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Journal of Pharmacological Sciences

Yongmei Zhao, Yuyou Huang, Yalan Fang, Haiping Zhao, Wenjuan Shi, Jincheng Li, Yunxia Duan, Yuwei Sun, Li Gao, Yumin Luo
Nitrosative/oxidative stress plays an important role in neuronal death following cerebral ischemia/reperfusion (I/R). Chrysophanol (CHR) has been shown to afford significant neuroprotection on ischemic stroke, however, whether its mechanism is related to attenuating nitrosative/oxidative stress is not clear. In the present study, we investigated the effect of CHR on neuronal injury related to nitric oxide (NO) production by using mouse middle cerebral artery occlusion (MCAO) model. Our results revealed that nitrite plus nitrate (NOx - ) and 3-nitrotyrosine (3-NT) levels increased in ischemic brain 14 days after reperfusion, and were subsequently attenuated by CHR treatment...
August 25, 2018: Journal of Pharmacological Sciences
Fabricio M Locatelli, Takashi Kawano, Hideki Iwata, Bun Aoyama, Satoru Eguchi, Atsushi Nishigaki, Daiki Yamanaka, Hiroki Tateiwa, Marie Shigematsu-Locatelli, Masataka Yokoyama
The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group)...
August 25, 2018: Journal of Pharmacological Sciences
Ziwei Wang, Junqing Zhang, Limei Wang, Wei Li, Lei Chen, Jingjing Li, Dan Zhao, Hong Zhang, Xiaohui Guo
Glycine exerts renoprotective effects, but the mechanism remains unclear. Glycine is increasingly recognized as a factor that attenuates oxidative stress, a key mechanism underlying diabetic nephropathy. In this study, we investigated the effects of glycine on diabetic renal injury and oxidative stress by adding 1% glycine in the drinking water of rats with streptozotocin-induced diabetes for 20 weeks. Glycine levels decreased in the plasma and kidney homogenates of diabetic rats but were restored by oral glycine administration...
August 25, 2018: Journal of Pharmacological Sciences
Zhiqi Xie, Yukio Ago, Naoki Okada, Masashi Tachibana
Immune checkpoint blockade (ICB) is a promising novel therapy for multiple cancer types; however, most patients show limited or no clinical response. Accumulating evidence indicates that myeloid-derived suppressor cells (MDSCs) are a major factor responsible for immunosuppression in patients with cancer. Therefore, identifying effective therapies that deplete or modulate MDSCs is essential. In this study, we focus on the anticonvulsant drug valproic acid (VPA), which has additional activities including anticancer and immunoregulation by inhibition of histone deacetylases...
August 24, 2018: Journal of Pharmacological Sciences
Hongfeng Zhang, Lei Liu, Ling Li
Lupus nephritis, one of the most serious complications of systemic lupus erythematosus (SLE), has been confirmed in a large number of clinical surveys. Current studies have suggested that inflammatory situation is generally considered to facilitate the occurrence and development of lupus nephritis. Previous research found that Fcγ receptor I (FcγRI) was compulsory for several autoimmune and inflammatory diseases, and it might be involved in the treatment of lupus nephritis. Furthermore, the possible molecular mechanism of the role of FcγRI in lupus nephritis still needs a further study...
August 18, 2018: Journal of Pharmacological Sciences
Keita Kitamura, Ryo Ito, Kenta Umehara, Hanae Morio, Kosuke Saito, Shota Suzuki, Mari Hashimoto, Yoshiro Saito, Naohiko Anzai, Hidetaka Akita, Kan Chiba, Tomomi Furihata
Astrocytes have shown longstanding promise as therapeutic targets for various central nervous system diseases. To facilitate drug development targeting astrocytes, we have recently developed a new conditionally immortalized human astrocyte cell line, termed HASTR/ci35 cells. In this study, in order to further increase their chances to contribute to various astrocyte studies, we report on the development of a culture method that improves HASTR/ci35 cell differentiation status and provide several proofs related to their astrocyte characteristics...
August 9, 2018: Journal of Pharmacological Sciences
Beverley J Davis, Christopher R Chapple, Donna J Sellers, Alisdair L Naylor, David Sillar, Alistair Campbell, Russ Chess-Williams
α1 -adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α1A -adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α1L -adrenoceptor. Functional experiments using subtype selective agonists and antagonists, along with radioligand ([3 H]tamsulosin) binding assays, were used to determine the α1 -adrenoceptor population. A61603, a α1A -adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline...
August 9, 2018: Journal of Pharmacological Sciences
Mari Endo, Masatoshi Hori, Hiroshi Ozaki, Tetsuro Oikawa, Hiroshi Odaguchi, Toshihiko Hanawa
Zingiberis processum rhizoma (ZPR) is a major active component of daikenchuto (DKT), which induces anti-inflammatory action by inhibiting macrophage infiltration. However, it is unclear whether ZPR is related to DKT-induced anti-inflammatory action via a reduction of neutrophil infiltration against postoperative ileus (POI). In this study, we orally administered individual herbal components of DKT to mice four times before and after intestinal manipulation (IM). The anti-inflammatory action of each crude drug was evaluated by histochemical analysis of relevant molecules...
August 6, 2018: Journal of Pharmacological Sciences
Yoshiki Kuse, Kei Takahashi, Yuki Inoue, Hiroshi Izawa, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara
Our previous studies found that an anti-placental growth factor (PlGF) antibody protected the retina in light-induced retinal damage model, a model of non-exudative age-related macular degeneration (AMD). Aflibercept is an inhibitor of vascular endothelial growth factor (VEGF) and PlGF. In present study, we revealed that the intravitreal injection of aflibercept lessens light-induced retinal damage, while anti-VEGF antibody has no effect on the light-exposed retina. Moreover, PlGF disrupted the tight junctions between the human retinal pigment epithelial cells in vitro, and aflibercept blocked the disruption...
August 4, 2018: Journal of Pharmacological Sciences
Hiroko Izumi-Nakaseko, Mihoko Hagiwara-Nagasawa, Atsuhiko T Naito, Ai Goto, Koki Chiba, Yuko Sekino, Yasunari Kanda, Atsushi Sugiyama
We examined electrophysiological indices of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) sheets in order to quantitatively estimate Na+ , K+ and Ca2+ channel blocking actions of bepridil and amiodarone using microelectrode array system in comparison with that of E-4031. We analyzed the field potential duration, effective refractory period, current threshold and conduction property using a programmed electrical stimulation protocol to obtain the post repolarization refractoriness and coefficient a of the relationship between the pacing cycle length and field potential duration...
August 4, 2018: Journal of Pharmacological Sciences
Jing Xu, Yasushi Yabuki, Mengze Yu, Kohji Fukunaga
T-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. Chronic SAK3 administration (0.5 or 1.0 mg/kg, p...
July 17, 2018: Journal of Pharmacological Sciences
Yunfei Zhang, Ping Huang, Xuewen Liu, Yuchen Xiang, Te Zhang, Yezi Wu, Jiaxin Xu, Zhiting Sun, Weiguo Zhen, Liang Zhang, Yuan Si, Ying Liu
The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular process that occurs during cancer progression and metastasis, has been reported to promote drug resistance in several previous studies. Consequently, ongoing research has been focused on exploring therapeutic options for preventing EMT to delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component extracted from Paris polyphylla that displays anti-cancer properties...
July 2018: Journal of Pharmacological Sciences
Qincai Tang, Haixia Ren, Lin Yan, Xiaojing Quan, Hong Xia, Hesheng Luo
Diallyl trisulfide (DATS) is an active organosulfide component of allicin and has several beneficial effects, including antimicrobial, antioxidant, cardioprotective and anticancer effects. Few studies have shown the modulatory effect of DATS on L-type calcium channels in rat colonic smooth muscle cells and colonic motility. To investigate the modulatory effect of DATS on L-type calcium channels in rat colonic smooth muscle and colonic contraction, L-type calcium channel currents were recorded, and colonic contractility in longitudinal and circular smooth muscle strips was measured...
July 2018: Journal of Pharmacological Sciences
Botao Wang, Xin Zheng, Jing Liu, Zhen Zhang, Chongyang Qiu, Lei Yang, Lanqiu Zhang, Qi Zhang, Hongwei Gao, Ximo Wang
Pancreatic cancer has remained a major cause of cancer-related deaths. A hallmark of pancreatic cancer is extensive stromal reactions, resulting in a unique tumor microenvironment, especially the involvement of macrophages. These tumor-educated cells limit the efficacy of chemotherapy. Therefore, it is necessary to identify an effective treatment strategy. In this study, we aimed to explore the anti-tumor and immunomodulatory effects of osthole on pancreatic cancer. We found that osthole suppressed Panc 02 cell migration and proliferation and induced apoptosis as shown in vitro...
July 2018: Journal of Pharmacological Sciences
Fang Jiang, De-Long Zhang, Min Jia, Wei-Hua Hao, Yong-Jun Li
Mangiferin (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 nitric oxide (NO) in mice were evaluated. The expression levels of PI3K, AKT, eNOS, PTEN and their phosphorylated proteins were measured by western blots...
July 2018: Journal of Pharmacological Sciences
Qin Chen, Haoran Zhang, Meng Wu, Qin Wang, Lusong Luo, Haikuo Ma, Xiaohu Zhang, Sudan He
Aberrant 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 apoptosis represents an attractive therapeutic strategy to eliminate tumor cells. To explore new Hh antagonists with apoptosis-inducing activity, we screened a set of ∼300 potential SMO antagonists with novel scaffold structures...
July 2018: Journal of Pharmacological Sciences
Kohei Takahashi, Osamu Nakagawasai, Wataru Nemoto, Takayo Odaira, Wakana Sakuma, Koichi Tan-No
Olfactory bulbectomized (OBX) mice exhibit depressive-like behaviors and memory deficits. We have reported that aripiprazole (ARI) ameliorates the behavioral hyper-responsivity to dopamine agonists and memory deficits in OBX mice; however, it is unclear whether ARI affects OBX-induced depressive-like behavior. To address this question, we evaluated the effect of ARI on depressive-like behavior in OBX mice using the forced swim test (FST). In addition, we investigated the effect of ARI on c-Fos expression in the prefrontal cortex (PFC), striatum, and hippocampus of OBX mice using western blotting...
July 2018: Journal of Pharmacological Sciences
Zhiyuan Fang, Li Ban, Yanan Li, Wenchang Yuan, Zhihua Liu, Ting Liu, Xiaomei Li, Kwok-Yin Wong, Yujing Lu, Ning Sun, Xingang Yao
The 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 the MIC values from 0.75 μg/mL to 6 μg/mL. In addition, this compound combined with β-lactam antibiotics shows strong synergistic antimicrobial activities against antibiotic-resistant strains of S...
July 2018: Journal of Pharmacological Sciences
Hideki Imano, Ryuji Kato, Shota Tanikawa, Fumi Yoshimura, Atsuo Nomura, Yoshio Ijiri, Takehiro Yamaguchi, Yasukatsu Izumi, Minoru Yoshiyama, Tetsuya Hayashi
Patients with obstructive sleep apnea (OSA) have a high prevalence of atrial fibrillation (AF). Rivaroxaban, a coagulation factor Xa inhibitor, has recently been reported to show pleiotropic effects. 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)...
July 2018: Journal of Pharmacological Sciences
Ken Takakura, Shouhei Takatou, Ryoichi Tomiyama, Thuong Manh Le, Dinh Thi Nguyen, Yutaka Nakamura, Tetsuya Konishi, Seiichi Matsugo, Osamu Hori
3,4-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, using RAW 264.7 cells. Lipopolysaccharide (LPS)- and interferon γ-induced production of nitrite was strongly suppressed by CAPE and, to a lesser extent, by DBL and caffeic acid ethyl ester...
July 2018: Journal of Pharmacological Sciences
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