{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:08:28Z","timestamp":1779368908384,"version":"3.53.0"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2021A1515012067"],"award-info":[{"award-number":["2021A1515012067"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guangzhou City-University Joint Research Program","award":["2023A03J0046"],"award-info":[{"award-number":["2023A03J0046"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Lycium barbarum extracts have been shown to be effective in male reproductive protection and male infertility. However, its role in enhancing testicular function, such as testosterone synthesis, and the potential mechanism remain to be understood. To elucidate the effects of Lycium barbarum glycopeptide (LbGp) on testosterone synthesis, we isolated primary Leydig cells (LCs) from testes and performed RNA sequencing (RNA seq) on LCs treated with LbGp. In this study, we demonstrated that LbGp promoted testosterone synthesis in LCs both in vivo and in vitro. We also demonstrated that LbGp elevated adenosine 5\u2032-triphosphate (ATP) synthesis and cell proliferation by enhancing glucose metabolism. Mechanistically, LbGp upregulated testosterone synthesis by suppressing TGF-\u03b2 pathway and enhancing the expression of steroidogenic genes: Cyp11a1, Hsd3b1, Hsd17b3, Star, and Sf-1. These findings indicate that LbGp plays an important role in enhancing testicular function and promoting testosterone synthesis.<\/jats:p>","DOI":"10.3390\/biom15030425","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:49:57Z","timestamp":1742197797000},"page":"425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Lycium barbarum Glycopeptide Promotes Testosterone Synthesis and Glucose Metabolism in Leydig Cells of the Testis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9916-4475","authenticated-orcid":false,"given":"Jinlian","family":"Liang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianchan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Jinan University, Guangzhou 510632, China"},{"name":"Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinrong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital of Jinan University, Guangzhou 510632, China"},{"name":"Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok","family":"So","sequence":"additional","affiliation":[{"name":"Institute of Clinical Research for Mental Health, The First Affiliated Hospital Jinan University, Guangzhou 510632, China"},{"name":"Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay Area, Guangzhou 510515, China"},{"name":"State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2401-6168","authenticated-orcid":false,"given":"Guobing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4276-9251","authenticated-orcid":false,"given":"Yuan-Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Guangzhou University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/0010-7824(75)90111-0","article-title":"Leydig cells","volume":"11","author":"Neaves","year":"1975","journal-title":"Contraception"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1007\/s00018-019-03101-9","article-title":"The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis","volume":"76","author":"Zhou","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1210\/endo-124-3-1217","article-title":"Restoration of advanced spermatogenic cells in the experimentally regressed rat testis: Quantitative relationship to testosterone concentration within the testis","volume":"124","author":"Awoniyi","year":"1989","journal-title":"Endocrinology"},{"key":"ref_4","first-page":"103","article-title":"Roles of age and androgen in the regulation of sex accessory organs","volume":"3","author":"Fujii","year":"1977","journal-title":"Adv. Sex. Horm. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e12901","DOI":"10.1111\/ijcp.12901","article-title":"UK policy statements on testosterone deficiency","volume":"71","author":"Hackett","year":"2017","journal-title":"Int. J. Clin. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1210\/jc.2018-00229","article-title":"Testosterone Therapy in Men with Hypogonadism: An Endocrine Society Clinical Practice Guideline","volume":"103","author":"Bhasin","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"508","DOI":"10.5534\/wjmh.221027","article-title":"The British Society for Sexual Medicine Guidelines on Male Adult Testosterone Deficiency, with Statements for Practice","volume":"41","author":"Hackett","year":"2023","journal-title":"World J. Mens. Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/andr.274","article-title":"Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men","volume":"2","author":"Zarotsky","year":"2014","journal-title":"Andrology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1001\/jama.295.11.1288","article-title":"Sex differences of endogenous sex hormones and risk of type 2 diabetes: A systematic review and meta-analysis","volume":"295","author":"Ding","year":"2006","journal-title":"Jama"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/andr.13367","article-title":"Testosterone therapy in diabetes and pre-diabetes","volume":"11","author":"Corona","year":"2023","journal-title":"Andrology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1056\/NEJMoa2215025","article-title":"Cardiovascular Safety of Testosterone-Replacement Therapy","volume":"389","author":"Lincoff","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1056\/NEJMc1009326","article-title":"Adverse events associated with testosterone administration","volume":"363","author":"Khoo","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1001\/jama.2013.280386","article-title":"Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels","volume":"310","author":"Vigen","year":"2013","journal-title":"Jama"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.metabol.2018.03.007","article-title":"Testosterone replacement therapy: For whom, when and how?","volume":"86","author":"Tsametis","year":"2018","journal-title":"Metabolism"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shehab, N.G., Omolaoye, T.S., Du Plessis, S.S., Rawat, S.S., Naidoo, N., Abushawish, K.Y., Ahmed, A., Alaa, B., Ihsan, H., and Abdelhalim, M. (2024). Phytochemical Evaluation of Lepidium meyenii, Trigonella foenum-graecum, Spirulina platensis, and Tribulus arabica, and Their Potential Effect on Monosodium Glutamate Induced Male Reproductive Dysfunction in Adult Wistar Rats. Antioxidants, 13.","DOI":"10.3390\/antiox13080939"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1002\/ptr.3360","article-title":"Physiological aspects of male libido enhanced by standardized Trigonella foenum-graecum extract and mineral formulation","volume":"25","author":"Steels","year":"2011","journal-title":"Phytother. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e14014","DOI":"10.1111\/and.14014","article-title":"In vitro and in vivo investigation of the therapeutic mechanism of Lycium Chinense and Cuscutae Semen on oligoasthenozoospermia","volume":"53","author":"Wang","year":"2021","journal-title":"Andrologia"},{"key":"ref_18","first-page":"512","article-title":"Isolation, purification and physico-chemical properties of immunoactive constituents from the fruit of Lycium barbarum L.","volume":"33","author":"Huang","year":"1998","journal-title":"Yao Xue Xue Bao"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1186\/s12967-023-04648-9","article-title":"Lycium barbarum glycopeptide alleviates neuroinflammation in spinal cord injury via modulating docosahexaenoic acid to inhibiting MAPKs\/NF-kB and pyroptosis pathways","volume":"21","author":"Jiang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"154864","DOI":"10.1016\/j.phymed.2023.154864","article-title":"Lycium barbarum (Wolfberry) glycopeptide prevents stress-induced anxiety disorders by regulating oxidative stress and ferroptosis in the medial prefrontal cortex","volume":"116","author":"Dai","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"156275","DOI":"10.1016\/j.phymed.2024.156275","article-title":"Wolfberry (Lycium barbarum) glycopeptide attenuates dopaminergic neurons loss by inhibiting lipid peroxidation in Parkinson\u2019s disease","volume":"136","author":"Lin","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1038\/s41417-023-00611-4","article-title":"Lycium barbarum glycopeptide targets PER2 to inhibit lipogenesis in glioblastoma by downregulating SREBP1c","volume":"30","author":"Yao","year":"2023","journal-title":"Cancer Gene Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"43","DOI":"10.5534\/wjmh.2017.35.1.43","article-title":"Administration of Goji (Lycium chinense Mill.) Extracts Improves Erectile Function in Old Aged Rat Model","volume":"35","author":"Moon","year":"2017","journal-title":"World J. Mens. Health"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1507\/endocrj.EJ16-0430","article-title":"Protective effects of Lycium barbarum polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice","volume":"64","author":"Shi","year":"2017","journal-title":"Endocr. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s12192-022-01266-0","article-title":"Effects of Lycium barbarum glycopeptide on renal and testicular injury induced by di(2-ethylhexyl) phthalate","volume":"27","author":"Zhou","year":"2022","journal-title":"Cell Stress. Chaperones"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Liang, J., Tang, Y., Li, H., Mei, J., Cao, Z., Xia, H., Huang, R., Yang, Y., and Huang, Y. (2021). Isolation of Primary Leydig Cells from Murine Testis. Bio Protoc., 11.","DOI":"10.21769\/BioProtoc.4223"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Galano, M., Li, Y., Li, L., Sottas, C., and Papadopoulos, V. (2021). Role of Constitutive STAR in Leydig Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042021"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.rbmo.2015.07.009","article-title":"Inhibitory effect of melatonin on testosterone synthesis is mediated via GATA-4\/SF-1 transcription factors","volume":"31","author":"Qin","year":"2015","journal-title":"Reprod. Biomed. Online"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Park, E., Song, C.H., Park, J.I., Ahn, R.S., Choi, H.S., Ko, C., and Lee, K. (2014). Transforming growth factor-\u03b21 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104812"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1530\/REP-16-0044","article-title":"TGFB1 represses the expression of SF1 and LRH1 to inhibit E(2) production in rat LCs","volume":"153","author":"Yang","year":"2017","journal-title":"Reproduction"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1093\/biolre\/ioad025","article-title":"TGF-\u03b21 induced activations of Smad2 and miRNAs inhibit SF-1- and LRH-1-dependent CYP19 expression in rat Leydig cells\u2020","volume":"108","author":"Ma","year":"2023","journal-title":"Biol. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/ptr.3633","article-title":"Protective effect of Lycium barbarum polysaccharides against doxorubicin-induced testicular toxicity in rats","volume":"26","author":"Xin","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s00441-018-2891-1","article-title":"Lycium barbarum polysaccharide attenuates diabetic testicular dysfunction via inhibition of the PI3K\/Akt pathway-mediated abnormal autophagy in male mice","volume":"374","author":"Shi","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1530\/REP-10-0098","article-title":"Interference RNA-based silencing of endogenous SMAD4 in porcine granulosa cells resulted in decreased FSH-mediated granulosa cells proliferation and steroidogenesis","volume":"141","author":"Wang","year":"2011","journal-title":"Reproduction"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1071\/RD20325","article-title":"Transforming growth factor-\u03b21 disrupts angiogenesis during the follicular-luteal transition through the Smad-serpin family E member 1 (SERPINE1)\/serpin family B member 5 (SERPINB5) signalling pathway in the cow","volume":"33","author":"Yan","year":"2021","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1530\/REP-19-0311","article-title":"Modulatory effects of TGF-\u03b21 and BMP6 on thecal angiogenesis and steroidogenesis in the bovine ovary","volume":"159","author":"Mattar","year":"2020","journal-title":"Reproduction"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.cyto.2018.03.038","article-title":"TGFB1 modulates in vitro secretory activity and viability of equine luteal cells","volume":"110","author":"Wolodko","year":"2018","journal-title":"Cytokine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.mce.2016.07.026","article-title":"Endogenous inhibins regulate steroidogenesis in mouse TM3 Leydig cells by altering SMAD2 signalling","volume":"436","author":"Wang","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1186\/s13046-020-01765-x","article-title":"Glycometabolic rearrangements--aerobic glycolysis in pancreatic cancer: Causes, characteristics and clinical applications","volume":"39","author":"Cao","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/s41419-022-05213-w","article-title":"FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis","volume":"13","author":"Cai","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.15252\/embj.201490379","article-title":"Aerobic glycolysis tunes YAP\/TAZ transcriptional activity","volume":"34","author":"Enzo","year":"2015","journal-title":"Embo J."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/425\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:45:11Z","timestamp":1779367511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/3\/425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["biom15030425"],"URL":"https:\/\/doi.org\/10.3390\/biom15030425","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]}}}