红花注射液(SI),从红花(红花L.)中提取的水提取物制剂,已广泛用于心脑血管疾病的治疗。这项工作旨在开发一种使用SI作为案例研究来识别心血管草药PK标记的方法。首先,通过HPLC-MS进行定性和定量分析以揭示制剂的成分。随后,进行了多种PK成分和综合PK调查,以确定具有有利PK特性的成分(例如,易于在常规PK时间点和高系统暴露下检测到),用于整个制剂。接下来,通过目标捕捞和系统药理学研究,预测了制剂中针对心血管疾病(CVD)的成分。最后,具有良好PK特性的成分,令人满意的PK代表性的准备,与CVD高度相关被认为是潜在的PK标记。使用H2O2诱导的H9c2心肌细胞损伤模型和蛋白质组学研究进一步评估其治疗效果以鉴定客观PK标记。作为结果,它披露SI主要包含11种成分。其中,五种成分,即,羟基红花黄色素A(HSYA),注射器(SYR),对香豆酸(p-CA),scutellarin(SCU),和对羟基苯甲醛(p-HBA),表现出良好的PK性能。HSYA,SYR,和芦丁(RU)预测显示与CVD高度相关,并筛选为潜在的PK标记。然而,只有HSYA和SYR被确认为抗CVD的治疗成分.结合这些发现,只有HSYA在制剂的多种成分的PK特性和治疗效果方面表现出令人满意的代表性,从而表明HSYA是SI的潜在PK标记。本研究结果可为中药PK标志物的表征提供参考。
Safflower injection (SI), a water-extract preparation from safflower (Carthamus tinctorius L.), has been widely used for the treatment of cardio-cerebrovascular diseases. This work aims to develop an approach for identifying PK markers of cardiovascular herbal medicines using SI as a case
study. Firstly, qualitative and quantitative analyses were performed to reveal ingredients of the preparation via HPLC-MS. Subsequently, multiple PK ingredients and integrated PK investigations were carried out to ascertain ingredients with favorable PK properties (e.g., easily detected at conventional PK time points and high system exposure) for the whole preparation. Next, ingredients against cardiovascular diseases (CVDs) in the preparation were predicted with target fishing and system pharmacology studies. Finally, ingredients with favorable PK properties, satisfactory PK representativeness for the preparation, and high relevance to CVDs were considered as potential PK markers. Their therapeutic effect was further evaluated using the H2O2-induced H9c2 cardiomyocyte-injured model and a proteomics
study to identify objective PK markers. As results, it disclosed that SI mainly contains 11 ingredients. Among them, five ingredients, namely, hydroxysafflor yellow A (HSYA), syringin (SYR), p-coumaric acid (p-CA), scutellarin (SCU), and p-hydroxybenzaldehyde (p-HBA), showed favorable PK properties. HSYA, SYR, and rutin (RU) were predicted to show high relevance to CVDs and screened as potential PK markers. However, only HSYA and SYR were confirmed as therapeutic ingredients against CVDs. Combined with these findings, only HSYA demonstrated satisfactory representativeness on PK properties and therapeutic effects of multiple ingredients of the preparation, thereby indicating that HSYA is a potential PK marker for the SI. The results of this
study can provide a reference for the characterization of PK markers for traditional Chinese medicines.