Jeličić Mario-Livio, Amidžić Klarić Daniela, Kovačić Jelena, Verbanac Donatella, Mornar Ana
Department of Pharmaceutical Analysis, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia.
Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia.
Pharmaceuticals (Basel). 2022 Aug 4;15(8):965. doi: 10.3390/ph15080965.
In the present study, various procedures have been compared for the determination of lipophilicity, hydrophobicity, and plasma protein binding of curcuminoids, boswellic acids, andrographolides, and piperine as biologically active ingredients of botanicals used in IBD treatment. Our results have shown that IAM-HPLC assay is the most suitable one for lipophilicity determination of all analytes regardless of their class and botanical source. HSA-HPAC and AGP-HPAC assays revealed that all investigated compounds have a higher affinity for HSA which is the most abundant protein in human plasma. The high affinity of biologically active compounds to all biological structures (phospholipids and proteins) admonishes that their small portion is available for therapeutic effects in IBD patients. Our experimental research is complemented by various theoretical approaches based on different algorithms for pharmacokinetic properties prediction. The similarities between experimental and calculated values were evaluated using PCA and CA as a statistical tool. The statistical analysis implies that plasma protein binding is a complex process, and theoretical approaches still cannot fully replace experimental ones.
在本研究中,对用于测定姜黄素类、乳香酸、穿心莲内酯和胡椒碱(作为用于治疗炎症性肠病的植物药的生物活性成分)的亲脂性、疏水性和血浆蛋白结合的各种方法进行了比较。我们的结果表明,无论分析物的类别和植物来源如何,IAM-HPLC测定法都是测定所有分析物亲脂性的最合适方法。HSA-HPAC和AGP-HPAC测定法表明,所有研究的化合物对人血浆中最丰富的蛋白质HSA具有更高的亲和力。生物活性化合物对所有生物结构(磷脂和蛋白质)的高亲和力表明,它们的一小部分可用于炎症性肠病患者的治疗效果。我们的实验研究通过基于不同算法的各种理论方法进行补充,以预测药代动力学性质。使用主成分分析(PCA)和聚类分析(CA)作为统计工具评估实验值和计算值之间的相似性。统计分析表明,血浆蛋白结合是一个复杂的过程,理论方法仍不能完全取代实验方法。