Chen Bing, Luo Hongbin, Chen Weiying, Huang Qishu, Zheng Kaifan, Xu Dafen, Li Shaoguang, Liu Ailin, Huang Liying, Zheng Yanjie, Lin Xinhua, Yao Hong
Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), School of Pharmacy, Nano Medical Technology Research Institute, Fujian Medical University, Fuzhou, China.
Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, China.
Front Pharmacol. 2021 Nov 17;12:761884. doi: 10.3389/fphar.2021.761884. eCollection 2021.
Delicaflavone (DF), a natural active ingredient from Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated the pharmacokinetic profile of DF in rats using a validated HPLC-MS/MS methods, as well as its human serum albumin (HSA) binding properties through multi-spectroscopic and methods. The results showed that DF was rapidly eliminated and had a widespread tissue distribution after intravenous administration. DF showed linear dynamics in the dose range of 30-60 mg/kg and poor oral bioavailability. The major distribution tissues of DF were the liver, lungs, and kidneys. Ultraviolet and fluorescence spectroscopy and molecular docking demonstrated that DF had a static quenching effect on HSA, with one binding site, and relatively strong binding constants. Thermodynamic analysis of the binding data revealed that hydrogen bonding and van der Waals interactions played major roles in binding. The results of this study further our understanding of the pharmacokinetic and plasma protein binding properties of the potential anticancer agent DF and shed light on pharmacological strategies that may be useful for the development of novel cancer therapeutics.
地锦草黄酮（DF）是一种从地锦草中提取的天然活性成分，据报道具有良好的抗癌作用，因此被认为是一种潜在的抗癌药物。然而，其药代动力学和血浆蛋白结合特性尚不清楚。在此，我们使用经过验证的高效液相色谱-串联质谱法研究了DF在大鼠体内的药代动力学特征，并通过多种光谱法研究了其与人血清白蛋白（HSA）的结合特性。结果表明，静脉给药后，DF被迅速清除，组织分布广泛。DF在30-60mg/kg剂量范围内呈现线性动力学，口服生物利用度较差。DF的主要分布组织为肝脏、肺和肾脏。紫外和荧光光谱以及分子对接表明，DF对HSA具有静态猝灭作用，有一个结合位点，且结合常数相对较强。结合数据的热力学分析表明，氢键和范德华相互作用在结合中起主要作用。本研究结果进一步加深了我们对潜在抗癌药物DF的药代动力学和血浆蛋白结合特性的理解，并为可能有助于开发新型癌症治疗药物的药理策略提供了线索。
