{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T14:19:28Z","timestamp":1772201968991,"version":"3.50.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Eleutheroside E (EE) is an anti-inflammatory natural compound derived from the edible medicinal herb <jats:italic>Acanthopanax senticosus<\/jats:italic>. This study aims to investigate the underlying mechanism of the anti-osteoporosis action of EE through network pharmacology, molecular docking and gut microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Network pharmacology was used to explore the potential core targets and main pathways mediated by EE in osteoporosis (OP) treatment. Molecular docking was exploited to investigate the interactions between the active anti-OP compounds in EE and the potential downstream targets. Following the multi-approach bioinformatics analysis, ovariectomy (OVX) model was also established to investigate the <jats:italic>in vivo<\/jats:italic> anti-OP effects of EE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The top 10 core targets in PPI network were TP53, AKT1, JUN, CTNNB1, STAT3, HIF1A, EP300, CREB1, IL1B and ESR1. Molecular docking results that the binding energy of target proteins and the active compounds was approximately between \u22125.0 and \u22127.0 kcal\/mol, which EE has the lowest docking binding energy with HIF1A. Enrichment analysis of GO and KEGG pathways of target proteins indicated that EE treatment could potentially alter numerous biological processes and cellular pathways. <jats:italic>In vivo<\/jats:italic> experiments demonstrated the protective effect of EE treatment against accelerated bone loss, where reduced serum levels of TRAP, CTX, TNF-\u03b1, LPS, and IL-6 and increased bone volume and serum levels of P1NP were observed in EE-treated mice. In addition, changes in gut microbiota were spotted by 16S rRNA gene sequencing, showing that EE treatment increased the relative abundance of <jats:italic>Lactobacillus<\/jats:italic> and decreased the relative abundance of <jats:italic>Clostridiaceae<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, these findings suggested that the characteristics of multi-target and multi-pathway of EE against OP. <jats:italic>In vivo<\/jats:italic>, EE prevents the onset of OP by regulating gut microbiota and inflammatory response and is therefore a potential OP drug.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1257298","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T16:22:59Z","timestamp":1699546979000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota"],"prefix":"10.3389","volume":"14","author":[{"given":"Tianyu","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Ge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youhong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qunwei","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-014-2940-x","article-title":"Incorporating bazedoxifene into the treatment paradigm for postmenopausal osteoporosis in Japan","volume":"26","author":"Ohta","year":"2015","journal-title":"Osteoporos Int"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-004-0018-y","article-title":"Postmenopausal osteoporosis","volume":"2","author":"Selby","year":"2004","journal-title":"Curr Osteoporos Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.17179\/excli2020-2591","article-title":"Osteoporosis: pathophysiology and therapeutic options","volume":"19","author":"Foger-Samwald","year":"2020","journal-title":"EXCLI J"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.26402\/jpp.2020.3.01","article-title":"Pharmacological agents and natural compounds: available treatments for osteoporosis","volume":"71","author":"Martiniakova","year":"2020","journal-title":"J Physiol Pharmacol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.392","article-title":"A novel RANKL-targeted flavonoid glycoside prevents osteoporosis through inhibiting NFATc1 and reactive oxygen species","volume":"11","author":"Hong","year":"2021","journal-title":"Clin Transl Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S139804","article-title":"Total flavonoids from Rhizoma Drynariae (Gusuibu) for treating osteoporotic fractures: implication in clinical practice","volume":"11","author":"Zhang","year":"2017","journal-title":"Drug Des Devel Ther"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.38.1763","article-title":"Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats","volume":"38","author":"Nishibe","year":"1990","journal-title":"Chem Pharm Bull"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0887-2333(03)00008-0","article-title":"Intraspecific relationship analysis by DNA markers and in vitro cytotoxic and antioxidant activity in Eleutherococcus senticosus","volume":"17","author":"Yu","year":"2003","journal-title":"Toxicol In Vitro"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.746","article-title":"The synthesis of Rantes, G-CSF, IL-4, IL-5, IL-6, IL-12 and IL-13 in human whole-blood cultures is modulated by an extract from Eleutherococcus senticosus L","volume":"15","author":"Schmolz","year":"2001","journal-title":"roots. 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