Shah Abdul Bari, Baiseitova Aizhamal, Kim Jeong Ho, Lee Yong Hyun, Park Ki Hun
Division of Applied Life Science (BK21 plus), IALS, Gyeongsang National University, Jinju, Korea.
Front Pharmacol. 2022 May 11;13:890649. doi: 10.3389/fphar.2022.890649. eCollection 2022.
Bacterial neuraminidase (BNA) plays a pivotal role in the pathogenesis of several microbial diseases including biofilm formation. The aim of this study is to reveal the neuraminidase inhibitory potential of metabolites from (L.) Hook. which have diverse biological activities including PTP1B and -glucosidase. The six ugonins () from the target plant showed significant neuraminidase inhibition. The inhibitory potencies were observed at a nanomolar level of 35-50 nM, which means they are 100 times more active than their corresponding mother compounds (eriodyctiol and luteolin). A detailed kinetic study revealed that all ugonins were reversible noncompetitive inhibitors. An in-depth investigation of the most potent compound showed its time-dependent inhibition with the isomerization model having = 0.0103 min, = 0.0486 min, and = 0.062 μM. The binding affinities ( ) were agreed closely with our prediction based on the inhibitory potencies. Particularly, ugonin J () blocked the biofilm formation of dose-dependently up to 150 µM without the inhibition of bacteria. The major compounds () in the extract were characterized by UPLC-ESI-Q-TOF/MS.
细菌神经氨酸酶（BNA）在包括生物膜形成在内的多种微生物疾病的发病机制中起关键作用。本研究的目的是揭示来自毛钩藤（L.）Hook.的具有多种生物活性（包括对蛋白酪氨酸磷酸酶1B和β-葡萄糖苷酶的活性）的代谢产物的神经氨酸酶抑制潜力。目标植物中的六种钩藤苷元表现出显著的神经氨酸酶抑制作用。在35 - 50 nM的纳摩尔水平观察到抑制效力，这意味着它们的活性比其相应的母体化合物（圣草酚和木犀草素）高100倍。详细的动力学研究表明，所有钩藤苷元都是可逆的非竞争性抑制剂。对最有效的化合物进行深入研究表明其具有时间依赖性抑制作用，异构化模型的参数为k₁ = 0.0103 min⁻¹，k₂ = 0.0486 min⁻¹，K₁ = 0.062 μM。结合亲和力（K₁）与基于抑制效力的预测结果非常吻合。特别是，钩藤苷J在高达150 μM的剂量下剂量依赖性地阻断了金黄色葡萄球菌的生物膜形成，且不抑制细菌生长。提取物中的主要化合物通过超高效液相色谱 - 电喷雾 - 四级杆 - 飞行时间质谱（UPLC - ESI - Q - TOF/MS）进行了表征。
