{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:12:12Z","timestamp":1782234732333,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF), funded by the Ministry of Education","award":["RS-2024-00340898"],"award-info":[{"award-number":["RS-2024-00340898"]}]},{"name":"National Scholarship Fund of China","award":["CSC NO. 202409300002"],"award-info":[{"award-number":["CSC NO. 202409300002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Obesity-associated skeletal muscle atrophy is characterized by reduced muscle mass with excessive adipose accumulation, and there is no approved pharmacological therapy targeting both muscle anabolism and lipid metabolism. The root part of Ophiopogon japonicus (OJ), an edible traditional medicine (Liriopis seu Ophiopogonis Tuber), exhibits anti-diabetic, anti-inflammatory, and cardioprotective properties, yet its impact on obesity-associated muscle atrophy remains unknown. Methods: This study investigated the therapeutic potential and mechanisms of OJ extract against muscle atrophy in high-fat diet (HFD)-induced obesity mice and palmitate (PA)-stimulated C2C12 myotubes. Results: In obese mice, the administration of OJ extract inhibited muscle loss, improved muscle strength, and attenuated hepatic steatosis and dyslipidemia. Furthermore, OJ treatment restored myotube diameter, increased the expression of MyHC and Myogenin, and suppressed the expression of Atrogin-1 and MuRF1 in C2C12 myotubes. At the molecular level, OJ extract activated the PI3K-AKT-mTOR\/FoxO3a signaling pathway and reprogrammed lipid metabolism in gastrocnemius tissues and myotubes. Conclusions: OJ extract alleviates obesity-induced muscle atrophy through regulation of the PI3K-AKT-mTOR\/FoxO3a signaling pathway and lipid metabolism in muscle, indicating its potential as a natural therapeutic agent for obesity-associated muscle atrophy.<\/jats:p>","DOI":"10.3390\/nu17243946","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T13:42:52Z","timestamp":1765978972000},"page":"3946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ophiopogon japonicus Root Extract Attenuates Obesity-Induced Muscle Atrophy Through Regulation of the PI3K-AKT-mTOR\/FoxO3a Signaling Pathway and Lipid Metabolism in Mice and C2C12 Myotubes"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0998-9552","authenticated-orcid":false,"given":"Yang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6982-9277","authenticated-orcid":false,"given":"Haifeng","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenzi","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-9616","authenticated-orcid":false,"given":"Tran Khoa","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6113-1325","authenticated-orcid":false,"given":"In Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3623-5528","authenticated-orcid":false,"given":"Hyo Won","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Ki","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","first-page":"339","article-title":"Sarcopenic obesity and weight loss-induced muscle mass loss","volume":"28","author":"Caturano","year":"2025","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e243604","DOI":"10.1001\/jamanetworkopen.2024.3604","article-title":"Sarcopenia and Sarcopenic Obesity and Mortality Among Older People","volume":"7","author":"Benz","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jun, L., Robinson, M., Geetha, T., Broderick, T.L., and Babu, J.R. (2023). Prevalence and Mechanisms of Skeletal Muscle Atrophy in Metabolic Conditions. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032973"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1016\/j.clnu.2021.06.009","article-title":"Global prevalence of sarcopenic obesity in older adults: A systematic review and meta-analysis","volume":"40","author":"Gao","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Luo, Y., Wang, Y., Tang, S., Xu, L., Zhao, X., Han, M., Liu, Y., Xu, Y., and Han, B. (2024). Prevalence of sarcopenic obesity in the older non-hospitalized population: A systematic review and meta-analysis. BMC Geriatr., 24.","DOI":"10.1186\/s12877-024-04952-z"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, M., Tan, Y., Shi, Y., Wang, X., Liao, Z., and Wei, P. (2020). Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00568"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4093\/dmj.2023.0112","article-title":"Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies","volume":"47","author":"Mesinovic","year":"2023","journal-title":"Diabetes Metab. J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Feng, Y., Ren, Y., Zhang, X., Yang, S., Jiao, Q., Li, Q., and Jiang, W. (2024). Metabolites of traditional Chinese medicine targeting PI3K\/AKT signaling pathway for hypoglycemic effect in type 2 diabetes. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1373711"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mekonnen, Z., Petito, G., Shitaye, G., D\u2019Abrosca, G., Legesse, B.A., Addisu, S., Ragni, M., Lanni, A., Fattorusso, R., and Isernia, C. (2024). Insulin-Sensitizing Properties of Decoctions from Leaves, Stems, and Roots of Cucumis prophetarum L.. Molecules, 30.","DOI":"10.3390\/molecules30010098"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sknepnek, A., Miletic, D., Stupar, A., Salevic-Jelic, A., Nedovic, V., and Cvetanovic Kljakic, A. (2025). Natural solutions for diabetes: The therapeutic potential of plants and mushrooms. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1511049"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jep.2016.01.037","article-title":"Ophiopogon japonicus\u2014A phytochemical, ethnomedicinal and pharmacological review","volume":"181","author":"Chen","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","first-page":"16","article-title":"Phytochemical Screening, Characterization and Formulation and Evaluation of Herbal Gel of Abelmoschus Manihot for Atopic Dermatitis","volume":"9","author":"Chauhan","year":"2024","journal-title":"Int. J. Pharm. Qual. Assur."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhao, J.W., Chen, D.S., Deng, C.S., Wang, Q., Zhu, W., and Lin, L. (2017). Evaluation of anti-inflammatory activity of compounds isolated from the rhizome of Ophiopogon japonicas. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-016-1539-5"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Chen, B., Zhang, H., Zhang, J., and Xue, J. (2024). Extraction, purification, structural characterization, bioactivities, modifications and structure-activity relationship of polysaccharides from Ophiopogon japonicus: A review. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1484865"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ijbiomac.2020.01.068","article-title":"Cardioprotective effect of the polysaccharide from Ophiopogon japonicus on isoproterenol-induced myocardial ischemia in rats","volume":"147","author":"Fan","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, Z., Zhu, B., Peng, X., Li, S., and Zhao, J. (2022). Quality Evaluation of Ophiopogon japonicus from Two Authentic Geographical Origins in China Based on Physicochemical and Pharmacological Properties of Their Polysaccharides. Biomolecules, 12.","DOI":"10.3390\/biom12101491"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, J., Zhou, L., and Xiao, Z. (2025). Advances in the study of Ophiopogon japonicus polysaccharides: Structural characterization, bioactivity and gut microbiota modulation regulation. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1583711"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1097\/st9.0000000000000047","article-title":"Functional characterization of seven terpene synthases from Ophiopogon japonicus via engineered Escherichia coli","volume":"2","author":"Xu","year":"2024","journal-title":"Sci. Tradit. Chin. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.carbpol.2014.08.013","article-title":"MDG-1, a polysaccharide from Ophiopogon japonicus, prevents high fat diet-induced obesity and increases energy expenditure in mice","volume":"114","author":"Wang","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12573","DOI":"10.1074\/jbc.RA120.014357","article-title":"A polysaccharide extract from the medicinal plant Maidong inhibits the IKK-NF-kappaB pathway and IL-1beta-induced islet inflammation and increases insulin secretion","volume":"295","author":"Mao","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.ijbiomac.2011.06.026","article-title":"Hypoglycemic effects of MDG-1, a polysaccharide derived from Ophiopogon japonicas, in the ob\/ob mouse model of type 2 diabetes mellitus","volume":"49","author":"Xu","year":"2011","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/ajcn\/nqac031","article-title":"The energy balance model of obesity: Beyond calories in, calories out","volume":"115","author":"Hall","year":"2022","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chait, A., and den Hartigh, L.J. (2020). Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.00022"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1111\/obr.12862","article-title":"Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes","volume":"20","author":"Meex","year":"2019","journal-title":"Obes. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e002363","DOI":"10.1136\/bmjsem-2024-002363","article-title":"Effect of resistance exercise on body composition, muscle strength and cardiometabolic health during dietary weight loss in people living with overweight or obesity: A systematic review and meta-analysis","volume":"11","author":"Binmahfoz","year":"2025","journal-title":"BMJ Open Sport Exerc. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/bs.pmbts.2019.03.003","article-title":"The structures and biological functions of polysaccharides from traditional Chinese herbs","volume":"163","author":"Zeng","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"155639","DOI":"10.1016\/j.metabol.2023.155639","article-title":"Sarcopenic obesity: Emerging mechanisms and therapeutic potential","volume":"146","author":"Axelrod","year":"2023","journal-title":"Metabolism"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Greggi, C., Montanaro, M., Scioli, M.G., Puzzuoli, M., Gino Grillo, S., Scimeca, M., Mauriello, A., Orlandi, A., Gasbarra, E., and Iundusi, R. (2024). Modulation of Carnitine Palmitoyl Transferase 1b Expression and Activity in Muscle Pathophysiology in Osteoarthritis and Osteoporosis. Biomolecules, 14.","DOI":"10.3390\/biom14101289"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pang, X., Zhang, P., Chen, X., and Liu, W. (2023). Ubiquitin-proteasome pathway in skeletal muscle atrophy. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1289537"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Peris-Moreno, D., Taillandier, D., and Polge, C. (2020). MuRF1\/TRIM63, Master Regulator of Muscle Mass. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186663"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"738","DOI":"10.3390\/molecules14020738","article-title":"Ethanolic extract of propolis (EEP) enhances the apoptosis- inducing potential of TRAIL in cancer cells","volume":"14","author":"Szliszka","year":"2009","journal-title":"Molecules"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1016\/j.ajpath.2022.09.003","article-title":"Forkhead Box O Signaling Pathway in Skeletal Muscle Atrophy","volume":"192","author":"Chen","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1158\/1541-7786.MCR-15-0127","article-title":"FOXO3a and Posttranslational Modifications Mediate Glucocorticoid Sensitivity in B-ALL","volume":"13","author":"Consolaro","year":"2015","journal-title":"Mol. Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sirago, G., Picca, A., Calvani, R., Coelho-Junior, H.J., and Marzetti, E. (2022). Mammalian Target of Rapamycin (mTOR) Signaling at the Crossroad of Muscle Fiber Fate in Sarcopenia. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213823"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s11154-025-09954-9","article-title":"Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: Myocellular mechanisms involved","volume":"26","author":"Castillo","year":"2025","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Hu, Y., Pan, Y., Li, M., Niu, Y., Zhang, T., Sun, H., Zhou, S., Liu, M., and Zhang, Y. (2024). Fatty infiltration in the musculoskeletal system: Pathological mechanisms and clinical implications. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1406046"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"153877","DOI":"10.1016\/j.phymed.2021.153877","article-title":"Codonopsis lanceolata ameliorates sarcopenic obesity via recovering PI3K\/Akt pathway and lipid metabolism in skeletal muscle","volume":"96","author":"Han","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, P., and Weiskirchen, R. (2024). The Role of SCAP\/SREBP as Central Regulators of Lipid Metabolism in Hepatic Steatosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021109"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pollak, N., Janezic, E.G., Sink, Z., and Ugwoke, C.K. (2025). Crosstalk Between Skeletal Muscle and Proximal Connective Tissues in Lipid Dysregulation in Obesity and Type 2 Diabetes. Metabolites, 15.","DOI":"10.3390\/metabo15090581"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Mao, Z., and Zhang, W. (2018). Role of mTOR in Glucose and Lipid Metabolism. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072043"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-022-01073-0","article-title":"Trends in insulin resistance: Insights into mechanisms and therapeutic strategy","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/jcsm.13241","article-title":"Post-translational regulation of muscle growth, muscle aging and sarcopenia","volume":"14","author":"Zhong","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"32","DOI":"10.12703\/r\/11-32","article-title":"The role of mTORC1 in the regulation of skeletal muscle mass","volume":"11","author":"Bodine","year":"2022","journal-title":"Fac. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1096\/fj.201700741RR","article-title":"Ophiopogonin D alleviates high-fat diet-induced metabolic syndrome and changes the structure of gut microbiota in mice","volume":"32","author":"Chen","year":"2018","journal-title":"FASEB J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/aps.2016.14","article-title":"Methylophiopogonanone A suppresses ischemia\/reperfusion-induced myocardial apoptosis in mice via activating PI3K\/Akt\/eNOS signaling pathway","volume":"37","author":"He","year":"2016","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/24\/3946\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T05:21:31Z","timestamp":1766121691000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/24\/3946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":46,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["nu17243946"],"URL":"https:\/\/doi.org\/10.3390\/nu17243946","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]}}}