{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:47:18Z","timestamp":1790286438613,"version":"4.1.0"},"reference-count":232,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["(BK20241040)"],"award-info":[{"award-number":["(BK20241040)"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Fund for Colleges and Universities in Jiangsu Province","award":["(1020241241)"],"award-info":[{"award-number":["(1020241241)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Icariin (ICA), a prenylated flavonoid glycoside from Epimedium (Yin Yang Huo), exhibits multi-organ pharmacological effects and has emerged as a promising candidate for osteoporosis therapy and bone tissue regeneration because of its capacity to modulate diverse osteogenic, anti-inflammatory, and angiogenic signaling pathways. Preclinical studies in osteoporotic models suggest that ICA improves trabecular microarchitecture and increases bone mineral density. Mechanistically, ICA modulates bone remodeling bidirectionally: it promotes osteoblast differentiation and extracellular matrix mineralization via activation of pro-osteogenic pathways, including Wnt\/\u03b2-catenin and PI3K\/Akt signaling, while simultaneously inhibiting osteoclastogenesis and bone resorption by suppressing RANKL-mediated NF-\u03baB activation, thus reestablishing remodeling equilibrium. Despite these benefits, clinical advancement is hindered by the suboptimal oral bioavailability of ICA, stemming from poor intestinal absorption and extensive first-pass metabolism. To address this, innovative delivery systems have been engineered to enhance localized bioavailability and sustain therapeutic efficacy, such as hydrogel depots, nanoparticle formulations, and 3D-printed scaffolds enabling precise, controlled release. In bone tissue engineering applications, ICA-incorporated biomaterials\u2014either standalone or in combination with osteogenic factors or exosomes\u2014foster a regenerative niche by mitigating inflammation and oxidative stress, while synergistically promoting osteogenesis and angiogenesis, thereby expediting bone defect healing and osseointegration. Overall, these mechanistic elucidations and delivery advancements underscore ICA\u2019s potential as a translational candidate for osteoporosis treatment and bone regenerative therapies. This review aims to critically and systematically synthesize current evidence on ICA-mediated bone repair and regeneration, with a particular emphasis on the molecular regulation of osteogenic signaling, the restoration of bone-remodeling homeostasis, and delivery-system-enabled strategies that may facilitate translational application.<\/jats:p>","DOI":"10.3390\/cells15100935","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:06:26Z","timestamp":1779696386000},"page":"935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plant-Derived Bioactive Ingredients for Osteoporosis and Bone Regeneration: Mechanisms, Pharmacology, and Delivery Strategies"],"prefix":"10.3390","volume":"15","author":[{"given":"Changshun","family":"Li","sequence":"first","affiliation":[{"name":"School of Stomatology, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyu","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengying","family":"Li","sequence":"additional","affiliation":[{"name":"School of Stomatology, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijian","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2688-0889","authenticated-orcid":false,"given":"Meng","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Stomatology, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5960-9174","authenticated-orcid":false,"given":"Jiabin","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Stomatology, Xuzhou Medical University, Xuzhou 221004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hu, W., Si, Y., Xie, X., and Xu, J. (2025). Research Progress on Icariin Promoting Bone Injury Repair and Regeneration. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081174"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157490","DOI":"10.1016\/j.phymed.2025.157490","article-title":"Gut microbiota-metabolite crosstalk mediates icariin\u2019s protection against obesity-induced spermatogenic dysfunction through NF-\u03baB\/AMH axis in Sertoli cells","volume":"149","author":"Huang","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_3","first-page":"785","article-title":"Osteoporosis","volume":"52","author":"Roth","year":"2023","journal-title":"Orthopadie"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/S0140-6736(21)02646-5","article-title":"Drug therapy for osteoporosis in older adults","volume":"399","author":"Reid","year":"2022","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0378-5122(98)00101-7","article-title":"Postmenopausal women without previous or current vasomotor symptoms do not flush after abruptly abandoning estrogen replacement therapy","volume":"31","author":"Hammar","year":"1999","journal-title":"Maturitas"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.mcna.2020.06.004","article-title":"Osteoporosis in Older Adults","volume":"104","author":"Johnston","year":"2020","journal-title":"Med. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1007\/s00198-009-0925-y","article-title":"Osteoporosis in china","volume":"20","author":"Wang","year":"2009","journal-title":"Osteoporos. Int."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Aibar-Almaz\u00e1n, A., Voltes-Mart\u00ednez, A., Castellote-Caballero, Y., Afanador-Restrepo, D.F., Carcel\u00e9n-Fraile, M.D.C., and L\u00f3pez-Ruiz, E. (2022). Current Status of the Diagnosis and Management of Osteoporosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169465"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fu, B., Yu, S., Chen, S., and Hu, B. (2025). Icariin against osteoporosis: A review of advances in molecular mechanisms to biomedical applications. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1688847"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"200","DOI":"10.3892\/mmr.2022.12716","article-title":"Osteoprotective effects of flavonoids: Evidence from in vivo and in vitro studies (Review)","volume":"25","author":"Cao","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Luo, J., Wu, L., Xu, Y., Zhang, J., Zhao, X., and Wang, X. (2025). The therapeutic potential of icariin in the intervention of bone and joint diseases through multiple pathways: A narrative review. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1606912"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13036-024-00425-4","article-title":"Promoting osteogenesis and bone regeneration employing icariin-loaded nanoplatforms","volume":"18","author":"Mohammadzadeh","year":"2024","journal-title":"J. Biol. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Oprita, E.I., Iosageanu, A., and Craciunescu, O. (2022). Progress in Composite Hydrogels and Scaffolds Enriched with Icariin for Osteochondral Defect Healing. Gels, 8.","DOI":"10.3390\/gels8100648"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112533","DOI":"10.1016\/j.intimp.2024.112533","article-title":"Icaritin attenuates ischemia-reperfusion injury by anti-inflammation, anti-oxidative stress, and anti-autophagy in mouse liver","volume":"138","author":"Sun","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6666836","DOI":"10.1155\/2021\/6666836","article-title":"Icariin Promotes the Osteogenesis of Bone Marrow Mesenchymal Stem Cells through Regulating Sclerostin and Activating the Wnt\/\u03b2-Catenin Signaling Pathway","volume":"2021","author":"Gao","year":"2021","journal-title":"Biomed. Res. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113180","DOI":"10.1016\/j.biopha.2022.113180","article-title":"Anti-inflammatory and immunoregulatory effects of icariin and icaritin","volume":"151","author":"Bi","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, N., Song, L., Peng, Y., Wei, L., Long, Z., Wang, C., Liu, Q., and Shi, C. (2025). Kangshujiangu granules improve NAFLD via cross-organ autophagy activation shared with osteoporosis. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1633813"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117761","DOI":"10.1016\/j.taap.2026.117761","article-title":"Icariin regulates osteogenic\/adipogenic differentiation of bone marrow mesenchymal stem cells in postmenopausal osteoporosis, potentially via the AMPK-mTOR-autophagy pathway","volume":"510","author":"Zeng","year":"2026","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_19","first-page":"156","article-title":"Promoting osteoblast-mediated bone formation: A more promising approach for natural products to treat osteoporosis","volume":"24","author":"Hu","year":"2026","journal-title":"Chin. J. Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"156214","DOI":"10.1016\/j.phymed.2024.156214","article-title":"Icariin ameliorates Coxsackievirus B3-induced viral myocarditis by modulating the S100 calcium binding protein A6\/\u03b2-catenin\/c-Myc signaling pathway","volume":"135","author":"Tian","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"113432","DOI":"10.1016\/j.intimp.2024.113432","article-title":"Preventive effects of matrine on LPS-induced inflammation in RAW 264.7 cells and intestinal damage in mice through the TLR4\/NF-\u03baB\/MAPK pathway","volume":"143","author":"Mao","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ahmed, M., Riaz, U., Lv, H., Amjad, M., Ahmed, S., Ali, S., Ghani, M.U., Hua, G., and Yang, L. (2024). Nicotinamide Mononucleotide Restores NAD(+) Levels to Alleviate LPS-Induced Inflammation via the TLR4\/NF-\u03baB\/MAPK Signaling Pathway in Mice Granulosa Cells. Antioxidants, 14.","DOI":"10.3390\/antiox14010039"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1002\/ptr.7057","article-title":"Icariin reduces Glu-induced excitatory neurotoxicity via antioxidative and antiapoptotic pathways in SH-SY5Y cells","volume":"35","author":"Zheng","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"120036","DOI":"10.1016\/j.jep.2025.120036","article-title":"Icariin mitigates depressive-like behavior in rats by regulating mitochondrial function","volume":"350","author":"Zhao","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9974625","DOI":"10.1155\/2021\/9974625","article-title":"Icariin Promotes Survival, Proliferation, and Differentiation of Neural Stem Cells In Vitro and in a Rat Model of Alzheimer\u2019s Disease","volume":"2021","author":"Ma","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e06712","DOI":"10.1002\/advs.202506712","article-title":"Icaritin Ameliorates Cisplatin-Induced Mitochondrial Metabolic Dysfunction-Associated Nephrotoxicity and Synergistically Potentiates Its Antitumor Efficacy","volume":"13","author":"Luo","year":"2026","journal-title":"Adv. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/s41392-023-01543-z","article-title":"Extracellular RNAs-TLR3 signaling contributes to cognitive impairment after chronic neuropathic pain in mice","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"115303","DOI":"10.1016\/j.expneurol.2025.115303","article-title":"Icariin attenuates oxidative stress via SIRT1\/PGC-1\u03b1 pathway in SAH mice","volume":"390","author":"Lei","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107274","DOI":"10.1016\/j.ejps.2025.107274","article-title":"IFN-\u03b3 enhances Poly(I:C)-induced necroptosis and immunogenic cell death via TLR3 upregulation in cholangiocarcinoma cells","volume":"214","author":"Lomphithak","year":"2025","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1080\/13880209.2021.1991959","article-title":"Icariin inhibits the expression of IL-1\u03b2, IL-6 and TNF-\u03b1 induced by OGD\/R through the IRE1\/XBP1s pathway in microglia","volume":"59","author":"Mo","year":"2021","journal-title":"Pharm. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33763","DOI":"10.1038\/s41598-025-98803-5","article-title":"Icariin inhibits proliferation and migration of VSMCs via LncRNA H19 competitively binding to HuR","volume":"15","author":"Zhang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109611","DOI":"10.1016\/j.intimp.2022.109611","article-title":"Icariin alleviates atherosclerosis by regulating the miR-205-5p\/ERBB4\/AKT signaling pathway","volume":"114","author":"Huang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115969","DOI":"10.1016\/j.taap.2022.115969","article-title":"Icariin promotes mouse Leydig cell testosterone synthesis via the Esr1\/Src\/Akt\/Creb\/Sf-1 pathway","volume":"441","author":"Sun","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1136\/gutjnl-2023-329543","article-title":"Lactobacillus gallinarum-derived metabolites boost anti-PD1 efficacy in colorectal cancer by inhibiting regulatory T cells through modulating IDO1\/Kyn\/AHR axis","volume":"72","author":"Fong","year":"2023","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s13046-024-03063-2","article-title":"Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1\/IGFBP2 axis to suppress the development of prostate cancer","volume":"43","author":"Xu","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"102297","DOI":"10.1016\/j.redox.2022.102297","article-title":"Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1\/M2 phenotypic polarization","volume":"52","author":"Wang","year":"2022","journal-title":"Redox Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"155217","DOI":"10.1016\/j.phymed.2023.155217","article-title":"The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-\u03baB p65 inhibition","volume":"123","author":"Lu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.rvsc.2021.07.014","article-title":"Icariin and its phosphorylated derivatives reduce duck hepatitis A virus serotype 1-induced oxidative stress and inflammatory damage in duck embryonic hepatocytes through mitochondrial regulation","volume":"139","author":"Xiong","year":"2021","journal-title":"Res. Vet. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/hmg\/ddac168","article-title":"An enhancer variant associated with breast cancer susceptibility in Black women regulates TNFSF10 expression and antitumor immunity in triple-negative breast cancer","volume":"32","author":"Han","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12935-024-03266-9","article-title":"Icariin exerts anti-tumor activity by inducing autophagy via AMPK\/mTOR\/ULK1 pathway in triple-negative breast cancer","volume":"24","author":"Zhao","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13020-023-00788-8","article-title":"Effects of genus Epimedium in the treatment of osteoarthritis and relevant signaling pathways","volume":"18","author":"Tong","year":"2023","journal-title":"Chin. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"116957","DOI":"10.1016\/j.jep.2023.116957","article-title":"A systematic review of traditional uses, phytochemistry, pharmacology and toxicity of Epimedium koreanum Nakai","volume":"318","author":"Qian","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"119161","DOI":"10.1016\/j.jep.2024.119161","article-title":"Research progress of main components from Epimedii Folium (Yinyanghuo) in the treatment of male reproductive dysfunction and application & development status of Epimedii Folium","volume":"340","author":"Zhao","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hai, Y., Zuo, L., Wang, M., Zhang, R., Wang, M., Ren, L., Yang, C., and Wang, J. (2023). Icariin Alleviates Nonalcoholic Fatty Liver Disease in Polycystic Ovary Syndrome by Improving Liver Fatty Acid Oxidation and Inhibiting Lipid Accumulation. Molecules, 28.","DOI":"10.3390\/molecules28020517"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"121350","DOI":"10.1016\/j.talanta.2020.121350","article-title":"Extraction of activated epimedium glycosides in vivo and in vitro by using bifunctional-monomer chitosan magnetic molecularly imprinted polymers and identification by UPLC-Q-TOF-MS","volume":"219","author":"Zhang","year":"2020","journal-title":"Talanta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1055\/a-0806-7673","article-title":"Pharmacokinetics of Prenylflavonoids following Oral Ingestion of Standardized Epimedium Extract in Humans","volume":"85","author":"Teo","year":"2019","journal-title":"Planta Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, X., Tang, B., Wen, S., Wang, Y., Pan, C., Qu, L., Yin, Y., and Wei, Y. (2023). Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium. Molecules, 28.","DOI":"10.3390\/molecules28207173"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"116151","DOI":"10.1016\/j.jpba.2024.116151","article-title":"In vitro simulated saliva, gastric, and intestinal digestion followed by faecal fermentation reveals a potential modulatory activity of Epimedium on human gut microbiota","volume":"245","author":"Li","year":"2024","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tong, D., Chen, L., Jiang, Z., Ye, X., Ma, M., Ye, A., and Xu, J. (2025). Progress in the application of epimedium and its major bioactive components in the treatment of orthopedic diseases. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1628602"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3892\/mmr.2022.12642","article-title":"Icariin attenuates thioacetamide-induced bone loss via the RANKL-p38\/ERK-NFAT signaling pathway","volume":"25","author":"Cheng","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ding, Y., Yu, B., Zhou, S., Ding, C., Zhang, Z., Xu, S., and Xu, Z. (2023). Improvement of solubility and pharmacokinetic profile of hepatoprotector icariin through complexation with HP-\u03b3-cyclodextrin. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1138686"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"P\u0103cularu-Burada, B., C\u00eer\u00eec, A.I., and Begea, M. (2024). Anti-Aging Effects of Flavonoids from Plant Extracts. Foods, 13.","DOI":"10.3390\/foods13152441"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Szab\u00f3, R., R\u00e1cz, C.P., and Dulf, F.V. (2022). Bioavailability Improvement Strategies for Icariin and Its Derivates: A Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147519"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"116631","DOI":"10.1016\/j.jpba.2024.116631","article-title":"Comparisons of the bioavailability of icariin, icariside II, and epimedin C in rats after oral administration of total flavonoids of Epimedium brevicornu Maxim. and its three formulations","volume":"255","author":"Ding","year":"2025","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.1021\/acs.jafc.5c16422","article-title":"A Hyperthermostable Archaeal GH78 Rhamnosidase Efficiently Hydrolyzes Flavonoid Glycosides for Juice Debittering","volume":"74","author":"Curci","year":"2026","journal-title":"J. Agric. Food Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/08982104.2025.2602599","article-title":"Development of icariin-loaded bone-targeting liposomes and its anti-osteoporosis effects and mechanism","volume":"36","author":"Sheng","year":"2026","journal-title":"J. Liposome Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"214773","DOI":"10.1016\/j.bioadv.2026.214773","article-title":"A biointerface-engineered gold nanocluster platform for icariin delivery: Dual-pathway modulation of osteoblast and osteoclast dynamics in osteoporosis therapy","volume":"183","author":"Wang","year":"2026","journal-title":"Biomater. Adv."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113892","DOI":"10.1016\/j.biopha.2022.113892","article-title":"The pulmonary pharmacokinetics and anti-inflammatory effects after intratracheal and intravenous administration of Chuankezhi injection","volume":"156","author":"Cong","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"142481","DOI":"10.1016\/j.ijbiomac.2025.142481","article-title":"Rhamnosidase from Parabacteroides distasonis exhibit the catabolism of epimedin C in the human gut microbiota","volume":"309","author":"Ding","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2016.09.027","article-title":"Layer-by-layer nanocoating of live Bacille-Calmette-Gu\u00e9rin mycobacteria with poly(I:C) and chitosan enhances pro-inflammatory activation and bactericidal capacity in murine macrophages","volume":"111","author":"Speth","year":"2016","journal-title":"Biomaterials"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"111580","DOI":"10.1016\/j.cbi.2025.111580","article-title":"D-limonene complexed with hydroxypropyl-\u03b2-cyclodextrin prevents impaired cardiac excitation-contraction coupling by reducing oxidative stress and cardiac apoptosis in an animal model of cardiotoxicity induced by doxorubicin","volume":"418","author":"Souza","year":"2025","journal-title":"Chem. Biol. Interact."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1016\/j.xphs.2022.03.021","article-title":"Liquiritin-Hydroxypropyl-Beta-Cyclodextrin Inclusion Complex: Preparation, Characterization, Bioavailability and Antitumor Activity Evaluation","volume":"111","author":"Wang","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2169414","DOI":"10.1080\/10717544.2023.2169414","article-title":"Nanotherapy for bone repair: Milk-derived small extracellular vesicles delivery of icariin","volume":"30","author":"Yu","year":"2023","journal-title":"Drug Deliv."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Negrescu, A.M., Mitran, V., Draghicescu, W., Popescu, S., Pirvu, C., Ionascu, I., Soare, T., Uzun, S., Croitoru, S.M., and Cimpean, A. (2022). TiO2 Nanotubes Functionalized with Icariin for an Attenuated In Vitro Immune Response and Improved In Vivo Osseointegration. J. Funct. Biomater., 13.","DOI":"10.3390\/jfb13020043"},{"key":"ref_65","first-page":"100799","article-title":"Bone mesenchymal stem cell-derived exosomes involved co-delivery and synergism effect with icariin via mussel-inspired multifunctional hydrogel for cartilage protection","volume":"18","author":"Zeng","year":"2023","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Gao, L., and Zhang, S.Q. (2022). Antiosteoporosis Effects, Pharmacokinetics, and Drug Delivery Systems of Icaritin: Advances and Prospects. Pharmaceuticals, 15.","DOI":"10.3390\/ph15040397"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"125001","DOI":"10.1016\/j.ijbiomac.2023.125001","article-title":"Instantaneous self-healing and strongly adhesive self-adaptive hyaluronic acid-based hydrogel for controlled drug release to promote tendon wound healing","volume":"242","author":"Ren","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"101374","DOI":"10.1016\/j.mtbio.2024.101374","article-title":"Sequential delivery of IL-10 and icariin using nanoparticle\/hydrogel hybrid system for prompting bone defect repair","volume":"29","author":"Li","year":"2024","journal-title":"Mater. Today Bio"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1007\/s10646-025-02862-3","article-title":"Polycaprolactam microplastics reduce allelopathic potential of Iris pseudacorus via toxic effects on stimulatory bacteria","volume":"34","author":"Zuo","year":"2025","journal-title":"Ecotoxicology"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Trejos-Soto, L., Rivas-Hern\u00e1ndez, G.O., Mora-Bola\u00f1os, R., Vargas-Valverde, N., Valerio, A., Ulloa-Fern\u00e1ndez, A., Oviedo-Quir\u00f3s, J., Garc\u00eda-Pi\u00f1eres, A., Paniagua, S.A., and Centeno-Cerdas, C. (2024). Composites of Polylactic Acid with Diatomaceous Earth for 3D-Printing Biocompatible Scaffolds: A Systematic Study of Their Mechanical, Thermal, and Biocompatibility Properties. Bioengineering, 11.","DOI":"10.3390\/bioengineering11111059"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ijbiomac.2022.11.041","article-title":"In vitro biodegradation, cytotoxicity, and biocompatibility of polylactic acid\/napier cellulose nanofiber scaffold composites","volume":"223","author":"Revati","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1080\/10717544.2021.1938756","article-title":"PLGA-based biodegradable microspheres in drug delivery: Recent advances in research and application","volume":"28","author":"Su","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e2308875","DOI":"10.1002\/adma.202308875","article-title":"Time-Sequential and Multi-Functional 3D Printed MgO2\/PLGA Scaffold Developed as a Novel Biodegradable and Bioactive Bone Substitute for Challenging Postsurgical Osteosarcoma Treatment","volume":"36","author":"Li","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mazurek, \u0141., Szudzik, M., Rybka, M., and Konop, M. (2022). Silk Fibroin Biomaterials and Their Beneficial Role in Skin Wound Healing. Biomolecules, 12.","DOI":"10.3390\/biom12121852"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.actbio.2022.02.004","article-title":"Optimizing the bio-degradability and biocompatibility of a biogenic collagen membrane through cross-linking and zinc-doped hydroxyapatite","volume":"143","author":"Wu","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ijbiomac.2022.05.018","article-title":"Biocompatibility and immunostimulatory properties of fish collagen and shrimp chitosan towards peripheral blood mononuclear cells (PBMCs)","volume":"210","author":"Portela","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e2302626","DOI":"10.1002\/adhm.202302626","article-title":"Hyaluronic Acid-Based Reactive Oxygen Species-Responsive Multifunctional Injectable Hydrogel Platform Accelerating Diabetic Wound Healing","volume":"13","author":"Shi","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e2400513","DOI":"10.1002\/smtd.202400513","article-title":"Hyaluronic Acid Receptor-Mediated Nanomedicines and Targeted Therapy","volume":"8","author":"Ouyang","year":"2024","journal-title":"Small Methods"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1177\/08853282241243010","article-title":"Synthesis and characterization of chitosan for medical applications: A review","volume":"38","author":"Isa","year":"2024","journal-title":"J. Biomater. Appl."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"121318","DOI":"10.1016\/j.carbpol.2023.121318","article-title":"Recent advances in chitosan-based materials; The synthesis, modifications and biomedical applications","volume":"321","author":"Iqbal","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"123909","DOI":"10.1016\/j.carbpol.2025.123909","article-title":"Ultrasound-triggered injectable piezoelectric nanocomposite hyaluronic acid-based hydrogel for modulating inflammation and chondrogenesis in osteoarthritis treatment","volume":"367","author":"Lin","year":"2025","journal-title":"Carbohydr. Polym."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Shi, M., Gao, Y., Lee, L., Song, T., Zhou, J., Yan, L., and Li, Y. (2022). Adaptive Gelatin Microspheres Enhanced Stem Cell Delivery and Integration with Diabetic Wounds to Activate Skin Tissue Regeneration. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.813805"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1089\/wound.2022.0034","article-title":"Gelatin Microspheres Loaded with Wharton\u2019s Jelly Mesenchymal Stem Cells Promote Acute Full-Thickness Skin Wound Healing and Regeneration in Mice","volume":"12","author":"Jiao","year":"2023","journal-title":"Adv. Wound Care"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s40729-024-00567-6","article-title":"In vivo validation of osteoinductivity and biocompatibility of BMP-2 enriched calcium phosphate cement alongside retrospective description of its clinical adverse events","volume":"10","author":"Wang","year":"2024","journal-title":"Int. J. Implant. Dent."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"115049","DOI":"10.1016\/j.addr.2023.115049","article-title":"Biosafety of mesoporous silica nanoparticles; towards clinical translation","volume":"201","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jcis.2024.05.209","article-title":"Enhancing bone regeneration and immunomodulation via gelatin methacryloyl hydrogel-encapsulated exosomes from osteogenic pre-differentiated mesenchymal stem cells","volume":"672","author":"Li","year":"2024","journal-title":"J. Colloid. Interface Sci."},{"key":"ref_87","first-page":"11","article-title":"Application of gelatin methacryloyl\/minocycline-chitosan-nanoparticles composite hydrogel for the treatment of periodontitis","volume":"41","author":"You","year":"2023","journal-title":"Hua Xi Kou Qiang Yi Xue Za Zhi"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12938-022-01052-0","article-title":"Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration","volume":"21","author":"Liu","year":"2022","journal-title":"Biomed. Eng. Online"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1039\/C9TB02901J","article-title":"Integrating silicon\/zinc dual elements with PLGA microspheres in calcium phosphate cement scaffolds synergistically enhances bone regeneration","volume":"8","author":"Liang","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"102476","DOI":"10.1016\/j.mtbio.2025.102476","article-title":"Icariin-loaded GelMa hydrogel encapsulated potassium sodium niobate biomimetic piezoelectric scaffold regulates macrophage polarization to accelerate bone defect repair","volume":"35","author":"Wang","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1044\/2024_AJA-24-00131","article-title":"An Evaluation of the Psychometric Properties of the Short Form of the Speech, Spatial and Qualities of Hearing Scale in Swedish: Online Versus Paper-and-Pen","volume":"33","author":"Ahlberg","year":"2024","journal-title":"Am. J. Audiol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Popazova, O., Belenichev, I., Bukhtiyarova, N., Ryzhenko, V., Gorchakova, N., Oksenych, V., and Kamyshnyi, O. (2025). Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia-Focus on the NO System. Antioxidants, 14.","DOI":"10.20944\/preprints202504.0558.v1"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4684962","DOI":"10.1155\/2017\/4684962","article-title":"Pharmacokinetics, Tissue Distribution, and Metabolism Study of Icariin in Rat","volume":"2017","author":"Xu","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Zhao, J., and Zhang, W. (2025). Icariin and related metabolites in fibrosis management: Pharmacological properties and molecular mechanism. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1619581"},{"key":"ref_95","first-page":"1071","article-title":"Small intestinal bacterial overgrowth (SIBO)\u2014Therapy, nutrition, microbiome","volume":"149","author":"Sellge","year":"2024","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"skae073","DOI":"10.1093\/jas\/skae073","article-title":"Calcium trafficking and gastrointestinal physiology following an acute lipopolysaccharide challenge in pigs","volume":"102","author":"Opgenorth","year":"2024","journal-title":"J. Anim. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"wraf141","DOI":"10.1093\/ismejo\/wraf141","article-title":"Targeting Catenibacterium mitsuokai with icariin modulates gut microbiota and improves hepatic lipid metabolism in intrauterine growth restriction","volume":"19","author":"Wei","year":"2025","journal-title":"ISME J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"112642","DOI":"10.1016\/j.biopha.2022.112642","article-title":"Icariin and its metabolites as potential protective phytochemicals against cardiovascular disease: From effects to molecular mechanisms","volume":"147","author":"Zeng","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Liu, W., Li, X., Li, N., Mi, Z., Li, N., and Che, J. (2023). UPLC-MS\/MS method for Icariin and metabolites in whole blood of C57 mice: Development, validation, and pharmacokinetics study. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1195525"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"122125","DOI":"10.1016\/j.biomaterials.2023.122125","article-title":"Osteoporosis remission via an anti-inflammaging effect by icariin activated autophagy","volume":"297","author":"Bai","year":"2023","journal-title":"Biomaterials"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Ashenova, A., Daniyarov, A., Molkenov, A., Sharip, A., Zinovyev, A., and Kairov, U. (2021). Meta-Analysis of Esophageal Cancer Transcriptomes Using Independent Component Analysis. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.683632"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.bcp.2017.04.010","article-title":"Icariin protects against glucocorticoid induced osteoporosis, increases the expression of the bone enhancer DEC1 and modulates the PI3K\/Akt\/GSK3\u03b2\/\u03b2-catenin integrated signaling pathway","volume":"136","author":"Hu","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_103","first-page":"5882","article-title":"Icariin inhibits thioacetamide-induced osteoclast differentiation through RANKL-p38\/ERK-NFAT pathway","volume":"47","author":"Cheng","year":"2022","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.biopha.2017.01.050","article-title":"Icariin influences adipogenic differentiation of stem cells affected by osteoblast-osteoclast co-culture and clinical research adipogenic","volume":"88","author":"Zhang","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"787","DOI":"10.2174\/138920007782798171","article-title":"Multidrug resistance associated proteins as determining factors of pharmacokinetics and pharmacodynamics of drugs","volume":"8","author":"Yu","year":"2007","journal-title":"Curr. Drug Metab."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"8191","DOI":"10.18632\/aging.103133","article-title":"The shared KEGG pathways between icariin-targeted genes and osteoporosis","volume":"12","author":"Yu","year":"2020","journal-title":"Aging"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"12389","DOI":"10.2147\/IJN.S483621","article-title":"Icariin-Enhanced Osteoclast-Derived Exosomes Promote Repair of Infected Bone Defects by Regulating Osteoclast and Osteoblast Communication","volume":"19","author":"Zhang","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e15297","DOI":"10.1111\/1756-185X.15297","article-title":"METTL14 promotes chondrocyte ferroptosis in osteoarthritis via m6A modification of GPX4","volume":"27","author":"Liu","year":"2024","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"112010","DOI":"10.1016\/j.intimp.2024.112010","article-title":"Icariin inhibits chondrocyte ferroptosis and alleviates osteoarthritis by enhancing the SLC7A11\/GPX4 signaling","volume":"133","author":"Xiao","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e35307","DOI":"10.1016\/j.heliyon.2024.e35307","article-title":"Investigating the anti-inflammatory effects of icariin: A combined meta-analysis and machine learning study","volume":"10","author":"Guo","year":"2024","journal-title":"Heliyon"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1515\/jcim-2024-0405","article-title":"Icariin as a therapeutic agent in breast cancer: Modulating apoptosis and suppressing proliferation","volume":"22","author":"Goyal","year":"2025","journal-title":"J. Complement. Integr. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"152888","DOI":"10.1016\/j.bbrc.2025.152888","article-title":"Icariin regulates the Hippo\/TAZ signaling pathway to promote osteogenic differentiation and bone remodeling in osteoporosis","volume":"792","author":"Zhao","year":"2025","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"101603","DOI":"10.1016\/j.jbc.2022.101603","article-title":"Endosomal TLR3 signaling in stromal osteoblasts induces prostaglandin E2-mediated inflammatory periodontal bone resorption","volume":"298","author":"Tominari","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Zhang, J., Fan, F., Liu, A., Zhang, C., Li, Q., Zhang, C., He, F., and Shang, M. (2022). Icariin: A Potential Molecule for Treatment of Knee Osteoarthritis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.811808"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Liu, F.Y., Ding, D.N., Wang, Y.R., Liu, S.X., Peng, C., Shen, F., Zhu, X.Y., Li, C., Tang, L.P., and Han, F.J. (2023). Icariin as a potential anticancer agent: A review of its biological effects on various cancers. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1216363"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12958-021-00851-9","article-title":"Icariin improves testicular dysfunction via enhancing proliferation and inhibiting mitochondria-dependent apoptosis pathway in high-fat diet and streptozotocin-induced diabetic rats","volume":"19","author":"He","year":"2021","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"7320","DOI":"10.1111\/jcmm.14589","article-title":"Icariin promotes angiogenesis in glucocorticoid-induced osteonecrosis of femoral heads: In vitro and in vivo studies","volume":"23","author":"Yu","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.biopha.2018.09.071","article-title":"Icariin and mesenchymal stem cells synergistically promote angiogenesis and neurogenesis after cerebral ischemia via PI3K and ERK1\/2 pathways","volume":"108","author":"Liu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1177\/039139881203500905","article-title":"Angiopoietin-2\/Tie2 signaling involved in TNF-\u03b1 induced peritoneal angiogenesis","volume":"35","author":"Yuan","year":"2012","journal-title":"Int. J. Artif. Organs"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1080\/21655979.2021.2011637","article-title":"Icariin activates autophagy to trigger TGF\u03b21 upregulation and promote angiogenesis in EA.hy926 human vascular endothelial cells","volume":"13","author":"Li","year":"2022","journal-title":"Bioengineered"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"769","DOI":"10.4239\/wjd.v15.i4.769","article-title":"Icariin accelerates bone regeneration by inducing osteogenesis-angiogenesis coupling in rats with type 1 diabetes mellitus","volume":"15","author":"Zheng","year":"2024","journal-title":"World J. Diabetes"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Hu, W., Xie, X., and Xu, J. (2025). Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K\/Akt Pathway. Cells, 14.","DOI":"10.3390\/cells14151214"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"108861","DOI":"10.1016\/j.intimp.2022.108861","article-title":"Impact of Icariin and its derivatives on inflammatory diseases and relevant signaling pathways","volume":"108","author":"Luo","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.bbrc.2022.02.023","article-title":"Icariin inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells via inhibition of reactive oxygen species production by reducing the expression of NOX1 and NOX4","volume":"600","author":"Ji","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e00586","DOI":"10.1002\/mgg3.586","article-title":"Icariin inhibits chondrocyte apoptosis and angiogenesis by regulating the TDP-43 signaling pathway","volume":"7","author":"Huang","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Sinberger, L.A., Keren-Khadmy, N., Goldberg, A., Peretz-Yablonski, T., Sonnenblick, A., and Salmon-Divon, M. (2025). Revealing the Angiogenic Signature of FH-Deficient Breast Cancer: Genomic Profiling and Clinical Implications. Cancers, 17.","DOI":"10.3390\/cancers17182942"},{"key":"ref_127","first-page":"641","article-title":"Lymphatic incorporated biomimetic scaffold enhances Osteoangio-lymphogenic coupling via HIF-1\u03b1 mediated mitochondrial reprogramming for osteoporotic bone repair","volume":"56","author":"Sun","year":"2026","journal-title":"Bioact. Mater."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"113841","DOI":"10.1016\/j.phytochem.2023.113841","article-title":"Liver protecting effects and molecular mechanisms of icariin and its metabolites","volume":"215","author":"Ma","year":"2023","journal-title":"Phytochemistry"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3159","DOI":"10.21037\/tau-2025-395","article-title":"Icariside II attenuates renal fibrosis through mTOR signaling modulation: An integrated approach combining network pharmacology, molecular dynamics, and in vitro validation","volume":"14","author":"Ding","year":"2025","journal-title":"Transl. Androl. Urol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.4049\/jimmunol.139.7.2398","article-title":"Biochemical and functional properties of serine esterases in acidic cytoplasmic granules of cytotoxic T lymphocytes","volume":"139","author":"Henkart","year":"1987","journal-title":"J. Immunol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"902","DOI":"10.5152\/tjg.2020.19568","article-title":"Berberine inhibits liver damage in rats with non-alcoholic fatty liver disease by regulating TLR4\/MyD88\/NF-\u03baB pathway","volume":"31","author":"Wang","year":"2020","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e23566","DOI":"10.1002\/jbt.23566","article-title":"Icariin alleviates high-fat diet-induced nonalcoholic fatty liver disease via up-regulating miR-206 to mediate NF-\u03baB and MAPK pathways","volume":"38","author":"Zhao","year":"2024","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Wu, C.T., Chen, M.C., Liu, S.H., Yang, T.H., Long, L.H., Guan, S.S., and Chen, C.M. (2021). Bioactive Flavonoids Icaritin and Icariin Protect against Cerebral Ischemia-Reperfusion-Associated Apoptosis and Extracellular Matrix Accumulation in an Ischemic Stroke Mouse Model. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111719"},{"key":"ref_134","first-page":"1407","article-title":"AMPK\/PGC-1\u03b1\/GLUT4-Mediated Effect of Icariin on Hyperlipidemia-Induced Non-Alcoholic Fatty Liver Disease and Lipid Metabolism Disorder in Mice","volume":"86","author":"Lin","year":"2021","journal-title":"Biochemistry"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Choi, J., Choi, H., and Chung, J. (2023). Icariin Supplementation Suppresses the Markers of Ferroptosis and Attenuates the Progression of Nonalcoholic Steatohepatitis in Mice Fed a Methionine Choline-Deficient Diet. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512510"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.redox.2018.08.018","article-title":"Suppression of hERG K+ current and cardiac action potential prolongation by 4-hydroxynonenal via dual mechanisms","volume":"19","author":"Choi","year":"2018","journal-title":"Redox Biol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1159\/000487955","article-title":"Icariin Improves Sepsis-Induced Mortality and Acute Kidney Injury","volume":"102","author":"Xie","year":"2018","journal-title":"Pharmacology"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.2147\/DDDT.S369100","article-title":"Icariin and Competing Endogenous RNA Network: A Potential Protective Strategy Against Contrast-Induced Acute Kidney Injury","volume":"16","author":"Lin","year":"2022","journal-title":"Drug Des. Devel Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"152917","DOI":"10.1016\/j.phymed.2019.152917","article-title":"The antifibrotic and anti-inflammatory effects of icariin on the kidney in a unilateral ureteral obstruction mouse model","volume":"59","author":"Chen","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"7398","DOI":"10.3892\/mmr.2017.7513","article-title":"Icariin improves acute kidney injury and proteinuria in a rat model of pregnancy-induced hypertension","volume":"16","author":"Zhang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s00395-024-01067-9","article-title":"Empagliflozin prevents heart failure through inhibition of the NHE1-NO pathway, independent of SGLT2","volume":"119","author":"Chen","year":"2024","journal-title":"Basic. Res. Cardiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/FJC.0000000000000696","article-title":"NLRP3 Inflammasome in Cardioprotective Signaling","volume":"74","author":"Zuurbier","year":"2019","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Duan, S., Ding, Z., Liu, C., Wang, X., and Dai, E. (2024). Icariin suppresses nephrotic syndrome by inhibiting pyroptosis and epithelial-to-mesenchymal transition. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0298353"},{"key":"ref_144","first-page":"517","article-title":"Icariin ameliorates oxidative stress-induced inflammation, apoptosis, and heart failure in isoproterenol-challenged Wistar rats","volume":"26","author":"Sharma","year":"2023","journal-title":"Iran. J. Basic. Med. Sci."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1161\/CIRCULATIONAHA.124.068858","article-title":"Essential Role of the RI\u03b1 Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development","volume":"150","author":"Bedioune","year":"2024","journal-title":"Circulation"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Gambaryan, S. (2022). The Role of NO\/sGC\/cGMP\/PKG Signaling Pathway in Regulation of Platelet Function. Cells, 11.","DOI":"10.3390\/cells11223704"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.biopha.2016.08.016","article-title":"Icariin attenuated oxidative stress induced-cardiac apoptosis by mitochondria protection and ERK activation","volume":"83","author":"Song","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s11655-013-1583-7","article-title":"Icariin promotes self-renewal of neural stem cells: An involvement of extracellular regulated kinase signaling pathway","volume":"20","author":"Huang","year":"2014","journal-title":"Chin. J. Integr. Med."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"153607","DOI":"10.1016\/j.phymed.2021.153607","article-title":"Cardioprotective effect of icariin against myocardial fibrosis and its molecular mechanism in diabetic cardiomyopathy based on network pharmacology: Role of ICA in DCM","volume":"91","author":"Zhang","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1159\/000505408","article-title":"Icariin Attenuates Diabetic Cardiomyopathy and Downregulates Extracellular Matrix Proteins in Heart Tissue of Type 2 Diabetic Rats","volume":"105","author":"Qiao","year":"2020","journal-title":"Pharmacology"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1186\/s40001-023-01588-4","article-title":"Icariin improves cardiac function and remodeling via the TGF-\u03b21\/Smad signaling pathway in rats following myocardial infarction","volume":"28","author":"Jia","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_152","first-page":"2478","article-title":"The mechanism of Epimedium in the treatment of coronary atherosclerotic heart disease based on network pharmacology, molecular docking, and in vitro studies","volume":"26","author":"Xin","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"155717","DOI":"10.1016\/j.phymed.2024.155717","article-title":"Qiangxinyin formula protects against isoproterenol-induced cardiac hypertrophy","volume":"130","author":"Zhou","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4838650","DOI":"10.1155\/2022\/4838650","article-title":"Network Pharmacology and Experimental Validation to Reveal Effects and Mechanisms of Icariin Combined with Nobiletin against Chronic Obstructive Pulmonary Diseases","volume":"2022","author":"Lu","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"28118","DOI":"10.1007\/s11356-022-23987-6","article-title":"Effect of TLR3\/dsRNA complex inhibitor on Poly(I:C)-induced airway inflammation in Swiss albino mice","volume":"30","author":"Arora","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"154890","DOI":"10.1016\/j.phymed.2023.154890","article-title":"Molecular mechanisms and therapeutic potential of icariin in the treatment of Alzheimer\u2019s disease","volume":"116","author":"Zheng","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_157","first-page":"3833","article-title":"Icariin modulates the sirtuin\/NF-\u03baB pathway and exerts anti-aging effects in human lung fibroblasts","volume":"22","author":"Xu","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"e3718","DOI":"10.1002\/jgm.3718","article-title":"Icariin attenuates asthmatic airway inflammation via modulating alveolar macrophage activation based on network pharmacology and in vivo experiments","volume":"26","author":"Zhu","year":"2024","journal-title":"J. Gene Med."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Wang, Q., Zuurbier, C.J., Huhn, R., Torregroza, C., Hollmann, M.W., Preckel, B., van den Brom, C.E., and Weber, N.C. (2023). Pharmacological Cardioprotection against Ischemia Reperfusion Injury-The Search for a Clinical Effective Therapy. Cells, 12.","DOI":"10.3390\/cells12101432"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Hu, L., Li, L., Zhang, H., Li, Q., Jiang, S., Qiu, J., Sun, J., and Dong, J. (2019). Inhibition of airway remodeling and inflammatory response by Icariin in asthma. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2743-x"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"121650","DOI":"10.1016\/j.jep.2026.121650","article-title":"Protective effects of the ethyl acetate fraction from Madeng\u2019ai on lipopolysaccharide-induced acute lung injury in mice: Insights from integrated multi-omics analysis","volume":"366","author":"Zhang","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"173032","DOI":"10.1016\/j.ejphar.2020.173032","article-title":"Icariin reduces LPS-induced acute lung injury in mice undergoing bilateral adrenalectomy by regulating GR\u03b1","volume":"876","author":"Sun","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"111802","DOI":"10.1016\/j.intimp.2024.111802","article-title":"Icariin ameliorates LPS-induced acute lung injury in mice via complement C5a-C5aR1 and TLR4 signaling pathways","volume":"131","author":"Guo","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1055\/a-0753-0400","article-title":"Icariin Improves Functional Behavior in a Mouse Model of Traumatic Brain Injury and Promotes Synaptic Plasticity Markers","volume":"85","author":"Joo","year":"2019","journal-title":"Planta Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/cjp2.67","article-title":"Pulmonary adenocarcinoma with mucin production modulates phenotype according to common genetic traits: A reappraisal of mucinous adenocarcinoma and colloid adenocarcinoma","volume":"3","author":"Sonzogni","year":"2017","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s11655-018-2823-z","article-title":"Icariin Improves Cognitive Impairment after Traumatic Brain Injury by Enhancing Hippocampal Acetylation","volume":"24","author":"Zhang","year":"2018","journal-title":"Chin. J. Integr. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.18632\/aging.203893","article-title":"The neuroprotective effects of icariin on ageing, various neurological, neuropsychiatric disorders, and brain injury induced by radiation exposure","volume":"14","author":"Li","year":"2022","journal-title":"Aging"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.neuropharm.2010.03.017","article-title":"Icariin protects against brain injury by enhancing SIRT1-dependent PGC-1alpha expression in experimental stroke","volume":"59","author":"Zhu","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.intimp.2015.11.035","article-title":"Icariin attenuates cerebral ischemia-reperfusion injury through inhibition of inflammatory response mediated by NF-\u03baB, PPAR\u03b1 and PPAR\u03b3 in rats","volume":"30","author":"Xiong","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00381-020-04690-8","article-title":"Neuroprotective effects of icariin in neonatal hypoxia-ischemic brain damage via its anti-apoptotic property","volume":"37","author":"Wang","year":"2021","journal-title":"Childs Nerv. Syst."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1097\/GME.0000000000000673","article-title":"Bone mass improved effect of icariin for postmenopausal osteoporosis in ovariectomy-induced rats: A meta-analysis and systematic review","volume":"23","author":"Xu","year":"2016","journal-title":"Menopause"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.pharmthera.2016.01.015","article-title":"Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health","volume":"162","author":"Indran","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.3892\/ijmm.2014.1952","article-title":"Effects of icariin on the regulation of the OPG-RANKL-RANK system are mediated through the MAPK pathways in IL-1\u03b2-stimulated human SW1353 chondrosarcoma cells","volume":"34","author":"Wang","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1111\/j.1476-5381.2009.00593.x","article-title":"Icariin protects against bone loss induced by oestrogen deficiency and activates oestrogen receptor-dependent osteoblastic functions in UMR 106 cells","volume":"159","author":"Mok","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"941","DOI":"10.17219\/acem\/174078","article-title":"Icariin ameliorates osteoporosis by activating autophagy in ovariectomized rats","volume":"33","author":"Zou","year":"2024","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3892\/mmr.2015.3369","article-title":"Icariin recovers the osteogenic differentiation and bone formation of bone marrow stromal cells from a rat model of estrogen deficiency-induced osteoporosis","volume":"12","author":"Luo","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"e5686","DOI":"10.1002\/bmc.5686","article-title":"Screening of superior anti-osteoporotic flavonoids from Epimedii Folium with dual effects of reversing iron overload and promoting osteogenesis","volume":"37","author":"Jiang","year":"2023","journal-title":"Biomed. Chromatogr."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1039\/D1TB02802B","article-title":"Icariin-loaded sulfonated polyetheretherketone with osteogenesis promotion and osteoclastogenesis inhibition properties via immunomodulation for advanced osseointegration","volume":"10","author":"Chai","year":"2022","journal-title":"J. Mater. Chem. B"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"115900","DOI":"10.1016\/j.foodres.2025.115900","article-title":"Lipid peroxidation inhibition by icaritin and its glycosides as a strategy to combat iron overload-induced osteoporosis in zebrafish","volume":"203","author":"Yan","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"9375","DOI":"10.1039\/D4TB00772G","article-title":"Small intestine submucosa decorated 3D printed scaffold accelerated diabetic bone regeneration by ameliorating the microenvironment","volume":"12","author":"Tan","year":"2024","journal-title":"J. Mater. Chem. B"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"153413","DOI":"10.1016\/j.phymed.2020.153413","article-title":"Icariin ameliorates estrogen-deficiency induced bone loss by enhancing IGF-I signaling via its crosstalk with non-genomic ER\u03b1 signaling","volume":"82","author":"Zhou","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Wang, S., Wang, S., Wang, X., Xu, Y., Zhang, X., Han, Y., Yan, H., Liu, L., Wang, L., and Ye, H. (2022). Effects of Icariin on Modulating Gut Microbiota and Regulating Metabolite Alterations to Prevent Bone Loss in Ovariectomized Rat Model. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.874849"},{"key":"ref_183","first-page":"600","article-title":"Mechanism of icariin in promoting osteogenic differentiation of BMSCs and improving bone metabolism disorders through caveolin-1\/Hippo signaling pathway","volume":"50","author":"Han","year":"2025","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1097\/GME.0000000000000201","article-title":"Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis","volume":"21","author":"Li","year":"2014","journal-title":"Menopause"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"7869","DOI":"10.2147\/IJN.S519945","article-title":"Advances in Functionalized Nanoparticles for Osteoporosis Treatment","volume":"20","author":"Cai","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"172794","DOI":"10.1016\/j.ejphar.2019.172794","article-title":"Icariin promotes osteogenic differentiation by suppressing Notch signaling","volume":"865","author":"Xu","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1124\/dmd.115.064386","article-title":"Intestinal Absorption and Metabolism of Epimedium Flavonoids in Osteoporosis Rats","volume":"43","author":"Zhou","year":"2015","journal-title":"Drug Metab. Dispos."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1142\/S0192415X20500834","article-title":"A Naringin- and Icariin-Contained Herbal Formula, Gushukang, Ameliorated Aged Osteoporosis of Aged Mice with High Calcium Intake","volume":"48","author":"Li","year":"2020","journal-title":"Am. J. Chin. Med."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"124457","DOI":"10.1016\/j.ijpharm.2024.124457","article-title":"Enhancing osteoporosis treatment using a targeted, sustained-release drug delivery system based on macrocyclic amphiphile","volume":"661","author":"Luo","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1186\/s12951-024-02711-1","article-title":"Adipose-derived stem cell exosomes loaded with icariin alleviates rheumatoid arthritis by modulating macrophage polarization in rats","volume":"22","author":"Yan","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"491","DOI":"10.2147\/IJN.S446552","article-title":"Empowering Cartilage Restructuring with Biodegradable Magnesium Doped-Silicon Based-Nanoplatforms: Sustained Delivery and Enhanced Differentiation Potential","volume":"19","author":"Chen","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Gao, J., Gao, J.H., Zhang, Y.F., Gao, D., and Zhang, Y.P. (2026). The multifaceted regulatory effect of icariin on macrophages: A mini-review. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1765533"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"055023","DOI":"10.1088\/1748-605X\/ab9095","article-title":"In vitro effects of the co-release of icariin and strontium from bioactive glass submicron spheres on the reduced osteogenic potential of rat osteoporotic bone marrow mesenchymal stem cells","volume":"15","author":"Mosqueira","year":"2020","journal-title":"Biomed. Mater."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"213856","DOI":"10.1016\/j.bioadv.2024.213856","article-title":"High-strength double-network silk fibroin based hydrogel loaded with Icariin and BMSCs to inhibit osteoclasts and promote osteogenic differentiation to enhance bone repair","volume":"160","author":"Liu","year":"2024","journal-title":"Biomater. Adv."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Zhang, X., Lin, X., Liu, T., Deng, L., Huang, Y., and Liu, Y. (2019). Osteogenic Enhancement Between Icariin and Bone Morphogenetic Protein 2: A Potential Osteogenic Compound for Bone Tissue Engineering. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00201"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"7721","DOI":"10.2147\/IJN.S141052","article-title":"Evaluation of synergistic osteogenesis between icariin and BMP2 through a micro\/meso hierarchical porous delivery system","volume":"12","author":"Wang","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"6019","DOI":"10.2147\/IJN.S203859","article-title":"Icariin-loaded porous scaffolds for bone regeneration through the regulation of the coupling process of osteogenesis and osteoclastic activity","volume":"14","author":"Xie","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s10856-011-4491-4","article-title":"A combined chitosan\/nano-size hydroxyapatite system for the controlled release of icariin","volume":"23","author":"Fan","year":"2012","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Shaukat, A., Shaukat, I., Rajput, S.A., Shukat, R., Hanif, S., Huang, S., Aleem, M.T., Li, K., Li, Q., and Chen, C. (2022). Icariin Alleviates Escherichia coli Lipopolysaccharide-Mediated Endometritis in Mice by Inhibiting Inflammation and Oxidative Stress. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810219"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"e28277","DOI":"10.1097\/MD.0000000000028277","article-title":"Evaluation of the effectiveness and safety of icariin in the treatment of knee osteoarthritis: A protocol for a systematic review and meta-analysis","volume":"100","author":"Liu","year":"2021","journal-title":"Medicine"},{"key":"ref_201","first-page":"191","article-title":"The interlaminar contralateral approach to far-lateral lumbar disc herniations: A single-center comparison with traditional techniques","volume":"67","author":"DI","year":"2023","journal-title":"J. Neurosurg. Sci."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"124","DOI":"10.14715\/cmb\/2017.63.11.22","article-title":"The antiosteoporosis effect of icariin in ovariectomized rats: A systematic review and meta-analysis","volume":"63","author":"Liu","year":"2017","journal-title":"Cell. Mol. Biol."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Pergola, V., Mattesi, G., Cozza, E., Pradegan, N., Tessari, C., Dellino, C.M., Savo, M.T., Amato, F., Cecere, A., and Perazzolo Marra, M. (2023). New Non-Invasive Imaging Technologies in Cardiac Transplant Follow-Up: Acquired Evidence and Future Options. Diagnostics, 13.","DOI":"10.20944\/preprints202306.2206.v1"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"103402","DOI":"10.1016\/j.actpsy.2021.103402","article-title":"A meta-analytic review of the reliability of the Index of Cognitive Activity concerning task-evoked cognitive workload and light influences","volume":"220","author":"Czerniak","year":"2021","journal-title":"Acta Psychol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"713","DOI":"10.31083\/ph.2013.2900","article-title":"A systematic review of the efficacy and pharmacological profile of Herba Epimedii in osteoporosis therapy","volume":"68","author":"Zhai","year":"2013","journal-title":"Pharmazie"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"5814","DOI":"10.62347\/LTGZ9375","article-title":"Osteogenic action of the natural plant material icariin and its potential use in biomedical tissue engineering","volume":"17","author":"Mi","year":"2025","journal-title":"Am. J. Transl. Res."},{"key":"ref_207","first-page":"92","article-title":"Osteoporosis: A Review of Treatment Options","volume":"43","author":"Tu","year":"2018","journal-title":"Pharm. Ther."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Xu, S., Zhao, S., Jian, Y., Shao, X., Han, D., Zhang, F., Liang, C., Liu, W., Fan, J., and Yang, Z. (2022). Icariin-loaded hydrogel with concurrent chondrogenesis and anti-inflammatory properties for promoting cartilage regeneration in a large animal model. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1011260"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"040802","DOI":"10.1116\/6.0004748","article-title":"Emerging biomedical applications of herbal extracts-based biomaterials","volume":"20","author":"Mo","year":"2025","journal-title":"Biointerphases"},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Ilyas, K., Akhtar, M.A., Ammar, E.B., and Boccaccini, A.R. (2022). Surface Modification of 3D-Printed PCL\/BG Composite Scaffolds via Mussel-Inspired Polydopamine and Effective Antibacterial Coatings for Biomedical Applications. Materials, 15.","DOI":"10.3390\/ma15238289"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"e2301604","DOI":"10.1002\/adhm.202301604","article-title":"A Novel PTH-Related Peptide Combined with 3D Printed Macroporous Titanium Alloy Scaffold Enhances Osteoporotic Osseointegration","volume":"12","author":"Wang","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/ame2.12550","article-title":"Pharmacokinetic analysis on compatibility of Atractylodes macrocephala and Paeoniae radix herb pair ameliorates functional constipation model rats using microdialysis with ultra-performance liquid chromatography","volume":"8","author":"Wang","year":"2025","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"100031","DOI":"10.1016\/j.dtrs.2026.100031","article-title":"Necroptosis of stem cell aggregates suppresses bone regeneration via necroptosis-derived extracellular vesicles","volume":"1","author":"Liu","year":"2026","journal-title":"Dent. Res."},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Chilwant, M., Paganini, V., Di Gangi, M., Brignone, S.G., Chetoni, P., Burgalassi, S., Monti, D., and Tampucci, S. (2025). From Sea to Therapy: Marine Biomaterials for Drug Delivery and Wound Healing. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081093"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"8399","DOI":"10.1021\/acsnano.2c02900","article-title":"Near-Infrared Light-Controlled and Real-Time Detection of Osteogenic Differentiation in Mesenchymal Stem Cells by Upconversion Nanoparticles for Osteoporosis Therapy","volume":"16","author":"Yan","year":"2022","journal-title":"ACS Nano"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.actbio.2018.05.005","article-title":"Icariin conjugated hyaluronic acid\/collagen hydrogel for osteochondral interface restoration","volume":"74","author":"Yang","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Xu, Y., Xu, K., Wang, Z., Tang, X., Jiang, Y., and Li, T. (2025). In situ sustained release of icariin from injectable thermosensitive PLGA-PEG-PLGA hydrogels combined with core decompression for steroid-induced osteonecrosis of femoral head. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1643316"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"213848","DOI":"10.1016\/j.bioadv.2024.213848","article-title":"A composite hydrogel loaded with the processed pyritum promotes bone repair via stimulate the osteogenic differentiation of BMSCs","volume":"160","author":"Zhu","year":"2024","journal-title":"Biomater. Adv."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"213958","DOI":"10.1016\/j.bioadv.2024.213958","article-title":"Novel multi-functional microsphere scaffold with shape memory function for bone regeneration","volume":"163","author":"Hu","year":"2024","journal-title":"Biomater. Adv."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"118317","DOI":"10.1016\/j.bmc.2025.118317","article-title":"Icariin modulates the tumor microenvironment in colorectal cancer by targeting M2 macrophage polarization via PI3K\/AKT pathway","volume":"129","author":"Chen","year":"2025","journal-title":"Bioorg Med. Chem."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12951-023-01796-4","article-title":"Turning gray selenium and sublimed sulfur into a nanocomposite to accelerate tissue regeneration by isothermal recrystallization","volume":"21","author":"Cao","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"e2412953","DOI":"10.1002\/advs.202412953","article-title":"Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low-Temperature Photothermal Therapy via Targeting HSP90-TXNDC9 Interactions","volume":"12","author":"He","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Sobrino, R., Casado-Losada, I., Caltagirone, C., Garc\u00eda-Crespo, A., Garc\u00eda, C., Rodr\u00edguez-Hern\u00e1ndez, J., Reinecke, H., Gallardo, A., Elvira, C., and Mart\u00ednez-Campos, E. (2024). Osteoblastic Cell Sheet Engineering Using P(VCL-HEMA)-Based Thermosensitive Hydrogels Doped with pVCL@Icariin Nanoparticles Obtained with Supercritical CO2-SAS. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16081063"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/s12951-023-02124-6","article-title":"An injectable and thermosensitive hydrogel with nano-aided NIR-II phototherapeutic and chemical effects for periodontal antibacteria and bone regeneration","volume":"21","author":"Wang","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_225","doi-asserted-by":"crossref","unstructured":"Xie, L., Liu, N., Xiao, Y., Liu, Y., Yan, C., Wang, G., and Jing, X. (2020). In Vitro and In Vivo Osteogenesis Induced by Icariin and Bone Morphogenetic Protein-2: A Dynamic Observation. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01058"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"0090","DOI":"10.34133\/bmr.0090","article-title":"Repair of Osteoporotic Bone Defects in Rats via the Sirtuin 1-Wnt\/\u03b2-catenin Signaling Pathway by Novel Icariin\/Porous Magnesium Alloy Scaffolds","volume":"28","author":"Yu","year":"2024","journal-title":"Biomater. Res."},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Li, P., Xu, T.Y., Yu, A.X., Liang, J.L., Zhou, Y.S., Sun, H.Z., Dai, Y.L., Liu, J., and Yu, P. (2025). The Role of Ferroptosis in Osteoporosis and Advances in Chinese Herbal Interventions. Biology, 14.","DOI":"10.3390\/biology14040367"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"113085","DOI":"10.1016\/j.yexcr.2022.113085","article-title":"Icariin triggers osteogenic differentiation of bone marrow stem cells by up-regulating miR-335-5p","volume":"414","author":"Teng","year":"2022","journal-title":"Exp. Cell Res."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/21691401.2025.2490677","article-title":"Enhanced cartilage repair using gelatin methacryloyl hydrogels combined with icariin and magnesium-doped bioactive glass","volume":"53","author":"Liao","year":"2025","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"055018","DOI":"10.1088\/2057-1976\/adf8ee","article-title":"Study on the effect of sustained -release icariin-loaded Graphene oxide-hydrogel composite scaffold on bone defect repair","volume":"11","author":"Qu","year":"2025","journal-title":"Biomed. Phys. Eng. Express"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"131169","DOI":"10.1016\/j.ijbiomac.2024.131169","article-title":"Functionalized chitosan hydrogel promotes osseointegration at the interface of3D printed titanium alloy scaffolds","volume":"266","author":"Zhu","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"100025","DOI":"10.1016\/j.dtrs.2026.100025","article-title":"Notch signalling in alveolar bone development and regeneration: A critical regulator for osteoblasts to osteocytes transitioning","volume":"1","author":"Cai","year":"2026","journal-title":"Dent. Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/10\/935\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:21:40Z","timestamp":1779697300000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/10\/935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":232,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cells15100935"],"URL":"https:\/\/doi.org\/10.3390\/cells15100935","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]}}}