{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:42:53Z","timestamp":1788846173199,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T00:00:00Z","timestamp":1720828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin Provincial Development and Reform Commission","award":["2023C038-3"],"award-info":[{"award-number":["2023C038-3"]}]},{"name":"Jilin Provincial Development and Reform Commission","award":["20210202030NC"],"award-info":[{"award-number":["20210202030NC"]}]},{"name":"Jilin Province Science and Technology Development Plan Project","award":["2023C038-3"],"award-info":[{"award-number":["2023C038-3"]}]},{"name":"Jilin Province Science and Technology Development Plan Project","award":["20210202030NC"],"award-info":[{"award-number":["20210202030NC"]}]},{"name":"Jilin Province Innovative and Entrepreneurial Talent Funding Project","award":["2023C038-3"],"award-info":[{"award-number":["2023C038-3"]}]},{"name":"Jilin Province Innovative and Entrepreneurial Talent Funding Project","award":["20210202030NC"],"award-info":[{"award-number":["20210202030NC"]}]},{"name":"Chinese Academy of Sciences Pioneer Hundred Talents Program","award":["2023C038-3"],"award-info":[{"award-number":["2023C038-3"]}]},{"name":"Chinese Academy of Sciences Pioneer Hundred Talents Program","award":["20210202030NC"],"award-info":[{"award-number":["20210202030NC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Velvet antler, a traditional tonic widely used in East Asia for its health benefits, is explored in this study for its protective effects against hypoxia-induced damage using Caenorhabditis elegans (C. elegans) as a model. Hypoxia, characterized by low oxygen availability, induces significant physiological stress and potential tissue damage. Our research demonstrates that methanol extracts from velvet antler (MEs) enhance the survival of C. elegans under hypoxic conditions. This enhancement is achieved through the stabilization of hypoxia-inducible factor-1 (HIF-1) and the promotion of lipid accumulation, both of which are crucial for mitigating cellular damage. Specifically, MEs improve mitochondrial function, increase ATP production, and aid in the recovery of physical activity in C. elegans post-hypoxia or following hypoxia\u2013reoxygenation (HR). The pivotal role of HIF-1 is underscored by the loss of these protective effects when HIF-1 function is inhibited. Additionally, our findings reveal that the gene related to lipid metabolism, ech-8, significantly contributes to the lipid accumulation that enhances resilience to hypoxia in C. elegans treated with MEs. These results not only highlight the therapeutic potential of velvet antler in modern medical applications, particularly for conditions involving hypoxic stress, but also provide insights into the molecular mechanisms by which MEs confer protection against hypoxic damage.<\/jats:p>","DOI":"10.3390\/nu16142257","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T08:35:17Z","timestamp":1721032517000},"page":"2257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Protective Effects of Velvet Antler Methanol Extracts on Hypoxia-Induced Damage in Caenorhabditis elegans through HIF-1 and ECH-8 Mediated Lipid Accumulation"],"prefix":"10.3390","volume":"16","author":[{"given":"Ru","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3415-5612","authenticated-orcid":false,"given":"Xiaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China"},{"name":"School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0835-8317","authenticated-orcid":false,"given":"Yinghua","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun 130112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41580-020-0227-y","article-title":"Cellular adaptation to hypoxia through hypoxia inducible factors and beyond","volume":"21","author":"Lee","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41467-020-14469-9","article-title":"Cellular adaptation to oxygen deficiency beyond the Nobel award","volume":"11","author":"Simon","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1164\/rccm.202006-2467OC","article-title":"Hypoxia Increases the Potential for Neutrophil-mediated Endothelial Damage in Chronic Obstructive Pulmonary Disease","volume":"205","author":"Lodge","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41584-021-00621-2","article-title":"The role of HIF proteins in maintaining the metabolic health of the intervertebral disc","volume":"17","author":"Silagi","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00424-022-02683-x","article-title":"Lipid metabolic reprogramming by hypoxia-inducible factor-1 in the hypoxic tumour microenvironment","volume":"474","author":"Seo","year":"2022","journal-title":"Pfl\u00fcgers Arch. Eur. J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5413","DOI":"10.1111\/febs.16110","article-title":"Regulation of redox signaling in HIF-1-dependent tumor angiogenesis","volume":"289","author":"Manuelli","year":"2022","journal-title":"FEBS J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"108186","DOI":"10.1016\/j.pharmthera.2022.108186","article-title":"The role of hypoxia-inducible factors in cardiovascular diseases","volume":"238","author":"Yu","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1002\/med.21771","article-title":"The role of hypoxia-inducible factor 1 in tumor immune evasion","volume":"41","author":"You","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s43587-021-00054-2","article-title":"Hypoxia compromises the mitochondrial metabolism of Alzheimer\u2019s disease microglia via HIF1","volume":"1","author":"Luis","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41421-021-00361-3","article-title":"Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor","volume":"8","author":"Liu","year":"2022","journal-title":"Cell Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8864395","DOI":"10.1155\/2021\/8864395","article-title":"Velvet Antler Methanol Extracts Ameliorate Parkinson\u2019s Disease by Inhibiting Oxidative Stress and Neuroinflammation: From C. elegans to Mice","volume":"2021","author":"Liu","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, X., Li, H., Liu, Y., Wu, H., Wang, H., Jin, S., Lu, Y., Chang, S., Liu, R., and Peng, Y. (2020). Velvet antler methanol extracts (MEs) protects against oxidative stress in Caenorhabditis elegans by SKN-1. Biomed. Pharmacother., 121.","DOI":"10.1016\/j.biopha.2019.109668"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6168","DOI":"10.1038\/s41467-022-33849-x","article-title":"The hypoxia response pathway promotes PEP carboxykinase and gluconeogenesis in C. elegans","volume":"13","author":"Vora","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22642","DOI":"10.1074\/jbc.272.36.22642","article-title":"Hypoxia-inducible Factor 1\u03b1 (HIF-1\u03b1) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions. Its stabilization by hypoxia depends on redox-induced changes","volume":"272","author":"Salceda","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41429-021-00451-0","article-title":"Targeting hypoxia-inducible factor 1 (HIF-1) signaling with natural products toward cancer chemotherapy","volume":"74","author":"Ikeda","year":"2021","journal-title":"J. Antibiot."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41431-022-01260-1","article-title":"Improving diagnosis of mitochondrial fatty-acid oxidation disorders","volume":"31","author":"Fouilhoux","year":"2023","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Spanier, B., Lasch, K., Marsch, S., Benner, J., Liao, W., Hu, H., Kienberger, H., Eisenreich, W., and Daniel, H. (2009). How the Intestinal Peptide Transporter PEPT-1 Contributes to an Obesity Phenotype in Caenorhabditits elegans. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006279"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2101077","DOI":"10.1002\/mnfr.202101077","article-title":"S-Allylcysteine Ameliorates Aging Features via Regulating Mitochondrial Dynamics in Naturally Aged C57BL\/6J Mice","volume":"66","author":"Chen","year":"2022","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/s42255-022-00593-x","article-title":"Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel\u2013Lindau syndrome","volume":"4","author":"Li","year":"2022","journal-title":"Nat. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1002\/med.22034","article-title":"Enhancing healthy aging with small molecules: A mitochondrial perspective","volume":"44","author":"Qin","year":"2024","journal-title":"Med. Res. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/nn.2152","article-title":"Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans","volume":"11","author":"Pocock","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e67911","DOI":"10.7554\/eLife.67911","article-title":"Nuclear hormone receptor NHR-49 acts in parallel with HIF-1 to promote hypoxia adaptation in Caenorhabditis elegans","volume":"11","author":"Doering","year":"2022","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1749-6632.2003.tb03222.x","article-title":"Genetic Analysis of Hypoxia Signaling and Response in C. elegans","volume":"995","author":"Shen","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00109-023-02308-5","article-title":"The role of hypoxia-inducible factor 1\u03b1 in hepatic lipid metabolism","volume":"101","author":"Luo","year":"2023","journal-title":"J. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101168","DOI":"10.1016\/j.molmet.2021.101168","article-title":"Hypoxia-inducible lipid droplet-associated induces DGAT1 and promotes lipid storage in hepatocytes","volume":"47","author":"Rodriguez","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"baaa037","DOI":"10.1093\/database\/baaa037","article-title":"Automated generation of gene summaries at the Alliance of Genome Resources","volume":"2020","author":"Kishore","year":"2020","journal-title":"Database"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1007\/s11427-021-2016-9","article-title":"Endocrine pheromones couple fat rationing to dauer diapause through HNF4\u03b1 nuclear receptors","volume":"64","author":"Gao","year":"2021","journal-title":"Sci. China Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, Y., Li, C., Zhang, J., Xu, X., Fu, L., Xu, J., Zhu, H., Hu, Y., Li, C., and Wang, M. (2022). Polyunsaturated fatty acids promote the rapid fusion of lipid droplets in Caenorhabditis elegans. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.102179"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pei, H., Du, R., He, Z., Yang, Y., Wu, S., Li, W., Sheng, J., Lv, Y., and Han, C. (2023). Protection of a novel velvet antler polypeptide PNP1 against cerebral ischemia-reperfusion injury. Int. J. Biol. Macromol., 247.","DOI":"10.1016\/j.ijbiomac.2023.125815"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1142\/S0192415X22500689","article-title":"Deer Velvet Antler Extracts Exert Anti-Inflammatory and Anti-Arthritic Effects on Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Distinct Mouse Arthritis","volume":"50","author":"Cheng","year":"2022","journal-title":"Am. J. Chin. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1038\/s41418-021-00741-y","article-title":"Metabolic adaptation to hypoxia: Do worms and cancer cells share common metabolic responses to hypoxic stress?","volume":"28","author":"Baumeister","year":"2021","journal-title":"Cell Death Differ"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tig.2013.01.010","article-title":"Worms under stress: C. elegans stress response and its relevance to complex human disease and aging","volume":"29","author":"Rodriguez","year":"2013","journal-title":"Trends Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.celrep.2014.08.056","article-title":"Fatty Acid Uptake and Lipid Storage Induced by HIF-1\u03b1 Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation","volume":"9","author":"Bensaad","year":"2014","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e00390-18","DOI":"10.1128\/MCB.00390-18","article-title":"Hypoxia Restrains Lipid Utilization via Protein Kinase A and Adipose Triglyceride Lipase Downregulation through Hypoxia-Inducible Factor","volume":"39","author":"Han","year":"2019","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1038\/s41467-020-18369-w","article-title":"PQM-1 controls hypoxic survival via regulation of lipid metabolism","volume":"11","author":"Heimbucher","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Danielli, M., Perne, L., Jovi\u010di\u0107, E.J., and Petan, T. (2023). Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1104725"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/14\/2257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:16:15Z","timestamp":1760109375000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/14\/2257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,13]]},"references-count":36,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["nu16142257"],"URL":"https:\/\/doi.org\/10.3390\/nu16142257","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,13]]}}}