Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Shi Zi Street No. 100, Hongshan Road, Jiangsu, Nanjing 210028, China; Key Laboratory of Chinese Medicine Delivery System of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Shi Zi Street No. 100, Hongshan Road, Jiangsu, Nanjing 210028, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Pharmacy, Nanjing university medical school Affiliated Nanjing Drum Tower Hospital, Nanjing 210008, China.
J Ethnopharmacol. 2018 Apr 24;216:37-46. doi: 10.1016/j.jep.2018.01.017. Epub 2018 Jan 17.
Gynura segetum (GS) is an herbal medicine containing Pyrrolizidine Alkaloids (PAs) that causes hepatic sinusoidal obstruction syndrome (HSOS).
To discover potential biomarkers and metabolic mechanisms involved in the hepatotoxicity induced by GS.
SD rats were randomly divided into 4 groups including Saline, the decoction of GS high, medium and low dosage at dosages of 3.75g • kg, 7.5g • kg and 15g • kg. A metabolomics approach using Ultraperformance Liquid Chromatography -Quadrupole-Time-of-Flight / Mass Spectrometry (UPLC-Q-TOF/MS) was developed to perform the plasma and urinary metabolic profiling analysis, and identified differential metabolites by comparing the saline control group and decoction of GS groups.
The herbal was presented dosage-dependent led to ingravescence of hepatotoxicity after the rats were consecutively given with the decoction of GS at varied dosages. A total of 18 differential metabolites of decoction of GS-induced hepatotoxicity were identified, while 10 of them including arginine, proline, glutamate, creatine, valine, linoleic acid, arachidonic acid, sphinganine, phytosphingosine, and citric acid could be discovered in urine and plasma, and primarily involved in Amino acid metabolism, Lipids metabolism and Energy metabolism.
The results suggested that the differential metabolites of arginine, creatine, valine, glutamine and citric acid were verified as potential markers of GS-induced hepatotoxicity via the regulation of multiple metabolic pathways primarily involving in Amino acids metabolism and Energy metabolism.
三叶鬼针草（GS）是一种含有吡咯里西啶生物碱（PAs）的草药，可引起肝窦阻塞综合征（HSOS）。
发现与 GS 诱导的肝毒性相关的潜在生物标志物和代谢机制。
SD 大鼠随机分为 4 组，包括生理盐水组、GS 高、中、低剂量组（剂量分别为 3.75g•kg、7.5g•kg 和 15g•kg）。采用超高效液相色谱-四极杆飞行时间/质谱联用（UPLC-Q-TOF/MS）建立代谢组学方法，对血浆和尿液进行代谢谱分析，并通过比较生理盐水对照组和 GS 汤组来鉴定差异代谢物。
该草药呈现剂量依赖性，大鼠连续给予不同剂量 GS 汤后，肝毒性逐渐加重。共鉴定出 18 种 GS 汤诱导肝毒性的差异代谢物，其中 10 种代谢物包括精氨酸、脯氨酸、谷氨酸、肌酸、缬氨酸、亚油酸、花生四烯酸、鞘氨醇、神经鞘氨醇和柠檬酸，可在尿液和血浆中发现，主要涉及氨基酸代谢、脂质代谢和能量代谢。
结果表明，精氨酸、肌酸、缬氨酸、谷氨酰胺和柠檬酸的差异代谢物通过调节主要涉及氨基酸代谢和能量代谢的多条代谢途径，被验证为 GS 诱导肝毒性的潜在标志物。
