Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, 300193, China; Ministry of Education Key Laboratory of Traditional Chinese Medical Formulae, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Regul Toxicol Pharmacol. 2019 Apr;103:1-9. doi: 10.1016/j.yrtph.2019.01.010. Epub 2019 Jan 8.
Isopsoralen is a major active and quality-control component of Fructus Psoraleae, but lacks a full safety evaluation. We evaluated the oral toxicity of isopsoralen in Wistar rats treated for 3 months at doses of 0, 3.5, 7.0, and 14 mg/kg. Additionally, the plasma metabolomics of isopsoralen in male and female rats treated for 3 months at doses of 0 and 14 mg/kg were investigated by gas chromatography-mass spectrometry. Many abnormalities were observed in the isopsoralen-treated rats, including suppression of body weight gain, and changes in serum biochemical parameters and visceral coefficients. Histopathological changes in liver, pancreatic, and reproductive system tissues were also observed in the isopsoralen-treated rats. The metabolomic analyses showed alterations in many metabolites (19 in female rats; 28 in male rats) after isopsoralen administration. The significant changes in these metabolites revealed metabolomic alterations in the isopsoralen-treated rats, especially in amino acid metabolism regardless of sex, including phenylalanine, tyrosine, and tryptophan biosynthesis and glycine, serine, and threonine metabolism. Furthermore, fatty acid metabolism comprised the main affected pathways in female rats, while lipid metabolism and energy metabolism were the main affected pathways in male rats.
补骨脂素是补骨脂的主要活性成分和质量控制成分，但缺乏全面的安全性评价。我们在雄性和雌性大鼠中评价了补骨脂素的口服毒性，大鼠在 3 个月内分别以 0、3.5、7.0 和 14mg/kg 的剂量进行处理。此外，还通过气相色谱-质谱法研究了雄性和雌性大鼠在 3 个月内以 0 和 14mg/kg 的剂量处理时补骨脂素的血浆代谢组学。在补骨脂素处理的大鼠中观察到许多异常，包括体重增加受到抑制，以及血清生化参数和内脏系数的变化。在补骨脂素处理的大鼠中还观察到肝、胰腺和生殖系统组织的组织病理学变化。代谢组学分析显示，补骨脂素给药后许多代谢物发生改变（雌性大鼠 19 种；雄性大鼠 28 种）。这些代谢物的显著变化揭示了补骨脂素处理大鼠的代谢组学改变，特别是在氨基酸代谢中，无论性别如何，包括苯丙氨酸、酪氨酸和色氨酸的生物合成以及甘氨酸、丝氨酸和苏氨酸代谢。此外，脂肪酸代谢是雌性大鼠中受影响的主要途径，而脂质代谢和能量代谢是雄性大鼠中受影响的主要途径。
