{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:49:14Z","timestamp":1782485354639,"version":"3.54.5"},"reference-count":79,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Saponarin, a flavonoid glycoside, has demonstrated various pharmacological effects in preclinical systems, including antioxidant, anti\u2010inflammatory, hepatoprotective, neuroprotective, anticancer, and cardioprotective properties. These effects are attributed to its modulation of key signaling pathways such as Nrf2, NF\u2010\u03baB, PI3K\/Akt, MAPK, and TGF\u2010\u03b2. However, the translational relevance of these interactions remains unestablished in human subjects. This review consolidates findings on saponarin's mechanisms of action and therapeutic potential, focusing primarily on in\u00a0vitro and animal model evidence, while highlighting gaps that limit its clinical applicability across liver diseases, neurodegenerative conditions, cancer, diabetes, and cardiovascular diseases. In hepatic disease models, saponarin has shown potential in reducing oxidative stress markers, attenuating liver fibrosis, and improving mitochondrial function, indicating its relevance to non\u2010alcoholic fatty liver disease, alcoholic liver disease, and drug\u2010induced liver injury. However, these findings have not been confirmed in human trials, and the translation of rodent hepatoprotective data to humans remains uncertain. In neurodegenerative models, saponarin reduced \u03b2\u2010amyloid deposition and tau hyperphosphorylation. However, poor blood\u2013brain barrier penetration and the lack of human validation limit the therapeutic relevance for Alzheimer's and Parkinson's diseases. In cancer models, saponarin inhibited proliferation, induced apoptosis, suppressed metastatic markers, and reduced angiogenic signaling. However, cancer cell line sensitivity often fails to predict in\u00a0vivo efficacy, and no clinical evidence supports its use as adjunctive cancer therapy. Limited preclinical evidence also suggests potential effects on insulin sensitivity, glycemic regulation, and cardiovascular parameters, but human studies are absent. Despite these promising findings, saponarin lacks clinical validation. Most effects come from in\u00a0vitro and animal models, which exhibit variability in experimental conditions, doses, and formulations, limiting definitive conclusions. Saponarin's poor oral bioavailability, absence of standardized formulations, restricted blood\u2013brain barrier penetration, and lack of long\u2010term safety data present significant barriers to development. Although novel delivery methods such as nanoparticles and liposomal formulations have been proposed to improve pharmacokinetics, they remain experimental and unvalidated in humans. Future research should focus on rigorous clinical trials to assess whether preclinical findings translate to clinically meaningful outcomes, alongside comprehensive pharmacokinetic and safety evaluations in humans. Until then, saponarin should be regarded as an experimental compound with preliminary preclinical findings, rather than a clinically recommended therapeutic agent.<\/jats:p>","DOI":"10.1111\/cbdd.70339","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T10:41:13Z","timestamp":1781347273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Saponarin: Therapeutic Potential, Pharmacological Insights, and Future Directions"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-2212","authenticated-orcid":false,"given":"Mohammed A.","family":"Abdel\u2010Rasol","sequence":"first","affiliation":[{"name":"Department of Zoology, Faculty of Science Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3622-1417","authenticated-orcid":false,"given":"Wael M.","family":"El\u2010Sayed","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science Ain Shams University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c00817"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119746843.ch9"},{"key":"e_1_2_16_4_1","first-page":"337","volume-title":"Functional Foods and Nutraceuticals: Bioactive Components, Formulations and Innovations","author":"Adetunji C. 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