{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:01:35Z","timestamp":1790776895590,"version":"4.1.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Huangtcia renifolia<\/jats:italic>\n                      (L.) H. Ohashi &amp;amp; K. Ohashi, a traditional folk medicine, has been used for centuries by the Dai people in Xishuangbanna, Yunnan Province, China. Traditionally, it has been used to clear kidney heat, promote diuresis, and treat conditions, including kidney deficiency, sexual dysfunction, hepatitis, and osteoporosis. Recent pharmacological investigations indicate that\n                      <jats:italic>Huangtcia renifolia<\/jats:italic>\n                      ethanol extract (DRS) exerts bone-protective effects, partially via modulation of OPG\/RANKL\/RANK and BMP-2\/Smad signaling pathways. This study used an integrated multi-omics strategy to explore the bone-protective effects of DRS and its potential mechanisms in ovariectomized (OVX) rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The chemical composition of DRS was profiled by widely targeted UPLC-MS\/MS. Osteoporosis was induced in rats via bilateral ovariectomy, and bone status was assessed using serum biochemical analyses, micro-computed tomography (microCT) and hematoxylin-eosin (H&amp;amp;E) staining of femur tissue. Integrated multi-omics analyses were subsequently performed, comprising 16S rRNA sequencing of fecal microbiota, widely targeted serum metabolomics, and femoral transcriptomic sequencing.\n                      <jats:italic>In vitro<\/jats:italic>\n                      validation was performed using MC3T3-E1 osteoblasts treated with DRS-containing serum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DRS treatment significantly increased bone mineral density, improved trabecular bone microstructure, and effectively reversed abnormal bone turnover markers in OVX rats. Gut microbiota profiling indicated that DRS treatment modulated the gut microbiota, with significant increases in the relative abundance of\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      and\n                      <jats:italic>Limosilactobacillus<\/jats:italic>\n                      . Serum metabolomics identified 34 metabolites differentially abundant in DRS-treated rats, with pathway enrichment analyses highlighting purine metabolism as one of the principal affected pathways. Femoral transcriptomics and RT-qPCR validation indicated that DRS treatment was associated with upregulation of osteogenic genes (\n                      <jats:italic>Col1a1<\/jats:italic>\n                      and\n                      <jats:italic>Col1a2<\/jats:italic>\n                      ) and downregulation of muscle-related genes (\n                      <jats:italic>Myog<\/jats:italic>\n                      ,\n                      <jats:italic>Myh3<\/jats:italic>\n                      , and\n                      <jats:italic>Mstn<\/jats:italic>\n                      ), consistent with potential modulation of pathways linking bone and muscle function. Additionally, DRS-containing serum dose-dependently enhanced osteoblast differentiation and upregulated BMP2 and RUNX2 expression\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DRS treatment protects against osteoporosis in OVX rats. This protection was associated with gut microbiota composition, serum metabolic profiles, and the expression balance between osteogenic and muscle-related genes in bone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1795581","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:38:15Z","timestamp":1790775495000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics analysis explores the potential mechanisms of Huangtcia renifolia ethanolic extract against osteoporosis in ovariectomized rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Liping","family":"Yang","sequence":"first","affiliation":[{"name":"Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Duan","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Dai and Yi Medicines, Yunnan University of Chinese Medicine","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1602599","article-title":"Postmenopausal osteoporosis","volume":"374","author":"Black","year":"2016","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117285","article-title":"Ulmus macrocarpa Hance trunk bark extracts inhibit Rankl-induced osteoclast differentiation and prevent ovariectomy-induced osteoporosis in mice","volume":"319","author":"Jeong","year":"2024","journal-title":"J Ethnopharmacol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.21106","article-title":"Prevalence of osteoporosis and fracture in China: The China osteoporosis prevalence study","volume":"4","author":"Wang","year":"2021","journal-title":"JAMA Netw Open"},{"key":"B4","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1080\/13697137.2021.1951206","article-title":"Osteoporosis and fractures in women: The burden of disease","volume":"25","author":"Lorentzon","year":"2022","journal-title":"Climacteric"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15024","article-title":"Overview of treatment approaches to osteoporosis","volume":"178","author":"Langdahl","year":"2021","journal-title":"Br J Pharmacol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","article-title":"Osteoporosis treatment: Recent developments and ongoing challenges","volume":"5","author":"Khosla","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3928\/01477447-20220719-03","article-title":"Osteoporosis: An update on screening, diagnosis, evaluation, and treatment","volume":"46","author":"Sabri","year":"2023","journal-title":"Orthopedics"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100451R","article-title":"Gut microbiota and bone metabolism","volume":"35","author":"Lu","year":"2021","journal-title":"FASEB J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41522-022-00348-2","article-title":"One-year supplementation with Lactobacillus reuteri Atcc Pta 6475 counteracts a degradation of gut microbiota in older women with low bone mineral density","volume":"8","author":"Li","year":"2022","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B10","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1159\/000541999","article-title":"Gut microbiota-bone axis","volume":"81","author":"Indrio","year":"2025","journal-title":"Ann Nutr Metab"},{"key":"B11","doi-asserted-by":"publisher","first-page":"5747","DOI":"10.1038\/s41598-017-06126-x","article-title":"Commensal gut microbiota immunomodulatory actions in bone marrow and liver have catabolic effects on skeletal homeostasis in health","volume":"7","author":"Novince","year":"2017","journal-title":"Sci Rep"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.3390\/molecules23071517","article-title":"Commensal microbiota enhance both osteoclast and osteoblast activities","volume":"23","author":"Uchida","year":"2018","journal-title":"Molecules"},{"key":"B13","doi-asserted-by":"publisher","first-page":"a031203","DOI":"10.1101\/cshperspect.a031203","article-title":"Bone remodeling and the microbiome","volume":"8","author":"Pacifici","year":"2018","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.11842\/wst.20220907002","article-title":"The therapeutic effect of Desmodium renifolium on chronic renal failure","volume":"25","author":"Xiao","year":"2023","journal-title":"Modernization Traditional Chin Med Materia Medica-World Sci Technol"},{"key":"B15","article-title":"Effects of Dai medicine Huangtcia renifolia on sexual behavior and sex hormones in male rats","volume":"58","author":"Yang","year":"2022","journal-title":"Chin J Vet Med"},{"key":"B16","volume-title":"Study on the chemical constituents from stems of Desmodium renifolium (Linn.) Schindl","author":"Yang","year":"2015"},{"key":"B17","volume-title":"Studies on anti-osteoporotic constituents from Podocarpium podocarpum and their mechanisms","author":"Ma","year":"2013"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.11842\/wst.20230526002","article-title":"Anti-osteoporosis effect of Desmodium renifolium (Linn.) Schindl based on Opg\/Rankl\/Rank pathway","volume":"26","author":"Yang","year":"2024","journal-title":"Modernization Traditional Chin Med Materia Medica-World Sci Technol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20220714.402","article-title":"Effect of Desmodium renifolium on ovariectomized rat model of osteoporosis via Bmp-2\/ Smads signaling pathway","volume":"47","author":"Duan","year":"2022","journal-title":"China J Chin Materia Med"},{"key":"B20","volume-title":"Application of Huangtcia renifolia and its extracts in preparing drugs for treating sarcopenia","author":"Duan","year":"2023"},{"key":"B21","article-title":"The laboratory rat as an animal model for osteoporosis research","volume":"58","author":"Lelovas","year":"2008","journal-title":"Comp Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0169-6009(91)90124-i","article-title":"The ovariectomized rat model of postmenopausal bone loss","volume":"15","author":"Kalu","year":"1991","journal-title":"Bone Miner"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.799053","article-title":"Lactobacillus paracasei Bd5115-derived 2-hydroxy-3-methylbutyric acid promotes intestinal epithelial cells proliferation by upregulating the Myc signaling pathway","volume":"9","author":"Qiao","year":"2022","journal-title":"Front Nutr"},{"key":"B24","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1080\/13880209.2022.2056208","article-title":"Gut microbiota and metabonomics used to explore the mechanism of Qing'e pills in alleviating osteoporosis","volume":"60","author":"Xie","year":"2022","journal-title":"Pharm Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23471","article-title":"The role of Bacillus acidophilus in osteoporosis and its roles in proliferation and differentiation","volume":"34","author":"Chen","year":"2020","journal-title":"J Clin Lab Anal"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113784","article-title":"Purine metabolism in the development of osteoporosis","volume":"155","author":"Yang","year":"2022","journal-title":"BioMed Pharmacother"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1795581\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:38:21Z","timestamp":1790775501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1795581\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":26,"alternative-id":["10.3389\/fendo.2026.1795581"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1795581","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1795581"}}