N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism
Similar to canine inflammatory enteropathy, inflammatory bowel disease (IBD) is a chronic idiopathic condition characterized by remission periods and recurrent flares in which diarrhea, visceral pain, rectal bleeding/bloody stools, and weight loss are the main clinical symptoms. Intestinal barrier f...
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MDPI AG
2022-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/8/1163 |
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| author | Irene Palenca Luisa Seguella Alessandro Del Re Silvia Basili Franzin Chiara Corpetti Marcella Pesce Sara Rurgo Luca Steardo Giovanni Sarnelli Giuseppe Esposito |
| author_facet | Irene Palenca Luisa Seguella Alessandro Del Re Silvia Basili Franzin Chiara Corpetti Marcella Pesce Sara Rurgo Luca Steardo Giovanni Sarnelli Giuseppe Esposito |
| author_sort | Irene Palenca |
| collection | DOAJ |
| description | Similar to canine inflammatory enteropathy, inflammatory bowel disease (IBD) is a chronic idiopathic condition characterized by remission periods and recurrent flares in which diarrhea, visceral pain, rectal bleeding/bloody stools, and weight loss are the main clinical symptoms. Intestinal barrier function alterations often persist in the remission phase of the disease without ongoing inflammatory processes. However, current therapies include mainly anti-inflammatory compounds that fail to promote functional symptoms-free disease remission, urging new drug discoveries to handle patients during this step of the disease. ALIAmides (ALIA, autacoid local injury antagonism) are bioactive fatty acid amides that recently gained attention because of their involvement in the control of inflammatory response, prompting the use of these molecules as plausible therapeutic strategies in the treatment of several chronic inflammatory conditions. N-palmitoyl-D-glucosamine (PGA), an under-researched ALIAmide, resulted in being safe and effective in preclinical models of inflammation and pain, suggesting its potential engagement in the treatment of IBD. In our study, we demonstrated that micronized PGA significantly and dose-dependently reduces colitis severity, improves intestinal mucosa integrity by increasing the tight junction proteins expression, and downregulates the TLR-4/NLRP3/iNOS pathway via PPAR-α receptors signaling in DNBS-treated mice. The possibility of clinically exploiting micronized PGA as support for the treatment and prevention of inflammation-related changes in IBD patients would represent an innovative, effective, and safe strategy. |
| first_indexed | 2024-03-09T10:00:22Z |
| format | Article |
| id | doaj.art-5422be949a56421c867fe54cc420647c |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T10:00:22Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5422be949a56421c867fe54cc420647c2023-12-01T23:29:30ZengMDPI AGBiomolecules2218-273X2022-08-01128116310.3390/biom12081163N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent MechanismIrene Palenca0Luisa Seguella1Alessandro Del Re2Silvia Basili Franzin3Chiara Corpetti4Marcella Pesce5Sara Rurgo6Luca Steardo7Giovanni Sarnelli8Giuseppe Esposito9Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Psychiatry, Giustino Fortunato University, 82100 Benevento, ItalyDepartment of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, ItalyDepartment of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, ItalySimilar to canine inflammatory enteropathy, inflammatory bowel disease (IBD) is a chronic idiopathic condition characterized by remission periods and recurrent flares in which diarrhea, visceral pain, rectal bleeding/bloody stools, and weight loss are the main clinical symptoms. Intestinal barrier function alterations often persist in the remission phase of the disease without ongoing inflammatory processes. However, current therapies include mainly anti-inflammatory compounds that fail to promote functional symptoms-free disease remission, urging new drug discoveries to handle patients during this step of the disease. ALIAmides (ALIA, autacoid local injury antagonism) are bioactive fatty acid amides that recently gained attention because of their involvement in the control of inflammatory response, prompting the use of these molecules as plausible therapeutic strategies in the treatment of several chronic inflammatory conditions. N-palmitoyl-D-glucosamine (PGA), an under-researched ALIAmide, resulted in being safe and effective in preclinical models of inflammation and pain, suggesting its potential engagement in the treatment of IBD. In our study, we demonstrated that micronized PGA significantly and dose-dependently reduces colitis severity, improves intestinal mucosa integrity by increasing the tight junction proteins expression, and downregulates the TLR-4/NLRP3/iNOS pathway via PPAR-α receptors signaling in DNBS-treated mice. The possibility of clinically exploiting micronized PGA as support for the treatment and prevention of inflammation-related changes in IBD patients would represent an innovative, effective, and safe strategy.https://www.mdpi.com/2218-273X/12/8/1163micronized N-palmitoyl-D-glucosamineulcerative colitisIBDintestinal inflammationtoll-like receptorsPPARs |
| spellingShingle | Irene Palenca Luisa Seguella Alessandro Del Re Silvia Basili Franzin Chiara Corpetti Marcella Pesce Sara Rurgo Luca Steardo Giovanni Sarnelli Giuseppe Esposito N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism Biomolecules micronized N-palmitoyl-D-glucosamine ulcerative colitis IBD intestinal inflammation toll-like receptors PPARs |
| title | N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism |
| title_full | N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism |
| title_fullStr | N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism |
| title_full_unstemmed | N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism |
| title_short | N-Palmitoyl-D-Glucosamine Inhibits TLR-4/NLRP3 and Improves DNBS-Induced Colon Inflammation through a PPAR-α-Dependent Mechanism |
| title_sort | n palmitoyl d glucosamine inhibits tlr 4 nlrp3 and improves dnbs induced colon inflammation through a ppar α dependent mechanism |
| topic | micronized N-palmitoyl-D-glucosamine ulcerative colitis IBD intestinal inflammation toll-like receptors PPARs |
| url | https://www.mdpi.com/2218-273X/12/8/1163 |
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