School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
J Chromatogr A. 2024 Nov 22;1737:465465. doi: 10.1016/j.chroma.2024.465465. Epub 2024 Oct 22.
Terminalia bellirica (Gaertn.) Roxb. is an ethnomedicinal plant that has been utilized in Tibetan and traditional Chinese medicine (TCM). Nevertheless, its quality standard officially listed in the Chinese Pharmacopoeia does not include any content determination of the indicator components of Terminaliae Belliricae Fructus, which constrains the effective quality evaluation of medicinal material and related products. In this paper, a three-dimensional "content-pharmacokinetics-pharmacology" network strategy was developed to identify the quality markers (Q-markers) of Terminaliae Belliricae Fructus in terms of "measurability", "traceability" and "effectiveness". Chromatographic fingerprint analysis was performed to outline its chemical contour, and identify the differential components of 17 batches of Terminaliae Belliricae Fructus combined with multivariate statistics analysis and UPLC-QTOF-MS analysis. Serum pharmacochemistry analysis was implemented on rats, and 25 prototype components absorbed into the blood were identified. By network pharmacology analysis, a component-disease-target-pathway network was constructed, thus validating the effectiveness of the chemical components of Terminaliae Belliricae Fructus. Afterwards, the above screened candidate components were put into construction of three-dimensional "radar chart". According to the calculated regression area (RA) and coefficient of variation (CV) values, the potential Q-markers was determined, followed by "specificity" evaluation. Ultimately, ellagic acid (EA), chebulagic acid (CHA), gallic acid (GA), chebulinic acid (CA), corilagin (CO) and chebulanin (CH) were specified as the Q-markers of Terminaliae Belliricae Fructus. Owing to high content, good pharmacokinetic property, high pharmacological activities and specificity. The screened Q-markers could offer a scientific foundation for the quality control of Terminaliae Belliricae Fructus, and the proposed strategy is demonstrated to be reliable and feasible for deciphering Q-markers of TCM.
诃子（Terminalia bellirica（Gaertn.）Roxb.）是一种民族药用植物，已被用于藏药和中药（TCM）。然而，其在中国药典中正式列出的质量标准不包括对诃子果实指标成分的任何含量测定，这限制了药材和相关产品的有效质量评价。在本文中，开发了一个三维的“含量-药代动力学-药理学”网络策略，以确定诃子的质量标志物（Q-标志物），从“可测量性”、“可追溯性”和“有效性”三个方面进行考量。通过色谱指纹图谱分析勾勒其化学轮廓，并结合多元统计分析和 UPLC-QTOF-MS 分析，确定了 17 批诃子果实的差异成分。对大鼠进行血清药代化学分析，鉴定出 25 个原型成分被吸收到血液中。通过网络药理学分析，构建了一个成分-疾病-靶标-通路网络，从而验证了诃子果实化学成分的有效性。之后，将上述筛选出的候选成分纳入三维“雷达图”的构建。根据计算出的回归面积（RA）和变异系数（CV）值，确定潜在的 Q-标志物，并进行“特异性”评价。最终，确定鞣花酸（EA）、诃黎勒酸（CHA）、没食子酸（GA）、诃子酸（CA）、柯里拉京（CO）和诃子宁（CH）为诃子的 Q-标志物。由于含量高、药代动力学性质好、药理活性高、特异性好。筛选出的 Q-标志物可为诃子的质量控制提供科学依据，所提出的策略被证明是可靠和可行的，可用于破译中药的 Q-标志物。
