Alleviating effects of AS1892802, a Rho kinase inhibitor, on osteoarthritic disorders in rodents.


:The effects of AS1892802, a selective Rho-associated coiled coil kinase (ROCK) inhibitor, on knee cartilage damage and pain behavior were examined in a rat model of osteoarthritis (OA). Monoiodoacetate (MIA) was intraarticularly injected into the right knee joints of rats. ROCK I and II mRNA levels increased in knee joints of MIA-injected rats. Our newly synthesized ROCK inhibitor, AS1892802, was injected into the ipsilateral knee or administered p.o. for 3 weeks. The compound dose-dependently and significantly inhibited of cartilage damage in the tibial plateau in a dose-dependent manner and decreased the weight distribution deficit associated with MIA injection. In addition, the compound also inhibited bradykinin induced pain responses in normal rats. In vitro, the compound could induce chondrocyte differentiation in a chondrogenic cell line and significantly inhibited IL-1β- or bradykinin-induced prostaglandin E(2) production in a synovial cell line. AS1892802 prevents cartilage damage induced by MIA and has analgesic effects in rat pain models, suggesting that AS1892802 may be clinically useful for the treatment of OA.[Supplementary Figure: available only at].


J Pharmacol Sci


Takeshita N,Yoshimi E,Hatori C,Kumakura F,Seki N,Shimizu Y




Has Abstract


2011-01-01 00:00:00














  • Estrogenic compound attenuates angiotensin II-induced vascular smooth muscle cell proliferation through interaction between LKB1 and estrogen receptor α.

    abstract::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 V...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Kim SA,Lee KY,Kim JR,Choi HC

    更新日期:2016-09-01 00:00:00

  • A perspective on metabolic surgery from a gastroenterologist.

    abstract::Type 2 diabetes (T2D) and obesity are important public health problems. The global prevalence of diabetes mellitus is 8.8%. Interventional diabetology and obesitology have been recently advocated as treatment options for T2D and obesity. The roles of metabolic surgery such as Roux-en-Y gastric bypass, sleeve gastrecto...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Syu YF,Inui A,Chen CY

    更新日期:2017-02-01 00:00:00

  • Neuroprotective effects of methyl 3,4-dihydroxybenzoate against H₂O₂-induced apoptosis in RGC-5 cells.

    abstract::In the present study, we investigated the protective effect of methyl 3,4-dihydroxybenzoate (MDHB) against H2O2-induced apoptosis in RGC-5 cells. The RGC-5 cells were cultured in plates for 24 h, which were then pretreated with dimethyl sulfoxide, different concentrations of MDHB, or probucol for 12 h prior to additio...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Zhou X,Su CF,Zhang Z,Wang CY,Luo JQ,Zhou XW,Cai L,Yan L,Zhang W,Luo HM

    更新日期:2014-01-01 00:00:00

  • New methods to evaluate endothelial function: A search for a marker of nitric oxide (NO) in vivo: re-evaluation of NOx in plasma and red blood cells and a trial to detect nitrosothiols.

    abstract::Although plasma NOx (NO(2)(-) and NO(3)(-)) has been used as an index of nitric oxide (NO) formation in vivo, many unreasonable results appeared even after active elimination of NOx contamination from laboratory ware. For example, plasma NOx concentrations did not increase during vasodilation mediated by the NO/cGMP p...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Ishibashi T,Yoshida J,Nishio M

    更新日期:2003-12-01 00:00:00

  • Enhanced expression of glutathione S-transferase in the hippocampus following acute treatment with trimethyltin in vivo.

    abstract::We investigated the effects of treatment with trimethyltin (TMT) on the expression of glutathione-related enzymes in mouse hippocampus. TMT promoted the expression of glutathione S-transferase (GST) Ya/Yc mRNA, and GSTA2 protein, but not that of glutamate-cysteine ligase catalytic subunit mRNA, 1 day after injection. ...

    journal_title:Journal of pharmacological sciences

    pub_type: 历史文章,杂志文章


    authors: Nagashima R,Sano S,Huong NQ,Shiba T,Ogita K

    更新日期:2010-01-01 00:00:00

  • Progress in allergy signal research on mast cells: systemic approach to mast cell biology in allergic diseases.

    abstract::At the end of the last century, microarray technology that examines the total genes and transcripts present in a cell became available as a laboratory tool. Mast cells are known to play a pivotal role in initiating allergic inflammation by releasing various mediators and cytokines. According to the recent microarray-b...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Saito H

    更新日期:2008-03-01 00:00:00

  • The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses isolation rearing-induced abnormal behaviors in mice.

    abstract::Isolation-induced abnormal behaviors are useful animal models for assessing potential anti-psychotic drugs. This study examined the effect of MGS0028, a selective metabotropic glutamate 2/3 receptor agonist, on abnormal behaviors such as hyperactivity, aggression, and deficits of prepulse inhibition in isolation-reare...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Ago Y,Araki R,Yano K,Kawasaki T,Chaki S,Nakazato A,Onoe H,Hashimoto H,Baba A,Takuma K,Matsuda T

    更新日期:2012-01-01 00:00:00

  • Establishment and characterization of mammalian cell lines stably expressing human L-type amino acid transporters.

    abstract::System L (SL), a basolateral amino acid transporter, transports large neutral amino acids (LNAAs) in a Na(+)-independent manner. Previously, we identified two isoforms of transporters: L-type amino acid transporter 1 (LAT1) and 2 (LAT2) and revealed their distinct substrate selectivity and transport properties. In thi...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Morimoto E,Kanai Y,Kim DK,Chairoungdua A,Choi HW,Wempe MF,Anzai N,Endou H

    更新日期:2008-12-01 00:00:00

  • Forced exercise-induced flushing of tail skin in ovariectomized mice, as a new experimental model of menopausal hot flushes.

    abstract::Hot flushes are the most common complaint of menopausal women. In the present study, a new animal model of hot flushes was established. Tail skin temperature was measured with a thermo tracer after mice were subjected to a forced exercise task using a motor driven treadmill. In ovariectomized mice, forced exercise for...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Shuto H,Yamauchi A,Ikeda M,Sohda Y,Koga A,Tominaga K,Egawa T,Kataoka Y

    更新日期:2005-07-01 00:00:00

  • Mithramycin, an agent for developing new therapeutic drugs for neurodegenerative diseases.

    abstract::Mithramycin A (MTM) has been shown to inhibit cancer growth by blocking the binding of Sp-family transcription factors to gene regulatory elements and is used for the treatment of leukemia and testicular cancer in the United States. In contrast, MTM has also been shown to exert neuroprotective effects in normal cells....

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Osada N,Kosuge Y,Ishige K,Ito Y

    更新日期:2013-01-01 00:00:00

  • Endothelial progenitor cells: therapeutic target for cardiovascular diseases.

    abstract::Circulating endothelial progenitor cells (EPCs) derived from bone marrow were isolated for the first time in 1997 and characterized. Recent evidence has indicated that EPCs contribute to re-endothelialization of injured vessels as well as neovascularization of ischemic lesions and that a decrease in the number of EPCs...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Umemura T,Higashi Y

    更新日期:2008-09-01 00:00:00

  • Intracerebroventricular injection of microglia protects against focal brain ischemia.

    abstract::Microglia are macrophage-like phagocytic cells in the brain parenchyma. However, microglial function after neurodegeneration is not fully understood. In this study, occlusion of the middle cerebral artery (MCA) and reperfusion caused massive neuronal loss in the rat cerebral cortex and striatum after 3 days. When exog...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Kitamura Y,Takata K,Inden M,Tsuchiya D,Yanagisawa D,Nakata J,Taniguchi T

    更新日期:2004-02-01 00:00:00

  • Factor Xa inhibition by rivaroxaban attenuates cardiac remodeling due to intermittent hypoxia.

    abstract::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 C5...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Imano H,Kato R,Tanikawa S,Yoshimura F,Nomura A,Ijiri Y,Yamaguchi T,Izumi Y,Yoshiyama M,Hayashi T

    更新日期:2018-07-01 00:00:00

  • Effects of mosapride citrate, a 5-HT4-receptor agonist, on gastric distension-induced visceromotor response in conscious rats.

    abstract::Mosapride citrate (mosapride), a prokinetic agent with 5-HT(4)-receptor agonistic activity, is known to enhance gastric emptying and alleviate symptoms in patients with functional dyspepsia (FD). As hyperalgesia and delayed gastric emptying play an important role in the pathogenesis of FD, we used in this study balloo...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Seto Y,Yoshida N,Kaneko H

    更新日期:2011-01-01 00:00:00

  • Antidepressant-like effect of venlafaxine is abolished in μ-opioid receptor-knockout mice.

    abstract::Although the opioid system is known to modulate depression-like behaviors, its role in the effects of antidepressants is not yet clear. We investigated the role of μ-opioid receptors (MOPs) in the effects of venlafaxine, a serotonin and norepinephrine reuptake inhibitor, in the forced swim test using MOP-knockout (KO)...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Ide S,Fujiwara S,Fujiwara M,Sora I,Ikeda K,Minami M,Uhl GR,Ishihara K

    更新日期:2010-01-01 00:00:00

  • The novel compounds that activate farnesoid X receptor: the diversity of their effects on gene expression.

    abstract::Farnesoid X receptor (FXR) controls the expression of critical genes in bile acid and cholesterol homeostasis. To study FXR and to develop a regulator of cholesterol, some non-steroidal and steroidal ligands have been found in addition to endogenous ligands for FXR. In this study, we discovered five bile acid derivati...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Suzuki T,Tamehiro N,Sato Y,Kobayashi T,Ishii-Watabe A,Shinozaki Y,Nishimaki-Mogami T,Hashimoto T,Asakawa Y,Inoue K,Ohno Y,Yamaguchi T,Kawanishi T

    更新日期:2008-07-01 00:00:00

  • Discovery of a novel chalcone derivative inhibiting CFTR chloride channel via AMPK activation and its anti-diarrheal application.

    abstract::Secretory diarrhea is one of the most common causes of death world-wide especially in children under 5 years old. Isoliquiritigenin (ISLQ), a plant-derived chalcone, has previously been shown to exert anti-secretory action in vitro and in vivo by inhibiting CFTR Cl- channels. However, its CFTR inhibition potency is co...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Yibcharoenporn C,Chusuth P,Jakakul C,Rungrotmongkol T,Chavasiri W,Muanprasat C

    更新日期:2019-07-01 00:00:00

  • Cyclic ADP-ribose mediates formyl methionyl leucyl phenylalanine (fMLP)-induced intracellular Ca(2+) rise and migration of human neutrophils.

    abstract::Although cyclic ADP-ribose (cADPR), a novel Ca(2+)-mobilizing mediator, is suggested to be involved in the functions of neutrophils in rodents, its role in human neutrophils remains unclear. The present study examined the ability of cADPR to mobilize Ca(2+) and mediate formyl methionyl leucyl phenylalanine (fMLP)-stim...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Morita K,Saida M,Morioka N,Kitayama T,Akagawa Y,Dohi T

    更新日期:2008-03-01 00:00:00

  • The systemic bone protective effects of Gushukang granules in ovariectomized mice by inhibiting osteoclastogenesis and stimulating osteoblastogenesis.

    abstract::Primary osteoporosis (POP), which is caused by unbalanced bone remodeling, leads to significant economic and societal burdens globally. Gushukang (GSK) granule serves as one commonly used prescription for POP in Traditional Chinese Medicine (TCM). The present study aimed to clarify the exact roles of GSK in bone remod...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Wang Q,Zhao Y,Sha N,Zhang Y,Li C,Zhang H,Tang D,Lu S,Shi Q,Wang Y,Shu B,Zhao D

    更新日期:2018-03-01 00:00:00

  • Cucurbitacin B induces inhibitory effects via the CIP2A/PP2A/C-KIT signaling axis in t(8;21) acute myeloid leukemia.

    abstract::Acute myeloid leukemia (AML) is the most common subtype of hematological malignancy in humans, and its incidence increases with age. The treatment of AML still faces challenges. Therefore, there is an urgent need to develop more effective targeted therapies. The receptor tyrosine kinase C-KIT confers critical prolifer...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Ma W,Xiang Y,Yang R,Zhang T,Xu J,Wu Y,Liu X,Xiang K,Zhao H,Liu Y,Si Y

    更新日期:2019-04-01 00:00:00

  • Nicotinic acetylcholine receptor alpha7 subunit mediates migration of vascular smooth muscle cells toward nicotine.

    abstract::GbaSM-4 cells, vascular smooth muscle cells (VSMCs) derived from brain basilar arteries, were shown to migrate toward d-nicotine by augmenting the actin cytoskeleton in their cell bodies and lamellipodia, and expression of nicotinic acetylcholine receptor (alpha7-nAChR) was detected in GbaSM-4 cells. Their chemotaxis ...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Li S,Zhao T,Xin H,Ye LH,Zhang X,Tanaka H,Nakamura A,Kohama K

    更新日期:2004-03-01 00:00:00

  • Decrease in the kainate-induced wet dog shake behavior in genetically epilepsy-prone rats: possible involvement of an impaired synaptic transmission to the 5-HT(2A) receptor.

    abstract::Genetically epilepsy-prone rats (GEPR-9s) were derived from Sprague-Dawley rats (SD). The number of kainate-induced wet dog shake behavior (WDS) responses was found to decrease significantly in GEPR-9s compared to SD. WDS responses were potentiated by 5-hydroxytryptophan or 2,5-dimethoxy-4-iodoamphetamine and antagoni...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Shin EJ,Jeong JH,Chung YH,Kim TW,Shin CY,Kim WK,Ko KH,Kim HC

    更新日期:2009-07-01 00:00:00

  • Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer's disease.

    abstract::Alzheimer's disease (AD) is the most common neurodegenerative disorder of late life characterized by insidious, chronic, and progressive memory impairment in association with the accumulation of senile plaques, neurofibrillary tangles, and massive loss of neurons. Apoptosis is believed to be an important contributor t...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Takuma K,Yan SS,Stern DM,Yamada K

    更新日期:2005-03-01 00:00:00

  • History of the G protein-coupled receptor (GPCR) assays from traditional to a state-of-the-art biosensor assay.

    abstract::The G protein-coupled receptors (GPCRs) form the largest and the most versatile superfamily that share a seven-transmembrane-spanning architecture. GPCR-signaling is involved in vision, taste, olfaction, sympathetic/parasympathetic nervous functions, metabolism, and immune regulation, indicating that GPCRs are extreme...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Miyano K,Sudo Y,Yokoyama A,Hisaoka-Nakashima K,Morioka N,Takebayashi M,Nakata Y,Higami Y,Uezono Y

    更新日期:2014-01-01 00:00:00

  • Myricetin ameliorated ischemia/reperfusion-induced brain endothelial permeability by improvement of eNOS uncoupling and activation eNOS/NO.

    abstract::Disruption of the blood-brain barrier (BBB) has been considered as a major pathological change in stroke. eNOS/NO play a key role in maintain BBB function. Myricetin is one of the common flavones widely exists in food and fruit, show certain protective effect on the brain function. This experiment establishes oxygeneg...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Zhang S,Hu X,Guo S,Shi L,He Q,Zhang P,Yu S,Zhao R

    更新日期:2019-05-01 00:00:00

  • LX0702, a novel snake venom peptide derivative, inhibits thrombus formation via affecting the binding of fibrinogen with GPIIb/IIIa.

    abstract::Based on the structure of AAP, a novel anti-thrombotic peptide from snake venom which we discovered in our previous study, more than 60 compounds were designed and synthesized. One of these termed as LX0702 exhibited stronger anti-platelet aggregation activity than AAP. This study aims to investigate the effects of LX...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Kong Y,Wang Y,Yang W,Xie Z,Li Z

    更新日期:2015-04-01 00:00:00

  • Transcriptional regulation of neuronal genes and its effect on neural functions: transcriptional regulation of neuropeptide Y gene by leptin and its effect on feeding.

    abstract::Leptin is an adipose tissue-derived secretory hormone that suppresses appetite by inhibition of neuropepeptide Y (NPY) gene expression in arcuate nucleus (ARC) in the hypothalamus. To investigate the transcriptional regulation of NPY gene by leptin, we carried out a luciferase assay using NPY gene promotor plasmid (NP...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Higuchi H,Hasegawa A,Yamaguchi T

    更新日期:2005-07-01 00:00:00

  • Involvement of endothelin and ET(A) endothelin receptor in mechanical allodynia in mice given orthotopic melanoma inoculation.

    abstract::We investigated whether endothelin (ET) would be involved in skin cancer pain in mice. Orthotopic inoculation of B16-BL6 melanoma cells into the plantar region of the hind paw produced marked mechanical allodynia in C57BL/6 mice. Intraplantar injections of the ET(A)-receptor antagonist BQ-123 (0.3 - 3 nmol/site), but ...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Fujita M,Andoh T,Saiki I,Kuraishi Y

    更新日期:2008-02-01 00:00:00

  • AT-406, an IAP inhibitor, activates apoptosis and induces radiosensitization of normoxic and hypoxic cervical cancer cells.

    abstract::IAP antagonists increased the antitumor efficacy of X-irradiation in some types of cancers, but their effects on hypoxic cancer cells remain unclarified. We aims to investigate the radiosensitizing effect of an IAP inhibitor AT-406 on cervical cancer cell lines under both normoxia and hypoxia conditions. Hela and Siha...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Lu J,Qin Q,Zhan LL,Liu J,Zhu HC,Yang X,Zhang C,Xu LP,Liu ZM,Wang D,Cui HQ,Meng CC,Cai J,Cheng HY,Sun XC

    更新日期:2014-01-01 00:00:00

  • Pilot study of topical delivery of mono-L-aspartyl chlorin e6 (NPe6): implication of topical NPe6-photodynamic therapy.

    abstract::Photodynamic therapy (PDT) is an evolving cancer treatment with promising results in treating malignant tumors by photoactivation of a photosensitizer with a specific wavelength. The second generation photosensitizer mono-L-aspartyl chlorin e6 (NPe6) was reported to have significant efficacy in killing cancer cells in...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章


    authors: Wong TW,Aizawa K,Sheyhedin I,Wushur C,Kato H

    更新日期:2003-10-01 00:00:00