Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02027 (Tranilast)
 205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of diarylamide derivatives were synthesized and evaluated for their inhibitory activities against human coronary artery smooth muscle cells (SMCs) and human coronary artery endothelial cells (ECs). Compound 2w was superior to the lead compound, Tranilast, in terms of the potency of the activity and cell selectivity.
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PMID:Synthesis and structure-activity relationship of diarylamide derivatives as selective inhibitors of the proliferation of human coronary artery smooth muscle cells. 1122 68

IgE-dependent histamine release from rat mesenteric mast cells was investigated. Excised mesenterium was cut into pieces and incubated with IgE overnight at 4 degrees C for sensitization. Over 10 pieces of mesenterium specimen could be prepared from a rat. Antigen-induced histamine release from mesenterium specimen was initiated rapidly and reached a plateau in 5 min. In an optimal condition, over 50% of total histamine was released. In contrast, unpurified and purified peritoneal mast cells released only 22.5% and 5.3% of total histamine, respectively, upon IgE stimulation. Tranilast, a mast cell stabilizer, inhibited the histamine release from mesenteric mast cells significantly. The mesenterium might be useful material for studying tissue-associated mast cell activation.
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PMID:High rate of IgE-mediated histamine release from rat mesenteric mast cells. 1138 25

Extensive infiltration of normal brain tissue and suppression of anti-tumor immune surveillance mediated by molecules such as transforming growth factor-beta (TGF-beta) are key biological features that contribute to the malignant phenotype of human gliomas. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an anti-allergic compound used clinically to control atopic and fibrotic disorders. These effects are attributed to the suppression of TGF-beta1 synthesis and interference with growth factor-mediated proliferation and migration of fibroblasts and vascular smooth muscle cells. Here, we show that tranilast inhibits DNA synthesis and proliferation of human malignant glioma cells and promotes p21 accumulation in the absence of cytotoxicity. Further, tranilast reduces the release of TGF-beta1 and TGF-beta2 by glioma cells and inhibits migration, chemotactic responses and invasiveness. These effects are not associated with a reduction of alpha(v)beta(3) integrin expression at the cell surface but appear to involve inhibition of matrix metalloproteinase-2 expression and activity. Neither the tranilast-mediated inhibition of proliferation nor the inhibition of migration was counteracted by supplementation with exogenous TGF-beta. Finally, tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-beta2 in vivo. We conclude that tranilast might be a useful therapeutic agent for the treatment of human malignant glioma because of a TGF-beta-independent abrogation of the malignant phenotype of proliferation, migration and invasiveness and because of the antagonism of TGF-beta-associated immunosuppression.
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PMID:N-[3,4-dimethoxycinnamoyl]-anthranilic acid (tranilast) inhibits transforming growth factor-beta relesase and reduces migration and invasiveness of human malignant glioma cells. 1139 21

Tranilast has long been used clinically to treat allergic diseases such as bronchial asthma. To further clarify the antiinflammatory machanism, we examined the ability of tranilast to counteract the prolongation of eosinophil survival induced by interleukin (IL)-5. Tranilast reduced the IL-5 prolonged survival of eosinophils at the concentration range of 30 microg/ml to 100 microg/ml. The DNA extracted from eosinophils cultured with tranilast showed signs of fragmentation that was comparable with apoptosis. Electron-microscopic analysis of activated eosinophils cultured with 100 microg/ml of tranilast also revealed morphologic features of apoptosis. These data suggest that tranilast may act in vivo on activated eosinophils to reduce inflammation in allergic diseases.
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PMID:Suppressive effect of tranilast on interleukin-5 prolonged eosinophils survival via apoptosis. 1143 Apr 66

Cardiac allograft vasculopathy is a major complication after cardiac transplantation, often limiting long-term recipient survival. N-(3,4-Dimethoxycinnamoyl)anthranilic acid (tranilast) inhibits cyclin-dependent kinase activity through p21(Waf1/Cip1) induction and arrests vascular smooth muscle cell proliferation in vitro. We tested a hypothesis that tranilast inhibits the vasculopathy characterized by diffuse intimal thickening in a murine heart transplantation model. Hearts from DBA/2 mice were heterotopically transplanted into B10.D2 mice as allografts. Oral administration of tranilast started 3 days before transplantation at doses of 550 or 1040 mg/kg per day until the animals were killed. Cardiac allograft vasculopathy was defined as luminal stenosis caused by neointimal formation. The percentage of luminal stenosis and cardiac rejection were analyzed 14 and 28 days after transplantation. Tranilast administration was associated with a marked reduction in luminal occlusion but with no significant effect on cardiac rejection. Immunohistochemical study of the tranilast-treated graft coronary arteries revealed enhancement of p21(Waf1/Cip1) and decreased expression of proliferating cell nuclear antigen in the neointima. The significant reduction in allograft vasculopathy concomitant with the enhancement of p21(Waf1/Cip1) indicates that tranilast has an antiproliferative effect that could be applicable to clinical treatment of cardiac allograft vasculopathy.
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PMID:Tranilast inhibits cardiac allograft vasculopathy in association with p21(Waf1/Cip1) expression on neointimal cells in murine cardiac transplantation model. 1145 47

Although many drug treatments have been reported to theoretically improve semen parameters in male infertility, a standard method has not been established. The authors examined whether tranilast, a mast cell blocker, improves fertility and/or semen parameters in severe oligozoospermia. Seventeen patients with a sperm density of less than 10 x 10(6) sperm/mL and their fertile partners were enrolled in this study. Patients were prescribed tranilast 300 mg/day for at least 12 weeks. Semen and blood samples were collected before and after the prescription of tranilast for 12 weeks. Semen parameters, serum gonadotropins, luteinizing hormone, follicle-stimulating hormone, serum testosterone, and testicular size were evaluated. One patient complained of mild drowsiness during treatment. The sperm count was significantly increased after administration of tranilast in 7 patients (41.1%), although sperm motility was not altered. Semen volume and normal morphology were also unaltered. Three pregnancies were achieved. Endocrine profile and testicular size were unchanged. Tranilast, a mast cell blocker, is clinically useful for the treatment of severe idiopathic oligozoospermic men.
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PMID:The treatment with tranilast, a mast cell blocker, for idiopathic oligozoospermia. 1155 81

Monocyte chemoattractant protein-1 (MCP-1), a member of the CC subfamily of chemokines, plays a crucial role in the progression of glomerulonephritis by recruitment of monocytes. Tranilast, a clinically used anti-allergic drug, has been demonstrated to have various anti-inflammatory and anti-proliferative effects, and recently has been reported to prevent restenosis after percutaneous transluminal coronary angioplasty. In this study, we investigated whether tranilast inhibits MCP-1 secretion in mesangial cells. Tranilast inhibited interleukin-1beta-induced MCP-1 secretion and mRNA expression in a concentration-dependent manner. Luciferase assay showed that tranilast suppressed interleukin-1beta-induced nuclear factor-kappaB (NF-kappaB)-dependent transcription. Interleukin-1beta-induced Jun N-terminal kinase (JNK) activation was also suppressed selectively by tranilast. These results indicate that tranilast inhibits interleukin-1beta-induced MCP-1 production, at least in part, by inhibiting NF-kappaB activity and that suppression of JNK activation might be involved in the inhibition of MCP-1 production. Tranilast may serve as a new therapeutic agent for glomerulonephritis through anti-chemokine property.
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PMID:Tranilast inhibits interleukin-1beta-induced monocyte chemoattractant protein-1 expression in rat mesangial cells. 1155 68

1. Microglial cells up-regulate inducible nitric oxide synthase (iNOS) expression in response to various pro-inflammatory stimuli including interferon-gamma (IFN-gamma), allowing for the release of nitric oxide (NO). Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) is an antiallergic compound with suppressive effects on the activation of monocytes. 2. Here, we show that N9 murine microglial cells express iNOS mRNA and protein and release nitric oxide into the culture medium in response to IFN-gamma (200 u x ml(-1)) as measured by Northern and Western blot analyses and Griess assay. 3. Exposure to non-toxic doses of tranilast (30-300 microM) leads to a concentration-dependent inhibition of IFN-gamma-induced (200 u x ml(-1)) iNOS mRNA and protein expression. This is paralleled by a suppression of NO-release into the cell culture medium. 4. Inhibition of IFN-gamma-induced iNOS mRNA expression by tranilast is paralleled by an inhibition of nuclear factor-kappaB (NF-kappaB) activation and phosphorylation of inhibitory kappaB (IkappaB) as determined by Western blot analyses and NF-kappaB reporter gene assay. 5. These results suggest that tranilast-mediated suppression of microglial iNOS activity induced by IFN-gamma involves the inhibition of NF-kappaB-dependent iNOS mRNA expression.
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PMID:N-[3,4-dimethoxycinnamoyl]-anthranilic acid (tranilast) suppresses microglial inducible nitric oxide synthase (iNOS) expression and activity induced by interferon-gamma (IFN-gamma). 1170 48

Accelerated coronary arteriosclerosis remains a major problem for the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood and there is no effective therapy. Tranilast is a promising drug that may prevent post-angioplasty restenosis. Here, we investigated whether orally administered tranilast inhibits the development of intima hyperplasia in a mouse model of cardiac transplantation. Cardiac allografts from BALB/c mice were transplanted heterotopically into C3H/He mice. Mice were administered either vehicle or tranilast everyday by gavage. Morphometrical analysis of the cardiac allografts harvested at 2 months revealed that the administration of tranilast significantly reduced the development of coronary atherosclerosis. In the mice treated with tranilast, up-regulation of the cyclin-dependent kinase inhibitor p21 was observed in the allografts, accompanied by a reduced number of proliferating cells. Tranilast also suppressed transforming growth factor-beta (TGF-beta) expression. Tranilast may be effective in preventing transplant-associated arteriosclerosis through its anti-inflammatory and anti-proliferative effects.
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PMID:Tranilast inhibits transplant-associated coronary arteriosclerosis in a murine model of cardiac transplantation. 1175 48

The present study was conducted to assess the effect of Tranilast, a drug developed as anti-keloid and anti-hypertrophic scar agent, on the level of transforming growth factor- A1 (TGF- A1) mRNA, and on TGF- A1 secretion in Chang Conjunctiva cells. TGF- A1 mRNA was not detected in Chang Conjunctiva cells by Northern blot analysis, but reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the presence of TGF- A1 mRNA. Tranilast, whereas the drug had no effect on the levels of TGF- A1 mRNA and cellular protein, time- and dose-dependently inhibited TGF- A1 secretion from Chang Conjunctiva cells in the enzyme-linked immunosorbent assay (ELISA) analysis. TGF- A1 is suggested to cause fibroblast proliferation, that obstructs aqueous humor filtration route after glaucoma filtration surgery. Tranilast, potentially inhibiting TGF- A1 secretion, therefore, could be a promising drug to prevent from scarring after glaucoma filtration surgery.
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PMID:Tranilast inhibits TGF- A1 secretion without affecting its mRNA levels in conjunctival cells. 1178 98


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