Yu Yingli, Wang Pengli, Yu Ruili, Lu Jiaxi, Jiang Miaomiao, Zhou Kun
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Tianjin Key Laboratory of Chinese medicine Pharmacology, Tianjin 300193, China.
Metabolites. 2019 Nov 2;9(11):263. doi: 10.3390/metabo9110263.
Pre-clinical safety evaluation of traditional medicines is imperative because of the universality of drug-induced adverse reactions. Psoralen and isopsoralen are the major active molecules and quality-control components of a traditional herbal medicine which is popularly used in Asia, . The purpose of this study is to assess the long-term effects of psoralen and isopsoralen with low levels on the biochemical parameters and metabolic profiles of rats. Three doses (14, 28, and 56 mg/kg) of psoralen and one dose (28 mg/kg) of isopsoralen were administered to rats over 12 weeks. Blood and selected tissue samples were collected and analyzed for hematology, serum biochemistry, and histopathology. Metabolic changes in serum samples were detected via proton nuclear magnetic resonance (H-NMR) spectroscopy. We found that psoralen significantly changed the visceral coefficients, blood biochemical parameters, and histopathology, and isopsoralen extra influenced the hematological index. Moreover, psoralen induced remarkable elevations of forvaline, isoleucine, isobutyrate, alanine, acetone, pyruvate, glutamine, citrate, unsaturated lipids, choline, creatine, phenylalanine, and 4-hydroxybenzoate, and significant reductions of ethanol and dimethyl sulfone. Isopsoralen only induced a few remarkable changes of metabolites. These results suggest that chronic exposure to low-level of psoralen causes a disturbance in alanine metabolism, glutamate metabolism, urea cycle, glucose-alanine cycle, ammonia recycling, glycine, and serine metabolism pathways. Psoralen and isopsoralen showed different toxicity characteristics to the rats.
由于药物不良反应的普遍性，传统药物的临床前安全性评估势在必行。补骨脂素和异补骨脂素是一种在亚洲广泛使用的传统草药的主要活性分子和质量控制成分。本研究的目的是评估低剂量补骨脂素和异补骨脂素对大鼠生化参数和代谢谱的长期影响。在12周内给大鼠分别给予三种剂量（14、28和56mg/kg）的补骨脂素和一种剂量（28mg/kg）的异补骨脂素。采集血液和选定的组织样本，进行血液学、血清生化和组织病理学分析。通过质子核磁共振（H-NMR）光谱检测血清样本中的代谢变化。我们发现补骨脂素显著改变了内脏系数、血液生化参数和组织病理学，而异补骨脂素额外影响了血液学指标。此外，补骨脂素使缬氨酸、异亮氨酸、异丁酸、丙氨酸、丙酮、丙酮酸、谷氨酰胺、柠檬酸、不饱和脂质、胆碱、肌酸、苯丙氨酸和4-羟基苯甲酸显著升高，乙醇和二甲基砜显著降低。异补骨脂素仅引起少数代谢物的显著变化。这些结果表明，长期低剂量接触补骨脂素会导致丙氨酸代谢、谷氨酸代谢、尿素循环、葡萄糖-丙氨酸循环、氨循环、甘氨酸和丝氨酸代谢途径紊乱。补骨脂素和异补骨脂素对大鼠表现出不同的毒性特征。
