{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T20:08:00Z","timestamp":1768766880666,"version":"3.49.0"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1F1A1061577"],"award-info":[{"award-number":["NRF-2019R1F1A1061577"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Anemarrhenae rhizome and Phellodendri cortex have historically been used for the treatment of precocious puberty (PP) in oriental medicine. Our study aimed to evaluate the effect of APE, a mixture of the extracts from these herbs, against danazol-induced PP in female rats. The offspring were injected danazol to establish the PP model, and then treated with APE daily, and observed for vaginal opening. At the end of the study, the levels of gonadotropic hormones, such as estradiol, follicle-stimulating hormone, and luteinizing hormone, were determined by ELISA. Moreover, the mRNA expression of GnRH, netrin-1, and UNC5C in hypothalamic tissues was determined by real-time PCR. Network pharmacological analysis was performed to predict the active compounds of APE and their potential actions. APE treatment delayed vaginal opening in rats with PP. In addition, APE treatment reduced LH levels and suppressed UNC5C expression. Gene set enrichment analysis revealed that the targets of APE were significantly associated with GnRH signaling and ovarian steroidogenesis pathways. In conclusion, APE may be used as a therapeutic remedy to inhibit the activation of the hypothalamic\u2013pituitary\u2013gonadal axis.<\/jats:p>","DOI":"10.3390\/plants11010023","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T02:01:19Z","timestamp":1640224879000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Preventive Effect of Anemarrhenae rhizome and Phellodendri cortex on Danazol-Induced in Precocious Puberty in Female Rats and Network Pharmacological Analysis of Active Compounds"],"prefix":"10.3390","volume":"11","author":[{"given":"Kyeong Ri","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pediatrics, College of Korean Medicine, Daejeon University, Daejeon 300716, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuy An","family":"Trinh","sequence":"additional","affiliation":[{"name":"Saigon Pharmaceutical Science and Technology Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh 70000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-1028","authenticated-orcid":false,"given":"Ji Yun","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Food Science, Gyeongnam National University of Science and Technology, Jinju 52725, Korea"},{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dahae","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sehun","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, College of Medicine, Inje University, Busan 50834, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7125-7650","authenticated-orcid":false,"given":"Jonghyup","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, College of Medicine, Inje University, Busan 50834, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won-Yung","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-9148","authenticated-orcid":false,"given":"Chang-Eop","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki Sung","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Gachon University, Seongnam 13120, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7477-9991","authenticated-orcid":false,"given":"Hye Lim","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Korean Medicine, Daejeon University, Daejeon 300716, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2165\/00148581-200406040-00002","article-title":"Central precocious puberty: Current treatment options","volume":"6","year":"2004","journal-title":"Paediatr. Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/GCO.0000000000000099","article-title":"Precocious puberty","volume":"26","author":"Neely","year":"2014","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1542\/pir.36.7.319","article-title":"Precocious Puberty","volume":"36","author":"Long","year":"2015","journal-title":"Pediatr. Rev"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/humupd\/dmh012","article-title":"Precocious puberty and statural growth","volume":"10","author":"Carel","year":"2004","journal-title":"Hum. Reprod. Update"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jpeds.2018.12.022","article-title":"Incidence and Prevalence of Central Precocious Puberty in Korea: An Epidemiologic Study Based on a National Database","volume":"208","author":"Kim","year":"2019","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S2213-8587(15)00380-0","article-title":"Causes, diagnosis, and treatment of central precocious puberty","volume":"4","author":"Latronico","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1111\/cen.14410","article-title":"Long-term efficacy and safety of gonadotropin-releasing hormone analog treatment in children with idiopathic central precocious puberty: A systematic review and meta-analysis","volume":"94","author":"Luo","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1210\/jc.2013-1024","article-title":"Treatment and outcomes of precocious puberty: An update","volume":"98","author":"Fuqua","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s12098-013-1177-6","article-title":"Precocious puberty--perspectives on diagnosis and management","volume":"81","author":"Menon","year":"2014","journal-title":"Indian J. Pediatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R79","DOI":"10.1530\/EJE-15-0590","article-title":"MANAGEMENT OF ENDOCRINE DISEASE: Long-term outcomes of the treatment of central precocious puberty","volume":"174","author":"Guaraldi","year":"2016","journal-title":"Eur. J. Endocrinol."},{"key":"ref_11","unstructured":"Jin, H., Seo, G.Y., Jang, M.J., and Chae, Y.Y. (1996). Yagdalon, Iljung Publishing, Co."},{"key":"ref_12","unstructured":"Y.G., Y. (2006). New Dongui Medical Prescription, Chungdam Publishing, Co."},{"key":"ref_13","first-page":"1","article-title":"Applications of Prescriptions Including Anemarrhenae Rhizoma and Phellodendri Cortex in Dongeuibogam","volume":"19","author":"Sung","year":"2011","journal-title":"Herb. Formula Sci."},{"key":"ref_14","unstructured":"National Oriental Medical University Textbook Compilation Committee (2016). Herbalism, Yeonglim Publishing Co."},{"key":"ref_15","unstructured":"Department of Pediatrics, and University of Oriental Medicine (2020). Textbook of Pediatrics of Oriental Medicine, Uiseongdang Publishing Co."},{"key":"ref_16","first-page":"163","article-title":"The study for precocious puberty in recent journals of traditional Chinese medicine","volume":"22","author":"Lee","year":"2008","journal-title":"J. Pediatr. Korean Med."},{"key":"ref_17","first-page":"267","article-title":"Herbal medicine for idiopathic central precocious puberty: A protocol for a systematic review of controlled trials","volume":"97","author":"Lee","year":"2018","journal-title":"Medicine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0896-6273(90)90028-E","article-title":"Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis","volume":"5","author":"Mellon","year":"1990","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"191","DOI":"10.6065\/apem.2013.18.4.191","article-title":"The difference in serum alkaline phosphatase levels between girls with precocious puberty and those with normal puberty","volume":"18","author":"Jwa","year":"2013","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/S1995-7645(14)60322-9","article-title":"Expression and significance of netrin\u20131 and its receptor UNC5C in precocious puberty female rat hypothalamus","volume":"8","author":"Shang","year":"2015","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: A database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J. Cheminform."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jep.2017.05.006","article-title":"Characteristics of traditional Chinese medicine usage in children with precocious puberty: A nationwide population-based study","volume":"205","author":"Lin","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"596525","DOI":"10.3389\/fphar.2020.596525","article-title":"The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54\/GnRH in the Hypothalamus","volume":"11","author":"Bai","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5916168","DOI":"10.1155\/2020\/5916168","article-title":"The Therapeutic Effect of Shugan Xiehuo Formula in the Female Rat Model with Central Precocious Puberty","volume":"2020","author":"Yin","year":"2020","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jgr.2018.08.002","article-title":"Fermented ginseng extract, BST204, disturbs adipogenesis of mesenchymal stem cells through inhibition of S6 kinase 1 signaling","volume":"44","author":"Yi","year":"2020","journal-title":"J. Ginseng Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"191","DOI":"10.20307\/nps.2020.26.3.191","article-title":"Fucoidan induces apoptosis in A2058 cells through ROS-exposed activation of MAPKs signaling pathway","volume":"26","author":"Ryu","year":"2020","journal-title":"Nat. Prod. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"230","DOI":"10.20307\/nps.2020.26.3.230","article-title":"Anti-adipogenic pregnane steroid from a Hydractinia-associated fungus, Cladosporium sphaerospermum SW67","volume":"26","author":"Lee","year":"2020","journal-title":"Nat. Prod. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jgr.2020.02.005","article-title":"Ginsenosides Rk1 and Rg5 inhibit transforming growth factor-\u03b21-induced epithelial-mesenchymal transition and suppress migration, invasion, anoikis resistance, and development of stem-like features in lung cancer","volume":"45","author":"Kim","year":"2021","journal-title":"J. Ginseng Res."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/1\/23\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:08Z","timestamp":1760169068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/1\/23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["plants11010023"],"URL":"https:\/\/doi.org\/10.3390\/plants11010023","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]}}}