Ji Peng, Wei Yanming, Sun Hongguo, Xue Wenxin, Hua Yongli, Li Pengling, Zhang Wenquan, Zhang Ling, Zhao Haifu, Li Jinxia
Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China.
Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Dec 15;973C:45-54. doi: 10.1016/j.jchromb.2014.10.009. Epub 2014 Oct 18.
Angelica sinensis polysaccharides (ASP) have an established hepatoprotective effect, but the mechanism for this effect remains unclear. A novel approach using biochemical parameters coupled with metabolomics based on gas chromatography-mass spectrometry (GC-MS) and chemometrics was established in this study to explain the hepatoprotective effect mechanism of ASP. The superoxide dismutase activity, malonaldehyde content, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in plasma were measured. Pathological changes in the liver were observed. Plasma and liver homogenate obtained from mice were analyzed using GC-MS. Distinct changes in metabolite patterns in the plasma and liver homogenate after being induced by carbon tetrachloride and drug intervention were observed using principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Potential biomarkers were found using PLS-DA and T-test. The results of the pathological changes observed in the liver, the biochemical parameters in plasma, and the metabolomics of the plasma and liver homogenate all showed that liver injury was successfully reproduced, ASP exhibited hepatoprotective effect, and the medium dose of ASP exhibited the best. Nine endogenous metabolites in the liver homogenate and ten endogenous metabolites in the plasma were all considered as potential biomarkers. They were considered to be in response to hepatoprotective effects of ASP involved in the amino acids metabolism, energy metabolism, and lipids metabolism. Therefore metabolomics is a valuable tool in measuring the efficacy and mechanisms of action of traditional Chinese medicines.
当归多糖（ASP）具有明确的肝脏保护作用，但其作用机制尚不清楚。本研究建立了一种新方法，结合生化参数以及基于气相色谱-质谱联用（GC-MS）和化学计量学的代谢组学，以解释ASP的肝脏保护作用机制。检测了血浆中的超氧化物歧化酶活性、丙二醛含量、谷丙转氨酶、谷草转氨酶和γ-谷氨酰转肽酶。观察了肝脏的病理变化。对从小鼠获得的血浆和肝脏匀浆进行GC-MS分析。使用主成分分析（PCA）和偏最小二乘判别分析（PLS-DA）观察四氯化碳诱导和药物干预后血浆和肝脏匀浆中代谢物模式的明显变化。使用PLS-DA和T检验发现潜在生物标志物。肝脏病理变化结果、血浆生化参数以及血浆和肝脏匀浆的代谢组学均表明成功复制了肝损伤，ASP表现出肝脏保护作用，且中剂量的ASP表现最佳。肝脏匀浆中的9种内源性代谢物和血浆中的10种内源性代谢物均被视为潜在生物标志物。它们被认为与ASP参与氨基酸代谢、能量代谢和脂质代谢的肝脏保护作用有关。因此，代谢组学是衡量中药疗效和作用机制的有价值工具。
