The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis
A novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and tested in vitro (LPS-activated macrophages) for its cytotoxicity and anti-inflammatory activity and in vivo (DNBS induced rat model) for...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2015/939483 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832565254577455104 |
|---|---|
| author | Dorit Moradov Helena Shifrin Efrat Harel Mirela Nadler-Milbauer Marta Weinstock Morris Srebnik Abraham Rubinstein |
| author_facet | Dorit Moradov Helena Shifrin Efrat Harel Mirela Nadler-Milbauer Marta Weinstock Morris Srebnik Abraham Rubinstein |
| author_sort | Dorit Moradov |
| collection | DOAJ |
| description | A novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and tested in vitro (LPS-activated macrophages) for its cytotoxicity and anti-inflammatory activity and in vivo (DNBS induced rat model) for its potential to ameliorate induced colitis. Specifically, the competence of P-5 to reduce TNFα, IL-6, INFγ, MCP-1, IL-1α, MIP-1α, and RANTES in LPS-activated macrophages was measured. Experimental colitis was quantified in the rat model, macroscopically and by measuring the activity of tissue MPO and iNOS and levels of TNFα and IL-1β. It was found that P-5 decreased the levels of TNFα and the tested proinflammatory cytokines and chemokines in LPS-activated macrophages. In the colitis-induced rat model, P-5 was effective locally in reducing mucosal inflammation. This activity was equal to the activity of local treatment with 5-aminosalicylic acid. It is speculated that P-5 may be used for the local treatment of IBD (e.g., with the aid of colon-specific drug platforms). Its mode of action involves inhibition of the phosphorylation of MAPK ERK but not of p38 and had no effect on IκBα. |
| format | Article |
| id | doaj-art-b426785f3fa048e69c895506d97bda68 |
| institution | Kabale University |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-b426785f3fa048e69c895506d97bda682025-02-03T01:08:54ZengWileyGastroenterology Research and Practice1687-61211687-630X2015-01-01201510.1155/2015/939483939483The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental ColitisDorit Moradov0Helena Shifrin1Efrat Harel2Mirela Nadler-Milbauer3Marta Weinstock4Morris Srebnik5Abraham Rubinstein6Faculty of Medicine, School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, IsraelFaculty of Medicine, School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, IsraelFaculty of Medicine, School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, IsraelFaculty of Medicine, School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, IsraelFaculty of Medicine, School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, IsraelFaculty of Medicine, School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, IsraelFaculty of Medicine, School of Pharmacy Institute for Drug Research, The Hebrew University of Jerusalem, P.O. Box 12065, 91120 Jerusalem, IsraelA novel fused-cyclopentenone phosphonate compound, namely, diethyl 3-nonyl-5-oxo-3,5,6,6a-tetrahydro-1H-cyclopenta[c]furan-4-ylphosphonate (P-5), was prepared and tested in vitro (LPS-activated macrophages) for its cytotoxicity and anti-inflammatory activity and in vivo (DNBS induced rat model) for its potential to ameliorate induced colitis. Specifically, the competence of P-5 to reduce TNFα, IL-6, INFγ, MCP-1, IL-1α, MIP-1α, and RANTES in LPS-activated macrophages was measured. Experimental colitis was quantified in the rat model, macroscopically and by measuring the activity of tissue MPO and iNOS and levels of TNFα and IL-1β. It was found that P-5 decreased the levels of TNFα and the tested proinflammatory cytokines and chemokines in LPS-activated macrophages. In the colitis-induced rat model, P-5 was effective locally in reducing mucosal inflammation. This activity was equal to the activity of local treatment with 5-aminosalicylic acid. It is speculated that P-5 may be used for the local treatment of IBD (e.g., with the aid of colon-specific drug platforms). Its mode of action involves inhibition of the phosphorylation of MAPK ERK but not of p38 and had no effect on IκBα.http://dx.doi.org/10.1155/2015/939483 |
| spellingShingle | Dorit Moradov Helena Shifrin Efrat Harel Mirela Nadler-Milbauer Marta Weinstock Morris Srebnik Abraham Rubinstein The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis Gastroenterology Research and Practice |
| title | The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis |
| title_full | The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis |
| title_fullStr | The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis |
| title_full_unstemmed | The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis |
| title_short | The Anti-Inflammatory Activity of a Novel Fused-Cyclopentenone Phosphonate and Its Potential in the Local Treatment of Experimental Colitis |
| title_sort | anti inflammatory activity of a novel fused cyclopentenone phosphonate and its potential in the local treatment of experimental colitis |
| url | http://dx.doi.org/10.1155/2015/939483 |
| work_keys_str_mv | AT doritmoradov theantiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT helenashifrin theantiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT efratharel theantiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT mirelanadlermilbauer theantiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT martaweinstock theantiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT morrissrebnik theantiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT abrahamrubinstein theantiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT doritmoradov antiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT helenashifrin antiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT efratharel antiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT mirelanadlermilbauer antiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT martaweinstock antiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT morrissrebnik antiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis AT abrahamrubinstein antiinflammatoryactivityofanovelfusedcyclopentenonephosphonateanditspotentialinthelocaltreatmentofexperimentalcolitis |