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Journal of Pharmacological Sciences

Salamet Edirs, Lan Jiang, XueLei Xin, Haji Akber Aisa
Kursi Wufarikun Ziyabit (KWZ) is a traditional prescription that used in folk tea drinking for its health care effect in treatment of type 2 diabetes mellitus (T2DM) in central Asia. However, the underlying mechanism of KWZ in T2DM has not been investigated extensively. This study designed to observe the effect of KWZ on glucose consumption and assess the molecular mechanism on associated proteins in insulin signaling and ER stress pathway in L6 rat skeletal muscle cells. The results showed that, KWZ exhibited proteins of PTP-1B and α-glycosidase inhibitory activity in vitro...
June 21, 2018: Journal of Pharmacological Sciences
Yoshifumi Hida, Shinsuke Nakamura, Anri Nishinaka, Yuki Inoue, Masamitsu Shimazawa, Hideaki Hara
Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors are used to treat glaucoma patients and have protective effects on ischemic states. However, it is poorly understood how the ROCK pathway affects the pathological signs of retinal vein occlusion (RVO). In this study, we evaluated the effects of ripasudil, a ROCK inhibitor, on a murine RVO model. In vivo, RVO was induced by retinal vein laser irradiation in mice, and evaluated with ripasudil. In vitro, the effects of ripasudil were examined on tight junction protein integrity in human retinal microvascular endothelial cells (HRMECs)...
June 19, 2018: Journal of Pharmacological Sciences
Ai Goto, Hiroko Izumi-Nakaseko, Mihoko Hagiwara-Nagasawa, Koki Chiba, Kentaro Ando, Atsuhiko T Naito, Atsushi Sugiyama
We analyzed torsadogenic and pharmacokinetic profile of E-4031 using chronic atrioventricular block dogs. E-4031 in intravenous doses of 0.03, 0.1 and 0.3 mg/kg over 10 min prolonged QT/QTc, and increased short-term variability of QT in a dose-related manner (n = 4), resulting in onset of torsade de pointes in 1 animal after the middle dose and 4 animals after the high dose, while it attained peak plasma concentrations of 16.5, 60.5 and 182.5 ng/mL at 10 min after their start of administration, respectively (n = 2)...
June 18, 2018: Journal of Pharmacological Sciences
Namkwon Kim, Jimin Do, Jae-Sung Bae, Hee Kyung Jin, Jong-Ho Kim, Kyung-Soo Inn, Myung Sook Oh, Jong Kil Lee
Inflammatory processes in the central nervous system are feature among biological reactions to harmful stimuli such as pathogens and damaged cells. In resting conditions, microglia are involved in immune surveillance and brain homeostasis. However, the activation of abnormal microglia can be detrimental to neurons, even resulting in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Therefore, normalization of microglial activation is considered a promising strategy for developing drugs that can treat or prevent inflammation-related brain diseases...
June 18, 2018: Journal of Pharmacological Sciences
Yan Sun, Liru Xun, Gang Jin, Lei Shi
Oxidative stress, inflammation and cell apoptosis are important mechanisms of renal ischemia/reperfusion (I/R) injury. Salidroside, a natural phenylpropanoid glycoside, possesses anti-inflammatory, anti-oxidative, and anti-apoptotic effects. However, the effect of salidroside on renal I/R injury has not been fully elucidated. The present study aimed to investigate the effect of salidroside on renal I/R injury in vitro. Our results showed that salidroside improved the viability of human renal tubular epithelial cells (HK-2) in response to hypoxia/reoxygenation (H/R)...
June 18, 2018: Journal of Pharmacological Sciences
Fan Yang, Xiaofang Li, Lingjuan Zhang, Lina Cheng, Xiuling Li
OBJECTIVE: To investigate the underlying mechanism of lncRNA TUG1 in pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of TUG1 was defined by qRT-PCR. The apoptotic cells were detected by flow cytometry assay. The cell migration and invasion were measured by scratch assay and Transwell assay. The level of ERK pathway was detected using Western blot. RESULTS: Compared with normal tissues and cells, the expression of TUG1 was up-regulated in pancreatic cancer tissue and cells...
June 7, 2018: Journal of Pharmacological Sciences
Toshikatsu Okumura, Tsukasa Nozu, Shima Kumei, Masumi Ohhira
We 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 orexin-A-induced antinociceptive action against colonic distension while CB2 but not CB1 antagonist blocked the brain ghrelin-induced visceral antinociception...
June 7, 2018: Journal of Pharmacological Sciences
Naofumi Kunisawa, Saki Shimizu, Masaki Kato, Higor A Iha, Chihiro Iwai, Mai Hashimura, Mizuki Ogawa, Shohei Kawaji, Kazuma Kawakita, Keisuke Abe, Yukihiro Ohno
We 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 of nicotine tremor. Drugs effective for essential tremor, propranolol, diazepam and phenobarbital, all significantly inhibited kinetic tremor induced by an intraperitoneal (i...
June 7, 2018: Journal of Pharmacological Sciences
Hua Yang, Wenwei Bai, Lihui Gao, Jun Jiang, Yingxi Tang, Yanfen Niu, Hua Lin, Ling Li
Mangiferin, a natural glucosyl xanthone, was confirmed to be an effective uric acid (UA)- lowering agent with dual action of inhibiting production and promoting excretion of UA. 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...
June 6, 2018: Journal of Pharmacological Sciences
Bao Fu, Yi Su, Xin Ma, Chunyan Mu, Fusheng Yu
Scoparone 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 possible mechanism in cardiac fibroblasts (CFs)...
June 2, 2018: Journal of Pharmacological Sciences
Hiroyuki Kawai, Nozomi Asaoka, Takahito Miyake, Kazuki Nagayasu, Takayuki Nakagawa, Hisashi Shirakawa, Shuji Kaneko
Neurotropin (NTP) is a Japanese analgesic agent for treating neuropathic pain; however, its method of action remains unclear. 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...
May 31, 2018: Journal of Pharmacological Sciences
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 Woo
The 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's disease model. In the present study, we examine whether NRG1 signaling is involved in APP expression and non-amyloidogenic processing in neuronal cells...
May 29, 2018: Journal of Pharmacological Sciences
Kouichi Yamamoto, Yukihiro Isogai, Takayuki Ishida, Keisuke Hagihara
Teriparatide 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 ghrelin in these effects. We previously reported that ovariectomized rats showed pica (kaolin ingestion), a behavior that can be used to assess nausea in rats, after the subcutaneous administration of teriparatide; thus, the behavior was used as an index of nausea...
May 17, 2018: Journal of Pharmacological Sciences
Maki Komiyama, Yusuke Miyazaki, Hiromichi Wada, Moritake Iguchi, Mitsuru Abe, Hisashi Ogawa, Masaharu Akao, Hajime Yamakage, Noriko Satoh-Asahara, Yoichi Sunagawa, Tatsuya Morimoto, Koji Hasegawa
BACKGROUND: Depending 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 evaluate the usefulness of routinely measured coagulation indices as future indicators of the efficacy and safety of apixaban. METHODS: Eighteen nonvalvular atrial fibrillation patients administered apixaban (average, 52...
May 16, 2018: Journal of Pharmacological Sciences
Anikó Kárpáti, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Takuro Matsuzawa, Haruna Kitano, Ryuichi Harada, Kazuhiko Yanai
Astrocytes 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 contribute to dendrite formation and synaptic plasticity, and in some cases, exacerbate neurodegeneration. The neurotransmitter histamine participates in several physiological processes, such as the sleep-wake cycle and learning and memory...
May 16, 2018: Journal of Pharmacological Sciences
Tomoko Kodama, Muneyoshi Okada, Hideyuki Yamawaki
Eukaryotic 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. A484954 caused relaxation in endothelium-intact [E (+)] and -denuded [E (-)] aorta or MA precontracted with noradrenaline (NA)...
May 2018: Journal of Pharmacological Sciences
Takafumi Horishita, Nobuyuki Yanagihara, Susumu Ueno, Dan Okura, Reiko Horishita, Tomoko Minami, Yuichi Ogata, Yuka Sudo, Yasuhito Uezono, Takashi Kawasaki
The 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 Nav 1.3 is thought to play an essential role in neuropathic pain. Here, we report the effects of allopregnanolone sulfate (APAS) on sodium currents (INa ) in Xenopus oocytes expressing Nav 1.3 with β1 or β3 subunits. APAS suppressed INa of Nav 1.3 with β1 and β3 in a concentration-dependent manner (IC50 values; 75 and 26 μmol/L)...
May 2018: Journal of Pharmacological Sciences
Sedona Lockhart, Akira Sawa, Minae Niwa
Adverse 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, encompassing a distinct neurodevelopmental stage called the 'critical period'...
May 2018: Journal of Pharmacological Sciences
Kohei Yoshihara, Tsuyoshi Matsuda, Yuta Kohro, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Makoto Tsuda
The role of astrocytes in the spinal dorsal horn (SDH) for sensory information processing under normal conditions is poorly understood. 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...
May 2018: Journal of Pharmacological Sciences
Hui Li, Xin Chen, Shu-Jun Zhou
Dauricine, 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 vitro, dauricine reversed the protein and mRNA expressions of TNF-α, IL-6 and IL-1β, examined by ELISA and qRT-PCR assay, respectively...
May 2018: Journal of Pharmacological Sciences
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