meguro, Kanako Miyano, Shigeto Hirayama, Yuki Yoshida, Naoto Ishibashi, Takumi Ogino, Yuriko Fujii, Sei Manabe, Moeko Eto, Miki Nonaka, Hideaki Fujii, Yoichi Ueta, Minoru Narita, Naohiro Sata, Toshihiko Yada, Yasuhito UezonoAbstractOxytocin (OT) is a 9-amine neuropeptide that plays an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. OT has been reported to exert an analgesic effect in both humans and animals, and the results of certain animal experiments have shown that the a...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Oleanolic acid exerts bone protective effects in ovariectomized mice by inhibiting osteoclastogenesis
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Dongfeng Zhao, Xiaofeng Li, Yongjian Zhao, Ping Qiao, Dezhi Tang, Yan Chen, Chunchun Xue, Chenguang Li, Shufen Liu, Jing Wang, Sheng Lu, Qi Shi, Yan Zhang, Yufeng Dong, Yongjun Wang, Bing Shu, Xu FengAbstractPostmenopausal osteoporosis (POP) is quite prevalent and many new drugs are under development to obtain better therapeutic outcomes. Oleanolic acid (OA) has been reported to prevent bone loss in ovariectomized (OVX) rats by stimulating osteoblastogenesis. One previous study has demonstrated that acetate of OA suppressed...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Mechanisms underlying the relaxation by A484954, a eukaryotic elongation factor 2 kinase inhibitor, in rat isolated mesenteric artery
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Tomoko Kodama, Muneyoshi Okada, Hideyuki YamawakiAbstractEukaryotic elongation factor 2 kinase (eEF2K) is a calmodulin-related protein kinase which regulates protein translation. A484954 is an inhibitor of eEF2K. In the present study, we investigated the acute effects of A484954 on contractility of isolated blood vessels. Isometric contraction of rat isolated aorta and main branch of superior mesenteric artery (MA) was measured. Expression of an inward rectifier K+ (Kir) channel subtype mRNA and protein was examined. A48495...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

The neurosteroid allopregnanolone sulfate inhibits Nav1.3 α subunit-containing voltage-gated sodium channels, expressed in Xenopus oocytes
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Takafumi Horishita, Nobuyuki Yanagihara, Susumu Ueno, Dan Okura, Reiko Horishita, Tomoko Minami, Yuichi Ogata, Yuka Sudo, Yasuhito Uezono, Takashi KawasakiAbstractThe neurosteroid allopregnanolone has potent analgesic effects, and its potential use for neuropathic pain is supported by recent reports. However, the analgesic mechanisms are obscure. The voltage-gated sodium channels (Nav) α subunit Nav1.3 is thought to play an essential role in neuropathic pain. Here, we report the effects of allopregnanolone sulfate (AP...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Astrocytic Ca2+ responses in the spinal dorsal horn by noxious stimuli to the skin
In this study, we investigated whether SDH astrocytes respond to noxious and innocuous stimuli to the skin of normal mice using in vivo two-photon Ca2+ imaging under anesthesia. We found that noxious stimulation evoked by intraplantar formalin injection provoked an elevation in intracellular Ca2+ levels in SDH astrocytes. By contrast, neither instantaneous noxious pinching nor innocuous stimuli (cooling or brushing) to the hindpaw elicited astrocytic Ca2+ responses. Thus, SDH astrocytes could respond preferentially to a strong and/or sustained noxious stimulus. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Developmental trajectories of brain maturation and behavior: Relevance to major mental illnesses
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Sedona Lockhart, Akira Sawa, Minae NiwaAbstractAdverse events in childhood and adolescence, such as social neglect or drug abuse, are known to lead to behavioral changes in young adulthood. This is particularly true for the subset of people who are intrinsically more vulnerable to stressful conditions. Yet the underlying mechanisms for such developmental trajectory from early life insult to aberrant adult behavior remains elusive. Adolescence is a period of dynamic physiological, psychological, and behavioral changes, encom...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Berberine inhibits growth and inflammatory invasive phenotypes of ectopic stromal cells: Imply the possible treatment of adenomyosis
This study was to evaluate the potential therapeutic effect of BBR on ectopic endometrial stromal cells (EESCs) isolated from patients with adenomyosis. Our data showed that BBR significantly inhibited the proliferation and viability of eutopic endometrial stromal cells (EuESCs) and EESCs, while slightly affected the growth of normal endometrial stromal cells (NESCs). BBR markedly exhibited a growth inhibitory effect on EESCs by triggering apoptosis and cell cycle arrest, and alleviating the expression of inflammatory invasive phenotypes (IL-6, IL-8, TGF-β, EGF, VEGF, and MMP2). The alleviation of inflammatory invasiv...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Selectivity of Ca2+ channel blockers for dilator actions on the isolated lower esophageal sphincter and aorta from rats
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Akira Takahara, Shuhei Nozaki, Akane Ishiguro, Kaori Okamura, Xin Cao, Megumi Aimoto, Yoshinobu NagasawaAbstractWe compared dilator actions of representative four Ca2+ channel blockers on the isolated lower esophagus sphincter (LES) and thoracic aorta from rats. Verapamil, diltiazem, nifedipine and cilnidipine suppressed KCl-induced contractions of LES and thoracic aorta in a concentration-dependent manner. The order of selectivity for LES, which was calculated as ratio of IC50 value for thoracic aorta divided by that for L...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Dauricine combined with clindamycin inhibits severe pneumonia co-infected by influenza virus H5N1 and Streptococcus pneumoniae in vitro and in vivo through NF-κB signaling pathway
Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Hui Li, Xin Chen, Shu-Jun ZhouAbstractDauricine, isolated from Menispermum dauricum, has been widely used for treatment of various diseases, including cardiac ischemia and inflammation-related diseases. However, little is known regarding to the effect of dauricine on severe pneumonia. Therefore, the aim was to investigate the effect of dauricine on severe pneumonia and its mechanism during progress. Herein, H5N1 and Streptococcus pneumoniae (D39) were conducted to induce severe pneumonia in both BEAS-2B cells and mice. In&n...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Propofol induced diverse and subtype-specific translocation of PKC families
In this study, we performed real-time observation of propofol-induced PKC translocation in SH-SY5Y cells expressing PKCs fused with a fluorescent protein. Propofol unidirectionally translocated γPKC-GFP, a conventional PKC, and ζPKC-GFP, an atypical PKC, to the plasma membrane and nucleus, respectively, whereas the propofol-induced translocation of novel PKCs was diverse and subtype-specific among δPKC, εPKC and ηPKC. The propofol-induced translocation of εPKC-GFP was especially complicated and diverse, that is, 200 μM propofol first translocated εPKC-GFP to the perinucl...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Hypothermic preconditioning but not ketamine reduces oxygen and glucose deprivation induced neuronal injury correlated with downregulation of COX-2 expression in mouse hippocampal slices
This study was aimed to explore the effect of hypothermic and ketamine preconditioning on oxygen and glucose deprivation (OGD) induced neuronal injury in mouse hippocampal slices, and to investigate its possible mechanism. The population spike (PS) was recorded in the CA1 region of mouse hippocampal slices using extracellular recordings, Na+/K+ ATPase activity in slices was determined by spectrophotometer and the expression of Cyclooxygenase-2 (COX-2) was measured by Western blot. Ten min of OGD induced a poor recovery of PS in slices after reoxygenation. Hypothermic (33 °C) preconditioning delayed the appearance ...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Inhibition effect of glycyrrhiza polysaccharide (GCP) on tumor growth through regulation of the gut microbiota composition
In this study, we explore the anti-tumor mechanism of GCP from the angle of gut microbiota. Colon carcinoma cells (CT-26) were used to set up a tumor-bearing mouse model. After 14 days of GCP treatment, the weights of tumors were significantly reduced. In addition, HE staining of tissue sections reflected that GCP could effectively inhibit tumor metastasis. 16SrRNA high-throughput sequencing of fecal samples showed a significant change between the model group and GCP group in the composition of gut microbiota. Subsequently, gut microbiota depletion and fecal transplantation experiments further confirmed the relationship be...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Histamine elicits glutamate release from cultured astrocytes
Publication date: Available online 16 May 2018Source: Journal of Pharmacological SciencesAuthor(s): Anikó Kárpáti, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Takuro Matsuzawa, Haruna Kitano, Ryuichi Harada, Kazuhiko YanaiAbstractAstrocytes play key roles in regulating brain homeostasis and neuronal activity. This is, in part, accomplished by the ability of neurotransmitters in the synaptic cleft to bind astrocyte membrane receptors, activating signalling cascades that regulate concentration of intracellular Ca2+ ([Ca2+]i) and gliotransmitter release, including ATP and glutamate. Gliotransmitters...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

A study on indices of apixaban anticoagulation: A single-center prospective study
Publication date: Available online 16 May 2018Source: Journal of Pharmacological SciencesAuthor(s): Maki Komiyama, Yusuke Miyazaki, Hiromichi Wada, Moritake Iguchi, Mitsuru Abe, Hisashi Ogawa, Masaharu Akao, Hajime Yamakage, Noriko Satoh-Asahara, Yoichi Sunagawa, Tatsuya Morimoto, Koji HasegawaAbstractBackgroundDepending on the characteristics of patients, the blood concentration of apixaban can unexpectedly increase, possibly leading to bleeding events. Anti-FXa activity reflects the apixaban blood concentration; however, measurement of this activity is both time-consuming and expensive. The current study aimed to evaluat...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Enhancement of ghrelin-signaling system by Rikkunshi-To attenuates teriparatide-induced pica in rats
Publication date: Available online 17 May 2018Source: Journal of Pharmacological SciencesAuthor(s): Kouichi Yamamoto, Yukihiro Isogai, Takayuki Ishida, Keisuke HagiharaAbstractTeriparatide is clinically used for the treatment of osteoporosis; however, nausea is often observed in patients. Its insufficient control affects the ability to continue teriparatide therapy. Rikkunshi-To (RKT), a traditional Japanese herbal medicine, improves the gastrointestinal function via activation of the ghrelin-signaling system. We investigated the therapeutic effects of RKT on teriparatide-induced nausea in rats and the involvement of ghrel...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Neuregulin 1 regulates amyloid precursor protein cell surface expression and non-amyloidogenic processing
Publication date: Available online 29 May 2018Source: Journal of Pharmacological SciencesAuthor(s): Young-Jung Kim, Ji-Young Yoo, Ok-Soon Kim, Han-byeol Kim, Junghwa Ryu, Hye-Sun Kim, Jun-Ho Lee, Hong-Il Yoo, Dae-Yong Song, Tai-Kyoung Baik, Ran-Sook WooAbstractThe amyloid precursor protein (APP) is a key molecule in Alzheimer's disease. The prevailing view is that APP is initially transported to the plasma membrane as a full-length protein. Its localization at the cell surface can trigger downstream signaling and APP cleavage. Our previous work has shown that Neuregulin 1 (NRG1) has neuroprotective effects in an Alzheimer'...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Neurotropin inhibits neuronal activity through potentiation of sustained Kv currents in primary cultured DRG neurons
This study examined the effects of NTP on the activity of small dorsal root ganglion (DRG) neurons using whole-cell patch clamp recordings. After 3 days of treatment, NTP decreased current injection-induced firing activity of cultured DRG neurons by raising the current threshold for action potential generation. Additionally, NTP increased the sustained component of voltage-gated potassium (Kv) channel currents without affecting other K+ currents. These results suggest that NTP inhibits the firing activity of DRG neurons through augmentation of sustained Kv current. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Scoparone attenuates angiotensin II-induced extracellular matrix remodeling in cardiac fibroblasts
Publication date: Available online 2 June 2018Source: Journal of Pharmacological SciencesAuthor(s): Bao Fu, Yi Su, Xin Ma, Chunyan Mu, Fusheng YuAbstractScoparone is a biologically active constituent isolated from Artemisia capillaris and possesses a variety of pharmacological activities, such as anti-inflammatory, anti-tumor, anti-allergic and anti-cardiovascular activities. However, there are no studies focusing on the effects of scoparone against cardiac fibrosis. Therefore, the aim of this study was to investigate the effects of scoparone on Angiotensin II (Ang II)-induced extracellular matrix (ECM) remodeling and its ...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Mangiferin alleviates hypertension induced by hyperuricemia via increasing nitric oxide releases
In this study, we aimed to evaluate the effect of mangiferin on alleviating hypertension induced by hyperuricemia. Mangiferin (30, 60, 120 mg/kg) was administered intragastrically to hyperuricemic rats induced by gavage with potassium oxonate (750 mg/kg). Systolic blood pressure (SBP), serum levels of UA, nitric oxide (NO), C-reactionprotein (CRP) and ONOO− were measured. The mRNA and protein levels of endothelial nitric oxide synthase (eNOS), intercellular adhesion molecule-1 (ICAM-1), CRP were also analyzed. Human umbilical vein endothelial cells (HUVECs) were used in vitro studies. Administration of...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacological characterization of nicotine-induced tremor: Responses to anti-tremor and anti-epileptic agents
Publication date: Available online 7 June 2018Source: Journal of Pharmacological SciencesAuthor(s): Naofumi Kunisawa, Saki Shimizu, Masaki Kato, Higor A. Iha, Chihiro Iwai, Mai Hashimura, Mizuki Ogawa, Shohei Kawaji, Kazuma Kawakita, Keisuke Abe, Yukihiro OhnoAbstractWe previously showed that nicotine evoked kinetic tremor by activating the inferior olive, which is implicated in the pathogenesis of essential tremor, via α7 nicotinic acetylcholine receptors. Here, we evaluated the effects of various anti-tremor and anti-epileptic agents on nicotine-induced tremor in mice to clarify the pharmacological characteristics ...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

LncRNA TUG1 promoted viability and associated with gemcitabine resistant in pancreatic ductal adenocarcinoma
ConclusionTUG1 promoted the viability of PDAC cells and enhanced its resistance of gemcitabine. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Role of the cannabinoid signaling in the brain orexin- and ghrelin-induced visceral antinociception in conscious rats
Publication date: Available online 7 June 2018Source: Journal of Pharmacological SciencesAuthor(s): Toshikatsu Okumura, Tsukasa Nozu, Shima Kumei, Masumi OhhiraAbstractWe hypothesized that the cannabinoid (CB) system may mediate the brain orexin- or ghrelin-induced visceral antinociception. Intraperitoneal injection of either CB1/2 agonist, WIN 55212 or O-Arachidonoyl ethanolamine increased the threshold volume of colonic distension-induced abdominal withdrawal reflex in rats, suggesting CB could induce visceral antinociception. Pretreatment with either the CB1 or CB2 antagonist potently blocked the centrally injected orex...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

γ-oryzanol ameliorates the acute stress induced by behavioral anxiety testing in mice
In conclusion, GORZ has potential ant-anxiety effect in the treatment of weak behavioral test-induced stress. (Source: Journal of Pharmacological Sciences)
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Involvement of GABAB receptor in the antihypersensitive effect in anterior cingulate cortex of partial sciatic nerve ligation model
Publication date: Available online 7 June 2018Source: Journal of Pharmacological SciencesAuthor(s): Keisuke Migita, Yu Matsuzaki, Kohei Koga, Taichi Matsumoto, Kenichi Mishima, Shuji Hara, Kenji HondaAbstractThe role of the GABAB receptor in the anterior cingulate cortex (ACC) of neuropathic pain is unclear. Injection of a GABAB receptor antagonist CGP35348 into the ACC induced mechanical hypersensitivity in normal rats. Activation of the GABAB receptor injected by a GABAB receptor agonist baclofen into the ACC attenuated mechanical hypersensitivity in partial sciatic nerve ligation (PSNL) rats. Co-microinjection of CGP353...
Source: Journal of Pharmacological Sciences - July 10, 2018 Category: Drugs & Pharmacology Source Type: research