Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice
Acute lung injury (ALI) represents a life-threatening condition with high morbidity and mortality despite modern mechanical ventilators and multiple pharmacological strategies. Therefore, there is a need to develop efficacious interventions with minimal side effects. The anti-inflammatory activities...
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MDPI AG
2024-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/7/1511 |
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| author | Oladapo F. Fagbohun Wasitha P. D. W. Thilakarathna Juan Zhou Christian Lehmann Guangling Jiao H. P. Vasantha Rupasinghe |
| author_facet | Oladapo F. Fagbohun Wasitha P. D. W. Thilakarathna Juan Zhou Christian Lehmann Guangling Jiao H. P. Vasantha Rupasinghe |
| author_sort | Oladapo F. Fagbohun |
| collection | DOAJ |
| description | Acute lung injury (ALI) represents a life-threatening condition with high morbidity and mortality despite modern mechanical ventilators and multiple pharmacological strategies. Therefore, there is a need to develop efficacious interventions with minimal side effects. The anti-inflammatory activities of sea cucumber (<i>Cucumaria frondosa</i>) and wild blueberry (<i>Vaccinium angustifolium</i>) extracts have been reported recently. However, their anti-inflammatory activities and the mechanism of action against ALI are not fully elucidated. Thus, the present study aims to understand the mechanism of the anti-inflammatory activity of sea cucumber and wild blueberry extracts in the context of ALI. Experimental ALI was induced via intranasal lipopolysaccharide (LPS) instillation in C57BL/6 mice and the anti-inflammatory properties were determined by cytokine analysis, histological examination, western blot, and qRT-PCR. The results showed that oral supplementation of sea cucumber extracts repressed nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby downregulating the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) in the lung tissue and in the plasma. Wild blueberry extracts also suppressed the expression of IL-4. Furthermore, the combination of sea cucumber and wild blueberry extracts restrained MAPK signaling pathways by prominent attenuation of phosphorylation of NF-κB, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) while the levels of pro-inflammatory cytokines were significantly suppressed. Moreover, there was a significant and synergistic reduction in varying degrees of ALI lesions such as distorted parenchyma, increased alveoli thickness, lymphocyte and neutrophil infiltrations, fibrin deposition, pulmonary emphysema, pneumonia, intra-alveolar hemorrhage, and edema. The anti-inflammatory effect of the combination of sea cucumber and wild blueberry extracts is associated with suppressing MAPK and NF-κB signaling pathways, thereby significantly reducing cytokine storm in LPS-induced experimental ALI. |
| first_indexed | 2024-04-24T10:38:59Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-24T10:38:59Z |
| publishDate | 2024-03-01 |
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| spelling | doaj.art-51a7718b60cc418c9970ddd306e0ba3c2024-04-12T13:23:15ZengMDPI AGMolecules1420-30492024-03-01297151110.3390/molecules29071511Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 MiceOladapo F. Fagbohun0Wasitha P. D. W. Thilakarathna1Juan Zhou2Christian Lehmann3Guangling Jiao4H. P. Vasantha Rupasinghe5Department Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, CanadaDepartment Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, CanadaDepartments of Anaesthesia, Pain Management and Perioperative Medicine, Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartments of Anaesthesia, Pain Management and Perioperative Medicine, Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Process Engineering and Applied Science, Faculty of Engineering, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, CanadaAcute lung injury (ALI) represents a life-threatening condition with high morbidity and mortality despite modern mechanical ventilators and multiple pharmacological strategies. Therefore, there is a need to develop efficacious interventions with minimal side effects. The anti-inflammatory activities of sea cucumber (<i>Cucumaria frondosa</i>) and wild blueberry (<i>Vaccinium angustifolium</i>) extracts have been reported recently. However, their anti-inflammatory activities and the mechanism of action against ALI are not fully elucidated. Thus, the present study aims to understand the mechanism of the anti-inflammatory activity of sea cucumber and wild blueberry extracts in the context of ALI. Experimental ALI was induced via intranasal lipopolysaccharide (LPS) instillation in C57BL/6 mice and the anti-inflammatory properties were determined by cytokine analysis, histological examination, western blot, and qRT-PCR. The results showed that oral supplementation of sea cucumber extracts repressed nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby downregulating the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) in the lung tissue and in the plasma. Wild blueberry extracts also suppressed the expression of IL-4. Furthermore, the combination of sea cucumber and wild blueberry extracts restrained MAPK signaling pathways by prominent attenuation of phosphorylation of NF-κB, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) while the levels of pro-inflammatory cytokines were significantly suppressed. Moreover, there was a significant and synergistic reduction in varying degrees of ALI lesions such as distorted parenchyma, increased alveoli thickness, lymphocyte and neutrophil infiltrations, fibrin deposition, pulmonary emphysema, pneumonia, intra-alveolar hemorrhage, and edema. The anti-inflammatory effect of the combination of sea cucumber and wild blueberry extracts is associated with suppressing MAPK and NF-κB signaling pathways, thereby significantly reducing cytokine storm in LPS-induced experimental ALI.https://www.mdpi.com/1420-3049/29/7/1511<i>Cucumaria frondosa</i><i>Vaccinium angustifolium</i>ALIcytokineinflammationNF-κB |
| spellingShingle | Oladapo F. Fagbohun Wasitha P. D. W. Thilakarathna Juan Zhou Christian Lehmann Guangling Jiao H. P. Vasantha Rupasinghe Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice Molecules <i>Cucumaria frondosa</i> <i>Vaccinium angustifolium</i> ALI cytokine inflammation NF-κB |
| title | Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice |
| title_full | Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice |
| title_fullStr | Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice |
| title_full_unstemmed | Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice |
| title_short | Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-κB/MAPK/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL/6 Mice |
| title_sort | sea cucumber and blueberry extracts suppress inflammation and reduce acute lung injury through the regulation of nf κb mapk jnk signaling pathway in lipopolysaccharide treated c57bl 6 mice |
| topic | <i>Cucumaria frondosa</i> <i>Vaccinium angustifolium</i> ALI cytokine inflammation NF-κB |
| url | https://www.mdpi.com/1420-3049/29/7/1511 |
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