Fuente: PubMed "propolis" World J Exp Med. 2025 Dec 20;15(4):110482. doi: 10.5493/wjem.v15.i4.110482. eCollection 2025 Dec 20.ABSTRACTPinocembrin (PB) (5,7-dihydroxy flavanone) is a naturally occurring flavonoid sourced from propolis and Pinus spp., with the formula C15H12O4 and moderate lipophilicity (log P approximately 2.1-2.5), which underlies both its bioactivity and formulation challenges. In rodents, oral administration yields rapid absorption but extensive first-pass glucuronidation and sulfation, resulting in conjugates that dominate plasma, limit bioavailability (< 10%) and confer a short half-life. In vitro, PB induces intrinsic mitochondrial apoptosis, downregulating Bcl-2, upregulating Bax, promoting cytochrome C release, and activating caspases-9/caspases-3 while inhibiting phosphoinositol-3 kinase/protein kinase B and STAT3 signaling, arresting cell-cycle progression, and suppressing metastatic markers (matrix metalloproteinase-9, vascular endothelial growth factor) across several cancer cell lines. Corresponding in vivo xenograft and orthotopic models demonstrate significant tumor growth inhibition, decreased Ki-67 indices, and increased cleaved caspase-3 without overt toxicity. To address solubility and clearance, MPEG-PDLLA micelles increased oral bioavailability by 5.3-fold and extended the half-life from 1.2 hours to 2.6 hours, while D-α-tocopheryl polyethylene glycol 1000 succinate liposomes achieved a 1.9-fold bioavailability increase and prolonged the half-life to 14.2 hours, indicating substantial pharmacokinetic (PK) enhancement and sustained systemic exposure in rodents. Toxicology studies report a no-observed-adverse-effect level ≥ 500 mg/kg in rats with no mutagenicity, and phase I trials (0.5-10 mg/kg) confirm human tolerability. Key gaps remain in target validation, long-term toxicity, and prodrug development. This review is novel in its integration of pharmacology, formulation advances, safety assessments, and translational considerations for PB. To our knowledge, it is the first to systematically compare multiple nanocarrier systems in terms of their ability to improve oral bioavailability and PK parameters of PB.PMID:41497679 | PMC:PMC12767260 | DOI:10.5493/wjem.v15.i4.110482