Fuente: PubMed "honey" Food Sci Nutr. 2026 Jun 17;14(6):e72021. doi: 10.1002/fsn3.72021. eCollection 2026 Jun.ABSTRACTHoney is a natural sweet substance produced by bees from nectar and plant secretions, which is abundant in nutrients and exhibits excellent biological activities. However, owing to deficiencies in the quality control index system, prominent issues such as honey adulteration and improper processing are prevalent in the current market, resulting in a severe decline in honey quality. Therefore, this study focuses on acacia honey, one of the four major honey varieties in China, by screening its characteristic components and analyzing the correlation between these components and immunomodulatory activity, aiming to provide targeted theoretical basis and indicator support for resolving the aforementioned practical issues. The results demonstrated that natural acacia honey (NAH) had significant advantages over commercial acacia honey (CAH) in key quality indices (total flavonoids, total phenols, proline content, amylase activity, etc.) and quality consistency, with significantly higher immunomodulatory activity. Combined with machine learning and chemometric analyses, hesperetin and pinocembrin were confirmed as the characteristic components of NAH from the 50 components identified via ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry (UPLC-QE-MS) analysis. In vitro experiments demonstrated that both components at 50 μM effectively promoted mouse splenic lymphocyte proliferation, reduced NO and TNF-α secretion in LPS-induced RAW264.7 macrophages, and showed no obvious cytotoxicity, indicating their potential as characteristic markers for evaluating NAH quality and functional activity. Further network pharmacology and molecular docking studies indicated that hesperetin and pinocembrin could mediate immunomodulatory effects by regulating 10 core targets including MMP9, MMP2, BCL2, and SRC, as well as the PI3K-AKT pathway, with the markers showing the strongest binding activity toward MMP2. This study established a characteristic marker identification system for NAH, and provided scientific indicator support for formulating acacia honey quality standards and improvement of processing technologies.PMID:42317499 | PMC:PMC13273532 | DOI:10.1002/fsn3.72021