Shoubei Qiu1, Haixia Zhang2, Qianqian Fei1, Fenxia Zhu3, Jing Wang3, Xiaobin Jia3, Bin Chen4. 1. 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. 2. Department of Pharmacy, Nanjing university medical school Affiliated Nanjing Drum Tower Hospital, Nanjing 210008, China. 3. 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. 4. 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. Electronic address: jeromechen@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Gynura segetum (GS) is an herbal medicine containing Pyrrolizidine Alkaloids (PAs) that causes hepatic sinusoidal obstruction syndrome (HSOS). AIM OF THE STUDY: To discover potential biomarkers and metabolic mechanisms involved in the hepatotoxicity induced by GS. METHODS: 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-1, 7.5g • kg-1 and 15g • kg-1. 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. RESULTS: 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. CONCLUSIONS: 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.
ETHNOPHARMACOLOGICAL RELEVANCE: Gynura segetum (GS) is an herbal medicine containing Pyrrolizidine Alkaloids (PAs) that causes hepatic sinusoidal obstruction syndrome (HSOS). AIM OF THE STUDY: To discover potential biomarkers and metabolic mechanisms involved in the hepatotoxicity induced by GS. METHODS: 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-1, 7.5g • kg-1 and 15g • kg-1. 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Ruth R Magaye; Feby Savira; Yue Hua; Darren J Kelly; Christopher Reid; Bernard Flynn; Danny Liew; Bing H Wang Journal: Cell Mol Life Sci Date: 2018-12-06 Impact factor: 9.261