Hulea Calin, Obistioiu Diana, Hulea Anca, Suleiman Mukhtar Adeiza, Floares Oarga Doris, Alexa Ersilia, Imbrea Ilinca Merima, Neacșu Alina-Georgeta, Pentea Marius, Popescu Cosmin Alin, Imbrea Florin
Faculty of Veterinary Medicine, University of Life Sciences "King Michael I" from Timisoara, Calea Aradului 119, 300645 Timisoara, Romania.
Faculty of Agriculture, University of Life Sciences "King Michael I" from Timisoara, Calea Aradului 119, 300645 Timisoara, Romania.
Antibiotics (Basel). 2025 Jun 8;14(6):592. doi: 10.3390/antibiotics14060592.
This study evaluated the polyphenolic composition, antibacterial activity, molecular docking interactions, and pharmacokinetic properties of Romanian oak and fir honeydew honeys. Spectrophotometric methods quantified total phenolic, flavonoid contents and antioxidant activity, and individual polyphenols were identified via HPLC-MS. Antibacterial efficacy against Gram-positive and Gram-negative bacteria was evaluated by determining the bacterial inhibition percentage and minimum inhibitory concentrations. The bioactive compounds identified via LC-MS analysis were used to further delineate the possible antibacterial activities in silico. Molecular docking was carried out to predict the binding interactions and complex formation of the identified compounds against protein crystal structures of the bacteria used in this study. Additionally, the pharmacokinetic profile of compounds with high inhibitory potential was assessed via ADMET (absorption, Distribution, Metabolism, Excretion, toxicity) predictors to ascertain their value. Fir honeydew honey showed higher total phenolic (844.5 mg GAE/kg) and flavonoid contents (489.01 mg QUE/kg) compared to oak honeydew honey, correlating with more potent antioxidant activity (IC50 = 5.16 mg/mL). In vitro antimicrobial tests indicated a stronger inhibitory effect of fir honeydew honey, especially against Gram-positive strains like , , and , alongside certain Gram-negative strains such as and . Oak honeydew honey displayed selective antimicrobial action, particularly against and . The docking outcomes showed rutin, rosmarinic acid, beta resorcylic acid, quercetin, ferulic acid, and p-coumaric acid have high inhibitory activities characterised by binding affinities and binding interactions against shiga toxin, riboflavin synthase, ATP-binding sugar transporter-like protein, undecaprenyl diphosphate synthase, putative lipoprotein, sortase A, and immunity protein, making them key contributors to the honey's antimicrobial activity. Moreover, beta-resorcylic acid, quercetin, ferulic acid, and p-coumaric acid revealed interesting ADMET scores that qualify honey to serve as a good antimicrobial agent. These findings support their potential use as natural antibacterial agents and emphasise the value of integrating chemical, biological, and computational approaches for multidisciplinary characterisations.
本研究评估了罗马尼亚橡木蜜露蜂蜜和冷杉蜜露蜂蜜的多酚成分、抗菌活性、分子对接相互作用和药代动力学特性。采用分光光度法对总酚、黄酮含量及抗氧化活性进行定量分析，并通过高效液相色谱 - 质谱联用（HPLC-MS）鉴定单个多酚。通过测定细菌抑制率和最低抑菌浓度来评估对革兰氏阳性菌和革兰氏阴性菌的抗菌效果。通过液相色谱 - 质谱分析鉴定出的生物活性化合物被用于进一步在计算机模拟中描绘可能的抗菌活性。进行分子对接以预测所鉴定化合物与本研究中使用的细菌蛋白质晶体结构的结合相互作用和复合物形成。此外，通过ADMET（吸收、分布、代谢、排泄、毒性）预测器评估具有高抑制潜力的化合物的药代动力学特征，以确定它们的价值。与橡木蜜露蜂蜜相比，冷杉蜜露蜂蜜显示出更高的总酚含量（844.5毫克没食子酸当量/千克）和黄酮含量（489.01毫克槲皮素当量/千克），这与更强的抗氧化活性（IC50 = 5.16毫克/毫升）相关。体外抗菌试验表明，冷杉蜜露蜂蜜具有更强的抑制作用，尤其是对诸如、和等革兰氏阳性菌株以及某些革兰氏阴性菌株如和。橡木蜜露蜂蜜表现出选择性抗菌作用，特别是对和。对接结果表明，芦丁、迷迭香酸、β - 间苯二酚酸、槲皮素、阿魏酸和对香豆酸具有高抑制活性，其特征在于与志贺毒素、核黄素合酶、ATP结合糖转运样蛋白、十一异戊烯二磷酸合酶、假定脂蛋白、分选酶A和免疫蛋白的结合亲和力和结合相互作用，使其成为蜂蜜抗菌活性的关键贡献者。此外，β - 间苯二酚酸、槲皮素、阿魏酸和对香豆酸显示出有趣的ADMET评分，这使蜂蜜有资格作为一种良好的抗菌剂。这些发现支持了它们作为天然抗菌剂的潜在用途，并强调了整合化学、生物学和计算方法进行多学科表征的价值。
