Tianjin State Key Laboratory of Modern Chinese Medicine, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Tianjin State Key Laboratory of Modern Chinese Medicine, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Sep 1;1229:123898. doi: 10.1016/j.jchromb.2023.123898. Epub 2023 Sep 26.
Fructus Psoraleae (FP), one of the important traditional Chinese medicines, is widely used in clinic and has been reported to be hepatotoxic. However, there is no report on the mechanism of FP-induced hepatotoxicity based on the theory of You Gu Wu Yun. In this study, plasma samples of rats with different kidney deficiency syndromes were investigated using a lipidomics approach based on UPLC/Q-TOF-MS technique. Firstly, multivariate statistical analysis, VIP value test, statistical test and other methods were used to find the lipid metabolites in the two syndrome model groups that were different from the normal group. The screening of differential lipid metabolites revealed that there were 12 biomarkers between the blank group and the kidney-yang deficiency model group as well as 16 differential metabolites between the kidney-yin deficiency model group, and finally a total of 17 relevant endogenous metabolites were identified, which could be used as differential lipid metabolites to distinguish between kidney-yin deficiency and kidney-yang deficiency evidence. Secondly, the relative content changes of metabolites in rats after administration of FP decoction were further compared to find the substances associated with toxicity after administration, and the diagnostic ability of the identified biomarkers was evaluated using a receiver operating characteristic curve (ROC). Results a total of 14 potential differential lipid metabolites, including LysoPC(20:0/0:0) and LysoPC(16:0/0:0), which may be related to hepatotoxicity in rats with kidney-yin deficiency syndrome were further screened, namely, the potential active lipid metabolites related to hepatotoxicity in rats induced by FP. Finally, cluster analysis, MetPA analysis and KEGG database were used to analyze metabolic pathways. It was discovered that the metabolism of glycerophospholipid and sphingolipid may be strongly related to the mechanism of hepatotoxicity brought on by FP. Overall, we described the lipidomics changes in rats treated with FP decoction and screened out 14 lipid metabolites related to hepatotoxicity in rats with kidney-yin deficiency, which served as a foundation for the theory of "syndrome differentiation and treatment" in traditional Chinese medicine and a guide for further investigation into the subsequent mechanism.
补骨脂（FP）是一种重要的中药，广泛应用于临床，已有报道称其具有肝毒性。然而，基于“以药测证”理论，目前尚无 FP 诱导肝毒性的机制研究报道。本研究采用基于 UPLC/Q-TOF-MS 技术的脂质组学方法，对不同肾虚证型大鼠的血浆样本进行了研究。首先，采用多元统计分析、VIP 值检验、统计检验等方法，寻找两种证型模型组与正常组之间差异的脂质代谢物。差异脂质代谢物的筛选发现，肾阳虚证模型组与空白组之间有 12 个生物标志物，肾阴虚证模型组与空白组之间有 16 个差异代谢物，最终共鉴定出 17 个相关内源性代谢物，可作为区分肾阴虚证和肾阳虚证的差异脂质代谢物。其次，进一步比较 FP 汤给药后大鼠代谢物的相对含量变化，寻找与毒性相关的物质，并采用受试者工作特征曲线（ROC）评价鉴定生物标志物的诊断能力。结果共筛选出 14 种潜在的差异脂质代谢物，包括 LysoPC（20：0/0：0）和 LysoPC（16：0/0：0），可能与肾阴虚证大鼠的肝毒性有关，即 FP 引起肾阴虚证大鼠肝毒性的潜在活性脂质代谢物。最后，采用聚类分析、MetPA 分析和 KEGG 数据库对代谢通路进行分析。发现甘油磷脂和鞘脂代谢可能与 FP 引起的肝毒性机制密切相关。总之，本研究描述了 FP 汤给药后大鼠的脂质组学变化，筛选出与肾阴虚证大鼠肝毒性相关的 14 种脂质代谢物，为中药“辨证论治”理论提供了依据，并为后续机制研究提供了指导。
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