Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) is a highly morbid inflammatory lung disease with limited pharmacological interventions. The present study aims to evaluate and compare the potential pulmonoprotective effects of natural prolyl oligopeptidase (POP) inhibitors namely rosmarinic acid (RA), ch...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/14235 |
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| author | Stelios Zerikiotis Panagiotis Efentakis Danai Dapola Anna Agapaki Georgios Seiradakis Nikolaos Kostomitsopoulos Alexios-Leandros Skaltsounis Ioulia Tseti Filippos Triposkiadis Ioanna Andreadou |
| author_facet | Stelios Zerikiotis Panagiotis Efentakis Danai Dapola Anna Agapaki Georgios Seiradakis Nikolaos Kostomitsopoulos Alexios-Leandros Skaltsounis Ioulia Tseti Filippos Triposkiadis Ioanna Andreadou |
| author_sort | Stelios Zerikiotis |
| collection | DOAJ |
| description | Acute respiratory distress syndrome (ARDS) is a highly morbid inflammatory lung disease with limited pharmacological interventions. The present study aims to evaluate and compare the potential pulmonoprotective effects of natural prolyl oligopeptidase (POP) inhibitors namely rosmarinic acid (RA), chicoric acid (CA), epigallocatechin-3-gallate (EGCG) and gallic acid (GA), against lipopolysaccharide (LPS)-induced ARDS. Cell viability and expression of pro-inflammatory mediators were measured in RAW264.7 cells and in primary murine lung epithelial and bone marrow cells. Nitric oxide (NO) production was also assessed in unstimulated and LPS-stimulated RAW264.7 cells. For subsequent in vivo experiments, the two natural products (NPs) with the most favorable effects, RA and GA, were selected. Protein, cell content and lipid peroxidation levels in bronchoalveolar lavage fluid (BALF), as well as histopathological changes and respiratory parameters were evaluated in LPS-challenged mice. Expression of key mediators involved in ARDS pathophysiology was detected by Western blotting. RA and GA favorably reduced gene expression of pro-inflammatory mediators in vitro, while GA decreased NO production in macrophages. In LPS-challenged mice, RA and GA co-administration improved respiratory parameters, reduced cell and protein content and malondialdehyde (MDA) levels in BALF, decreased vascular cell adhesion molecule-1 (VCAM-1) and the inducible nitric oxide synthase (iNOS) protein expression, activated anti-apoptotic mechanisms and down-regulated POP in the lung. Conclusively, these synergistic pulmonoprotective effects of RA and GA co-administration could render them a promising prophylactic/therapeutic pharmacological intervention against ARDS. |
| first_indexed | 2024-03-10T22:39:52Z |
| format | Article |
| id | doaj.art-ff6c357abeab4d42aaf0baa718a22653 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:39:52Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ff6c357abeab4d42aaf0baa718a226532023-11-19T11:09:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181423510.3390/ijms241814235Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress SyndromeStelios Zerikiotis0Panagiotis Efentakis1Danai Dapola2Anna Agapaki3Georgios Seiradakis4Nikolaos Kostomitsopoulos5Alexios-Leandros Skaltsounis6Ioulia Tseti7Filippos Triposkiadis8Ioanna Andreadou9Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 157 71 Athens, GreeceLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 157 71 Athens, GreeceLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 157 71 Athens, GreeceHistochemistry Facility, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, GreeceLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 157 71 Athens, GreeceLaboratory Animal Facility, Centre of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, GreeceSection of Pharmacognosy and Natural Product Chemistry Faculty of Pharmacy, National and Kapodistrian University of Athens, 157 71 Athens, GreeceUni-Pharma S.A., 145 64 Athens, GreeceDepartment of Cardiology, University General Hospital of Larissa, 413 34 Larissa, GreeceLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 157 71 Athens, GreeceAcute respiratory distress syndrome (ARDS) is a highly morbid inflammatory lung disease with limited pharmacological interventions. The present study aims to evaluate and compare the potential pulmonoprotective effects of natural prolyl oligopeptidase (POP) inhibitors namely rosmarinic acid (RA), chicoric acid (CA), epigallocatechin-3-gallate (EGCG) and gallic acid (GA), against lipopolysaccharide (LPS)-induced ARDS. Cell viability and expression of pro-inflammatory mediators were measured in RAW264.7 cells and in primary murine lung epithelial and bone marrow cells. Nitric oxide (NO) production was also assessed in unstimulated and LPS-stimulated RAW264.7 cells. For subsequent in vivo experiments, the two natural products (NPs) with the most favorable effects, RA and GA, were selected. Protein, cell content and lipid peroxidation levels in bronchoalveolar lavage fluid (BALF), as well as histopathological changes and respiratory parameters were evaluated in LPS-challenged mice. Expression of key mediators involved in ARDS pathophysiology was detected by Western blotting. RA and GA favorably reduced gene expression of pro-inflammatory mediators in vitro, while GA decreased NO production in macrophages. In LPS-challenged mice, RA and GA co-administration improved respiratory parameters, reduced cell and protein content and malondialdehyde (MDA) levels in BALF, decreased vascular cell adhesion molecule-1 (VCAM-1) and the inducible nitric oxide synthase (iNOS) protein expression, activated anti-apoptotic mechanisms and down-regulated POP in the lung. Conclusively, these synergistic pulmonoprotective effects of RA and GA co-administration could render them a promising prophylactic/therapeutic pharmacological intervention against ARDS.https://www.mdpi.com/1422-0067/24/18/14235acute respiratory distress syndromelipopolysaccharidenatural productsrosmarinic acidchicoric acidepigallocatechin-3-gallate |
| spellingShingle | Stelios Zerikiotis Panagiotis Efentakis Danai Dapola Anna Agapaki Georgios Seiradakis Nikolaos Kostomitsopoulos Alexios-Leandros Skaltsounis Ioulia Tseti Filippos Triposkiadis Ioanna Andreadou Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress Syndrome International Journal of Molecular Sciences acute respiratory distress syndrome lipopolysaccharide natural products rosmarinic acid chicoric acid epigallocatechin-3-gallate |
| title | Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress Syndrome |
| title_full | Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress Syndrome |
| title_fullStr | Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress Syndrome |
| title_full_unstemmed | Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress Syndrome |
| title_short | Synergistic Pulmonoprotective Effect of Natural Prolyl Oligopeptidase Inhibitors in In Vitro and In Vivo Models of Acute Respiratory Distress Syndrome |
| title_sort | synergistic pulmonoprotective effect of natural prolyl oligopeptidase inhibitors in in vitro and in vivo models of acute respiratory distress syndrome |
| topic | acute respiratory distress syndrome lipopolysaccharide natural products rosmarinic acid chicoric acid epigallocatechin-3-gallate |
| url | https://www.mdpi.com/1422-0067/24/18/14235 |
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