{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:55:22Z","timestamp":1791928522184,"version":"4.3.4"},"reference-count":80,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mitacs","award":["IT25886"],"award-info":[{"award-number":["IT25886"]}]},{"name":"AKSO Marine Biotech Inc., Halifax, NS, Canada","award":["IT25886"],"award-info":[{"award-number":["IT25886"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 (Cucumaria frondosa) and wild blueberry (Vaccinium angustifolium) 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-\u03baB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby downregulating the expression of interleukin (IL)-1\u03b2, 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-\u03baB, 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-\u03baB signaling pathways, thereby significantly reducing cytokine storm in LPS-induced experimental ALI.<\/jats:p>","DOI":"10.3390\/molecules29071511","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T12:09:40Z","timestamp":1711627780000},"page":"1511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Sea Cucumber and Blueberry Extracts Suppress Inflammation and Reduce Acute Lung Injury through the Regulation of NF-\u03baB\/MAPK\/JNK Signaling Pathway in Lipopolysaccharide-Treated C57BL\/6 Mice"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1340-6697","authenticated-orcid":false,"given":"Oladapo F.","family":"Fagbohun","sequence":"first","affiliation":[{"name":"Department Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada"},{"name":"Department of Biology, Center for Agriculture and Sciences, Wilmington College, 1870 Quaker Way, Wilmington, OH 45177, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2835-8819","authenticated-orcid":false,"given":"Wasitha P. D. W.","family":"Thilakarathna","sequence":"additional","affiliation":[{"name":"Department Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-0238","authenticated-orcid":false,"given":"Juan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of Anaesthesia, Pain Management and Perioperative Medicine, Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-9168","authenticated-orcid":false,"given":"Christian","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Departments of Anaesthesia, Pain Management and Perioperative Medicine, Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangling","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Process Engineering and Applied Science, Faculty of Engineering, Dalhousie University, Halifax, NS B3H 4R2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-0052","authenticated-orcid":false,"given":"H. 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