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Journal of Pharmacological Sciences

Shinya Takigawa, Brian Frondorf, Shengzhi Liu, Yang Liu, Baiyan Li, Akihiro Sudo, Joseph M Wallace, Hiroki Yokota, Kazunori Hamamura
Salubrinal is an agent that reduces the stress to the endoplasmic reticulum by inhibiting de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). We and others have previously shown that the elevated phosphorylation of eIF2α stimulates bone formation and attenuates bone resorption. In this study, we applied salubrinal to a mouse model of osteogenesis imperfecta (Oim), and examined whether it would improve Oim's mechanical property. We conducted in vitro experiments using RAW264.7 pre-osteoclasts and bone marrow derived cells (BMDCs), and performed in vivo administration of salubrinal to Oim (+/-) mice...
October 1, 2016: Journal of Pharmacological Sciences
Ryota Araki, Yosuke Hiraki, Shoji Nishida, Yuka Inatomi, Takeshi Yabe
Emotional impairments such as depressive symptoms often develop in patients with sustained and systemic immune activation. The objective of this study is to investigate the effect of gomisin N, a dibenzocyclooctadiene lignan isolated from the dried fruits of Schisandra chinensis (Turcz.) Baill., which exhibited inhibitory effects of the bacterial endotoxin lipopolysaccharide (LPS)-induced NO production in a screening assay, on inflammation-induced depressive symptoms. We examined the effects of gomisin N on inflammation induced by LPS in murine microglial BV-2 cells and on LPS-induced behavioral changes in mice...
September 28, 2016: Journal of Pharmacological Sciences
Wen Cao, Chao Hu, Lingling Wu, Liba Xu, Weizhe Jiang
The aim of this study was to explore the anti-tumor effect and therapeutic potential of rosmarinic acid (RA) in the treatment of hepatocellular carcinoma (HCC). RA at 75, 150 and 300 mg/kg was given to H22 tumor-bearing mice by intragastric administration once daily for 10 consecutive days. Levels of inflammatory and angiogenic factors, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and transforming growth factor-β (TGF-β) were measured by enzyme linked immunosorbent assays (ELISA)...
September 14, 2016: Journal of Pharmacological Sciences
Ryoko Tsukahara, Hiroshi Ueda
Lysophosphatidic acid (LPA) initiates demyelination following peripheral nerve injury, which causes neuropathic pain. Our previous in vivo and ex vivo studies using mice have demonstrated that LPA-induced demyelination of spinal dorsal roots is attributed by the LPA1-type receptor-mediated down-regulation of myelin-related molecules, such as MBP and MPZ. In this study using S16 mature-type Schwann cells, we found that LPA-induced down-regulation of myelin-related genes is attributed by the activation of LPA1 receptor, Rho kinase, and p300, leading to an acetylation of NFκB, which down-regulates the transcription of Sox10, MBP and MPZ genes...
September 12, 2016: Journal of Pharmacological Sciences
Keitaro Hayashi, Promsuk Jutabha, Sumiko Maeda, Yothaisong Supak, Motoshi Ouchi, Hitoshi Endou, Tomoe Fujita, Masayuki Chida, Naohiko Anzai
L-type amino acid transporter 1 (LAT1, SLC7A5) incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma...
July 27, 2016: Journal of Pharmacological Sciences
Sha Liu, Shuang-Qi Tang, Heng-Jing Cui, Sha Yin, Ming Yin, Hong Zhao, Ling-Hua Meng, Ze-Jian Wang, Yang Lu
Recently, anandamide (AEA) analogues have been well recognized for its potent neuroprotective effects in counteracting the deterioration of Alzheimer's disease (AD) brains through multiple pathological processes. In our previous studies, dipotassium N-stearoyltyrosinate (NSTK), an AEA analogue synthesized by our laboratory was reported to exert significant efficacy through multiple interventions. Within this study, the amyloid precursor protein (APP)SWE/presenilin-1 (PS1)M146V/TauP301L mouse (3×Tg-AD) model was used to explore further the neuroprotective effects of NSTK and its underlying mechanisms...
September 2016: Journal of Pharmacological Sciences
Masaki Yamamoto, Takahiro Shimizu, Shogo Shimizu, Youichirou Higashi, Kumiko Nakamura, Mikiya Fujieda, Motoaki Saito
Naftopidil, an α1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP) plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA). NA (3 or 30 μg/kg) was administered into the left ventricle (i.c.v.) of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i...
September 2016: Journal of Pharmacological Sciences
Junichi Ikeda, Naoya Kimoto, Tetsuya Kitayama, Shunji Kunori
Saxagliptin, a potent and selective DPP-4 inhibitor, is characterized by its slow dissociation from DPP-4 and its long half-life and is expected to have a potent tissue membrane-bound DPP-4-inhibitory effect in various tissues. In the present study, we examined the effects of saxagliptin on in situ cardiac DPP-4 activity. We also examined the effects of saxagliptin on isoproterenol-induced the changes in the early stage such as, myocardial remodeling and cardiac diastolic dysfunction. Male SD rats treated with isoproterenol (1 mg/kg/day via osmotic pump) received vehicle or saxagliptin (17...
September 2016: Journal of Pharmacological Sciences
Sun Ae Kim, Kyung Young Lee, Jae-Ryong Kim, Hyoung Chul Choi
The prevalence rate of cardiovascular disease is higher for males than females, and estradiol (E2) induces AMP-activated protein kinase (AMPK) activation, which is known to regulate proliferation of VSMC. We identified the estrogenic properties of nordihydroguaiaretic acid (NDGA, a lignan phytoestrogen) that inhibit VSMC proliferation and explored the underlying mechanisms. Both the phosphorylation and expression of LKB1 were increased by NDGA. In addition, NDGA significantly attenuated angiotensin II (Ang II)-induced VSMC proliferation...
September 2016: Journal of Pharmacological Sciences
Nanxi Liu, Shogo Shimizu, Takahiro Shimizu, Kumiko Nakamura, Masaki Yamamoto, Youichirou Higashi, Motoaki Saito
We investigated the protective effects of a selective α1A-adrenoceptor antagonist, silodosin (Silod) on urinary bladder function in cyclophosphamide (CYP)-induced cystitis rats, with and without desensitization of the capsaicin (CAP)-sensitive afferent nerve pathway. Male Wistar rats (310-400 g) were pretreated with Silod (0, 100, or 300 μg/kg/day, p.o.) for 1 week before cystometry, and were administered either CYP (150 mg/kg, i.p.) or saline 2 days before the experiment. In another experiment, the rats were treated with CAP (125 mg/kg, s...
September 2016: Journal of Pharmacological Sciences
Suguru Ueda, Daiki Masukawa, Motokazu Koga, Yoshio Goshima
Through its conversion to dopamine by aromatic l-amino acid decarboxylase (AADC), l-3,4-dihydroxyphenylalanine (l-DOPA) replenishes depleted brain dopamine in Parkinson's disease patients. We recently identified GPR143 as a candidate receptor for l-DOPA. In this study, we investigated the behavioral actions of l-DOPA in wild type (wt) and Gpr143-deficient mice. l-DOPA dose-dependently (10-100 mg/kg, i.p.) induced ptosis under treatment with 3-hydroxybenzylhydrazine, a centrally acting AADC inhibitor. This effect was not mimicked by 3-O-methyldopa...
September 2016: Journal of Pharmacological Sciences
Mio Matsui, Kosuke Tanaka, Naoki Higashiguchi, Hisato Okawa, Yoichi Yamada, Ken Tanaka, Soichiro Taira, Tomoko Aoyama, Misaki Takanishi, Chika Natsume, Yuuki Takakura, Norihisa Fujita, Takeshi Hashimoto, Takashi Fujita
Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. In vitro analysis showed that UV irradiation of human dermal fibroblasts caused production of intracellular reactive oxygen species (ROS) without cellular toxicity...
September 2016: Journal of Pharmacological Sciences
Daisuke Nakano, Akira Nishiyama
The number of people being diagnosed with end-stage renal disease is increasing globally. Therapeutic options to slow or halt the progression of kidney disease are limited and are not always successful, despite the increasing body of research and number of basic scientific reports in this field. Further studies are required to investigate new approaches to renal pathophysiology. State of the art optical imaging is a powerful tool used to non-invasively observe the pathophysiology of small animals and has the potential to elucidate the unknown mechanisms of renal disease and aid in our understanding of the disease...
September 2016: Journal of Pharmacological Sciences
Shiori Maeda, Keita Sasaki, Sebok Kumar Halder, Wakako Fujita, Hiroshi Ueda
Prothymosin alpha (ProTα) suppresses stress-induced necrosis of cultured cortical neurons. As neuroprotection alone could not explain the long-lasting protective actions against cerebral ischemia by ProTα, we further examined whether ProTα, in addition to neuroprotective effects, has other anti-ischemic activities. When recombinant mouse ProTα (rmProTα) at 0.3 mg/kg was intravenously (i.v.) given 2 h after the start of tMCAO, all mice survived for more than 14 days. In evaluation of CD31- and tomato lectin-labeling as well as IgG and Evans blue leakage, rmProTα treatment (0...
September 2016: Journal of Pharmacological Sciences
Xiulu Ruan, Stanley Martin Hall, Alan David Kaye
No abstract text is available yet for this article.
September 2016: Journal of Pharmacological Sciences
Luca Bellini, Marta Vadori, Giulia Maria De Benedictis, Roberto Busetto
This study investigated the effect of morphine, fentanyl, butorphanol and buprenorphine on viability and caspase-3 activity in renal proximal tubular cells exposed to opioids for 2 h before or 12 h after chemical anoxia. Cell viability decreased regardless the treatment although intracellular ATP content was elevated in morphine and fentanyl pre-treated cells at 12 h. Anoxia increased caspase activity but this effect was significantly reduced in cells treated before or after with morphine, fentanyl and in cell treated with butorphanol for 12 h...
August 2016: Journal of Pharmacological Sciences
Toru Hosoi, Mai Kakimoto, Keigo Tanaka, Jun Nomura, Koichiro Ozawa
A pharmacological approach to ameliorate Alzheimer's disease (AD) has not yet been established. In the present study, we investigated the pharmacological characteristics of the recently identified memory-enhancing compound, ISRIB for the amelioration of AD. ISRIB potently attenuated amyloid β-induced neuronal cell death at concentrations of 12.5-25 nM, but did not inhibit amyloid β production in the HEK293T cell line expressing the amyloid precursor protein (APP). These results suggest that ISRIB possesses the unique pharmacological property of attenuating amyloid β-induced neuronal cell death without affecting amyloid β production...
August 2016: Journal of Pharmacological Sciences
Wataru Nemoto, Kotaro Yamada, Yoshiki Ogata, Osamu Nakagawasai, Katsuhito Onodera, Hidetomo Sakurai, Koichi Tan-No
We examined the effect of chondroitin sulfate (CS), a compound used in the treatment of osteoarthritis and joint pain, on the formalin-induced tactile allodynia in mice. A repeated oral administration of CS (300 mg/kg, b.i.d.) significantly ameliorated the formalin-induced tactile allodynia from day 10 after formalin injection. On day 14, the phosphorylation of spinal p38 MAPK and subsequent increase in c-Fos-immunoreactive dorsal lumbar neurons were attenuated by the repeated administration of CS. These findings suggest that CS attenuates formalin-induced tactile allodynia through the inhibition of p38 MAPK phosphorylation and subsequent up-regulation of c-Fos expression in the dorsal lumbar spinal cord...
August 2016: Journal of Pharmacological Sciences
Tsugunobu Andoh, Ayumi Sakamoto, Yasushi Kuraishi
Oxaliplatin causes peripheral neuropathy as a major dose-limiting side effect, and the control of this neuropathy is difficult. This study was designed to investigate whether prophylactic repetitive administration of 5-HT1A receptor agonists inhibits oxaliplatin-induced mechanical allodynia in mice. Repetitive administration of 5-HT1A receptor agonists (xaliproden and tandospirone) inhibited mechanical allodynia induced by a single intraperitoneal injection of oxaliplatin. These agonists also inhibited oxaliplatin-induced mast cell migration, which is involved in the induction of mechanical allodynia...
August 2016: Journal of Pharmacological Sciences
Eun-Yeong Kim, Hee-Jung Choi, Tae-Wook Chung, Jun-Yong Choi, Hyung Sik Kim, Yeon-Seop Jung, Syng-Ook Lee, Ki-Tae Ha
The leaves and stems of Perilla frutescens var. acuta Kudo (PF) have been used to prevent threatened abortion in traditional medicine in the East Asian countries. Because reduced receptivity of endometrium is a cause of abortion, we analyzed the action of PF on the endometrial receptivity. PF increased the level of leukemia inhibitory factor (LIF), a major cytokine regulating endometrial receptivity, and LIF receptor in human endometrial Ishikawa cells. The PF-induced LIF expression was mediated by c-jun N-terminal kinase (JNK) and p38 pathways...
August 2016: Journal of Pharmacological Sciences
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