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As a result, the present study was designed to investigate the in vivo effects of LH-6 on cyclophosphamide-induced immunodeficient mice. The results demonstrate that LH-6 promoted the growth and development of immunodeficient mice in a concentration-dependent manner, remarkably elevated the immune organ index, and relieved the pathological characteristics of the spleen and thymus. Additional experiments also revealed that LH-6 effectively promoted the multiplication of splenic lymphocytes and natural killer activity, enhanced the function of abdominal macrophages, and apparently recovered delayed-type hypersensitivity in immunodeficient mice. The secretion of IgA, IgG, IgM, TNF-\u03b1, IL-1\u03b2, IL-6, and serum hemolysin were remarkably improved by LH-6, suggesting that LH-6 can synergistically strengthen cellular and humoral immunity. In addition, LH-6 promoted the phosphorylation of I\u03baB\u03b1 and nuclear translocation of p65, which correspondingly increased the phosphorylation levels of p38, JNK, and ERK; activated the NF-\u03baB and MAPK pathways; and exerted in vivo immunomodulatory activities. Docking results show that LH-6 has favorable binding energies to candidate proteins in the NF-\u03baB and MAPK pathways. To summarize, this research further demonstrated that LH-6 possesses in vivo immunomodulatory activity, which provides a possibility for the subsequent development of immune-enhancing functional foods.<\/jats:p>","DOI":"10.3390\/foods14111865","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:16:22Z","timestamp":1748204182000},"page":"1865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunoenhancement Function of the Novel Hexapeptide (LVVLGH) from Thick-Shelled Mussel (Mytilus coruscus) on Immunodeficient Mice by Activating the NF-\u03baB\/MAPK Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Xu","family":"Yang","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fandi","family":"Que","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqing","family":"Fu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4352-4264","authenticated-orcid":false,"given":"Fangmiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-9045","authenticated-orcid":false,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103408","DOI":"10.1016\/j.jff.2019.06.010","article-title":"Immunoenhancement effects of pentadecapeptide derived from Cyclina sinensis on immune-deficient mice induced by cyclophosphamide","volume":"60","author":"Yu","year":"2019","journal-title":"J. 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