Chen Jiayun, Jiang Xiaojuan, Zhu Chunyan, Yang Lu, Liu Minting, Zhu Mingshe, Wu Caisheng
Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
College of Pharmacy, Jiamusi University, Jiamusi, China.
Front Pharmacol. 2022 Mar 21;13:865066. doi: 10.3389/fphar.2022.865066. eCollection 2022.
Rhubarb, as a traditional Chinese medicine, has several positive therapeutic effects, such as purging and attacking accumulation, clearing heat and purging fire, cooling blood, and detoxification. Recently, Rhubarb has been used in prescriptions for the prevention and treatment of COVID-19, with good efficacy. However, the exploration of effective quantitative approach to ensure the consistency of rhubarb's therapeutic efficacy remains a challenge. In this case, this study aims to use non-targeted and targeted data mining technologies for its exploration and has comprehensively identified 72 rhubarb-related components in human plasma for the first time. In details, the area under the time-concentration curve (AUC)-pooled method was used to quickly screen the components with high exposure, and the main components were analyzed using Pearson correlation and other statistical analyses. Interestingly, the prototype component (rhein) with high exposure could be selected out as a Q-marker, which could also reflect the metabolic status changes of rhubarb anthraquinone in human. Furthermore, after comparing the metabolism of different species, mice were selected as model animals to verify the pharmacodynamics of rhein. The experimental results showed that rhein has a positive therapeutic effect on pneumonia, significantly reducing the concentration of pro-inflammatory factors [interleukin (IL)-6 and IL-1β] and improving lung disease. In short, based on the perspective of human exposure, this study comprehensively used intelligent data post-processing technologies and the AUC-pooled method to establish that rhein can be chosen as a Q-marker for rhubarb, whose content needs to be monitored individually.
大黄作为一种传统中药，具有多种积极的治疗作用，如泻下攻积、清热泻火、凉血解毒等。近年来，大黄已被用于防治新型冠状病毒肺炎的方剂中，疗效良好。然而，探索有效的定量方法以确保大黄治疗效果的一致性仍然是一个挑战。在此情况下，本研究旨在利用非靶向和靶向数据挖掘技术进行探索，并首次在人血浆中全面鉴定出72种与大黄相关的成分。具体而言，采用时间-浓度曲线下面积（AUC）合并法快速筛选高暴露成分，并使用Pearson相关性分析等统计方法对主要成分进行分析。有趣的是，高暴露的原型成分（大黄酸）可被选为Q-标志物，其也能反映大黄蒽醌在人体内的代谢状态变化。此外，在比较不同物种的代谢情况后，选择小鼠作为模型动物来验证大黄酸的药效学。实验结果表明，大黄酸对肺炎具有积极的治疗作用，可显著降低促炎因子[白细胞介素（IL）-6和IL-1β]的浓度并改善肺部疾病。简而言之，本研究从人体暴露的角度出发，综合运用智能数据后处理技术和AUC合并法，确定大黄酸可被选为大黄的Q-标志物，其含量需要进行个体化监测。
