{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:03:27Z","timestamp":1792789407294,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Project of the Yunnan Province Agricultural Basic Research Joint Foundation","award":["202401BD070001-056"],"award-info":[{"award-number":["202401BD070001-056"]}]},{"name":"Project of the Yunnan Province Agricultural Basic Research Joint Foundation","award":["202403AK140041"],"award-info":[{"award-number":["202403AK140041"]}]},{"name":"Project of the Yunnan Province Agricultural Basic Research Joint Foundation","award":["202500043110184"],"award-info":[{"award-number":["202500043110184"]}]},{"name":"Project of Yunnan International Science and Technology Specialists","award":["202401BD070001-056"],"award-info":[{"award-number":["202401BD070001-056"]}]},{"name":"Project of Yunnan International Science and Technology Specialists","award":["202403AK140041"],"award-info":[{"award-number":["202403AK140041"]}]},{"name":"Project of Yunnan International Science and Technology Specialists","award":["202500043110184"],"award-info":[{"award-number":["202500043110184"]}]},{"name":"Development and Technical Services for Homology of Food and Medicine Project","award":["202401BD070001-056"],"award-info":[{"award-number":["202401BD070001-056"]}]},{"name":"Development and Technical Services for Homology of Food and Medicine Project","award":["202403AK140041"],"award-info":[{"award-number":["202403AK140041"]}]},{"name":"Development and Technical Services for Homology of Food and Medicine Project","award":["202500043110184"],"award-info":[{"award-number":["202500043110184"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>As one of the medicinal and edible resources, Gastrodia elata (GE) is considered to hold potential in alleviating alcoholic liver injury, yet its mechanism needs further elucidation. To explore the molecular mechanisms of GE against alcoholic liver injury, network pharmacology, molecular docking, molecular dynamics simulations, and cell experiments were employed. Thirty-two active components of GE may exert efficacy against alcohol-induced liver injury via regulating 207 targets. Among them, the main functional components might be 4-hydroxybenzyl methyl ether, 4-ethoxytolyl-4\u2032-hydroxybenzyl ether, pseudolaric acid B, palmitic acid, and myricetin. Analyses of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that a total of 322 GO items and 154 KEGG pathways are related to the effects of GE against alcoholic liver injury. The results of molecular docking show that the main active components of GE might interact with the key target proteins of GAPDH, PPARG, EGFR, STAT3, and AKT1. Molecular dynamics simulation further determined that pseudolaric acid B, as the core component, stably binds to these key target proteins. Cell experiments demonstrate that pseudolaric acid B exhibits a protective effect on ethanol-induced HepG2 cell injury by down-regulating the protein expression levels of GAPDH, STAT3, PPARG, and EGFR. Furthermore, the agent also suppresses IL-6 and inhibits the abnormal absorption of total cholesterol in HepG2 cells. Our findings suggest the efficacy and mechanism of GE in combating alcoholic liver injury and lay the groundwork for the precise development and utilization of GE.<\/jats:p>","DOI":"10.3390\/foods14122008","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T06:11:08Z","timestamp":1749190268000},"page":"2008","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Integrating Strategy of Network Pharmacology, Molecular Dynamics Simulation, and Experimental Verification to Investigate the Potential Mechanism of Gastrodia elata Against Alcoholic Liver Injury"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8677-7165","authenticated-orcid":false,"given":"Peiyuan","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Development and Utilization of Food and Medicinal Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China"},{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Development and Utilization of Food and Medicinal Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China"},{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0589-294X","authenticated-orcid":false,"given":"Xuanyou","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Development and Utilization of Food and Medicinal Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China"},{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengwang","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunfeng","family":"Ji","sequence":"additional","affiliation":[{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Peng","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Sheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Development and Utilization of Food and Medicinal Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Science, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lai, Y., Tan, Q., Xv, S., Huang, S., Wang, Y., Li, Y., Zeng, T., Mo, C., Chen, Y., and Huang, S. (2021). Ginsenoside Rb1 Alleviates Alcohol-Induced Liver Injury by Inhibiting Steatosis, Oxidative Stress, and Inflammation. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.616409"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.3748\/wjg.v25.i12.1445","article-title":"Growing burden of alcoholic liver disease in China: A review","volume":"25","author":"Wang","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, Y., Wang, S., Ni, H.M., Huang, H., and Ding, W.X. (2014). Autophagy in alcohol-induced multiorgan injury: Mechanisms and potential therapeutic targets. Biomed Res. Int., 2014.","DOI":"10.1155\/2014\/498491"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Duki\u0107, M., Radonji\u0107, T., Jovanovi\u0107, I., Zdravkovi\u0107, M., Todorovi\u0107, Z., Krai\u0161nik, N., Aran\u0111elovi\u0107, B., Mandi\u0107, O., Popadi\u0107, V., and Nikoli\u0107, N. (2023). Alcohol, Inflammation, and Microbiota in Alcoholic Liver Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043735"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jhep.2018.10.026","article-title":"Current trials and novel therapeutic targets for alcoholic hepatitis","volume":"70","author":"Singal","year":"2019","journal-title":"J. Hepatol"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, S., Yang, Y., Zhang, R., Gao, J., Wu, M., Wang, J., Sheng, J., and Sun, P. (2024). The Potential Mechanism of Alpiniae oxyphyllae Fructus Against Hyperuricemia: An Integration of Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation, and In Vitro Experiments. Nutrients, 17.","DOI":"10.3390\/nu17010071"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bildziukevich, U., \u00d6zdemir, Z., and Wimmer, Z. (2019). Recent Achievements in Medicinal and Supramolecular Chemistry of Betulinic Acid and Its Derivatives. Molecules, 24.","DOI":"10.3390\/molecules24193546"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yi, Z., Yue, Y., Kan, J., Wang, Z., Awad, S., Ibrahim, A., and Du, M. (2024). Biocontrol of Fusarium oxysporum-infested Gastrodia elata Bl. by Lactobacillus curvatus 2768-VOCs and mechanism of inhibition. Food Biosci., 62.","DOI":"10.1016\/j.fbio.2024.105174"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ahmad, O., Wang, B., Ma, K., Deng, Y., Li, M., Yang, L., Yang, Y., Zhao, J., Cheng, L., and Zhou, Q. (2019). Lipid Modulating Anti-oxidant Stress Activity of Gastrodin on Nonalcoholic Fatty Liver Disease Larval Zebrafish Model. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081984"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/ptr.5541","article-title":"Gastrodin Ameliorates Oxidative Stress and Proinflammatory Response in Nonalcoholic Fatty Liver Disease through the AMPK\/Nrf2 Pathway","volume":"30","author":"Qu","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tuo, Y., Lu, X., Tao, F., Tukhvatshin, M., Xiang, F., Wang, X., Shi, Y., Lin, J., and Hu, Y. (2024). The Potential Mechanisms of Catechins in Tea for Anti-Hypertension: An Integration of Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation. Foods, 13.","DOI":"10.3390\/foods13172685"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Challapa-Mamani, M.R., Tom\u00e1s-Alvarado, E., Espinoza-Baigorria, A., Le\u00f3n-Figueroa, D.A., Sah, R., Rodriguez-Morales, A.J., and Barboza, J.J. (2023). Molecular Docking and Molecular Dynamics Simulations in Related to Leishmania donovani: An Update and Literature Review. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8100457"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, J., Xian, J., Zhang, R., Wang, Z., Zhang, S., Zhao, D., Sheng, J., and Sun, P. (2025). \u03b1-Mangostin Exhibits Antitumor Activity Against NCI-H1975 Cells via the EGFR\/STAT3 Pathway: An Experimental and Molecular Simulation Study. Molecules, 30.","DOI":"10.3390\/molecules30061294"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.tibs.2019.06.004","article-title":"Bringing Molecular Dynamics Simulation Data into View","volume":"44","author":"Hildebrand","year":"2019","journal-title":"Trends. Biochem. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hou, W., Wei, B., and Liu, H.S. (2021). The Protective Effect of Panax notoginseng Mixture on Hepatic Ischemia\/Reperfusion Injury in Mice via Regulating NR3C2, SRC, and GAPDH. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.756259"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, D., Zhou, Q., Yang, X., Zhang, Z., Wang, D., Hu, D., Huang, Y., Sheng, J., and Wang, X. (2024). Gallic Acid Can Promote Low-Density Lipoprotein Uptake in HepG2 Cells via Increasing Low-Density Lipoprotein Receptor Accumulation. Molecules, 29.","DOI":"10.3390\/molecules29091999"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"148383","DOI":"10.1016\/j.gene.2024.148383","article-title":"Lianhua Qingwen exerts anti-liver cancer effects and synergistic efficacy with sorafenib through PI3K\/AKT pathway: Integrating network pharmacology, molecular docking, and experimental validation","volume":"912","author":"Wei","year":"2024","journal-title":"Gene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5606021","DOI":"10.1155\/2023\/5606021","article-title":"Gastrodia elata BI: A Comprehensive Review of Its Traditional Use, Botany, Phytochemistry, Pharmacology, and Pharmacokinetics","volume":"2023","author":"Wu","year":"2023","journal-title":"Evid-Based. Compl. Alt."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s10068-018-0374-5","article-title":"Protective effects of Gastrodia elata Blume on acetaminophen-induced liver and kidney toxicity in rats","volume":"27","author":"Seok","year":"2018","journal-title":"Food Sci. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, Y., Zhou, S., Rehman, M.U., Lin, F., Zhang, J., and Zhou, H. (2025). HTR1D regulates the PI3K\/Akt signaling pathway to impact hepatocellular carcinoma development and resistance to sorafenib. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-13575-5"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Park, W.Y., Song, G., Noh, J.H., Kim, T., Kim, J.J., Hong, S., Park, J., and Um, J.Y. (2021). Raphani Semen (Raphanus sativus L.) Ameliorates Alcoholic Fatty Liver Disease by Regulating De Novo Lipogenesis. Nutrients, 13.","DOI":"10.3390\/nu13124448"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13020-023-00759-z","article-title":"Exploring the effect of Yinzhihuang granules on alcoholic liver disease based on pharmacodynamics, network pharmacology and molecular docking","volume":"18","author":"Tan","year":"2023","journal-title":"Chin. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105032","DOI":"10.1016\/j.phrs.2020.105032","article-title":"S-allylmercaptocysteine inhibits mucin overexpression and inflammation via MAPKs and PI3K-Akt signaling pathways in acute respiratory distress syndrome","volume":"159","author":"An","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10959","DOI":"10.1038\/s41598-025-95563-0","article-title":"Global, regional, and national burdens of alcohol-related cirrhosis among women from 1992 to 2021 and its predictions","volume":"15","author":"Zhang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e005543","DOI":"10.1161\/JAHA.117.005543","article-title":"Coronary Atherosclerotic Vulnerable Plaque: Current Perspectives","volume":"6","author":"Stefanadis","year":"2017","journal-title":"J. Am. Heart. Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sun, P., Zhang, S., Qu, Y., Li, X., Chen, G., Wang, X., Sheng, J., and Wang, J. (2024). Coccinic acid exhibits anti-tumor efficacy against NSCLC harboring EGFR L858R\/T790M mutation via the EGFR\/STAT3 pathway. Bioorg. Chem., 154.","DOI":"10.1016\/j.bioorg.2024.108038"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.1039\/D2FO02701A","article-title":"Caffeine can alleviate non-alcoholic fatty liver disease by augmenting LDLR expression via targeting EGFR","volume":"14","author":"Huang","year":"2023","journal-title":"Food Funct."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, J., Wang, Y., Zhang, S., Qu, Y., Zhang, R., Wang, X., Sheng, J., and Sun, P. (2024). Inhibitory effect of 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone against NSCLC with L858R\/T790M\/C797S mutant EGFR. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-78146-3"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Reyes-Gordillo, K., Shah, R., Arellanes-Robledo, J., Cheng, Y., Ibrahim, J., and Tuma, P.L. (2019). Akt1 and Akt2 Isoforms Play Distinct Roles in Regulating the Development of Inflammation and Fibrosis Associated with Alcoholic Liver Disease. Cells, 8.","DOI":"10.3390\/cells8111337"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1053\/j.gastro.2008.01.016","article-title":"Cell type-dependent pro- and anti-inflammatory role of signal transducer and activator of transcription 3 in alcoholic liver injury","volume":"134","author":"Horiguchi","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Adamus, G. (2017). Impact of Autoantibodies against Glycolytic Enzymes on Pathogenicity of Autoimmune Retinopathy and Other Autoimmune Disorders. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00505"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113141","DOI":"10.1016\/j.ecoenv.2021.113141","article-title":"TNF-\u03b1\/TNFR1 regulates the polarization of Kupffer cells to mediate trichloroethylene-induced liver injury","volume":"230","author":"Zhang","year":"2022","journal-title":"Ecotox. Environ. Safe."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/nrc3818","article-title":"Revisiting STAT3 signalling in cancer: New and unexpected biological functions","volume":"14","author":"Yu","year":"2014","journal-title":"Nat. Rev. Cancer"}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/12\/2008\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:47:30Z","timestamp":1760032050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/12\/2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,6]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["foods14122008"],"URL":"https:\/\/doi.org\/10.3390\/foods14122008","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,6]]}}}