Wu Fang, Zheng Hua, Yang Zheng-Teng, Cheng Bang, Wu Jin-Xia, Liu Xu-Wen, Tang Chao-Ling, Lu Shi-Yin, Chen Zhao-Ni, Song Fang-Ming, Ruan Jun-Xiang, Zhang Hong-Ye, Liang Yong-Hong, Song Hui, Su Zhi-Heng
Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
Medical Scientific Research Center, Guangxi Medical University, Nanning 530021, China.
J Pharm Biomed Anal. 2017 Jun 5;140:199-209. doi: 10.1016/j.jpba.2017.03.031. Epub 2017 Mar 19.
Chronic liver injury has been shown to cause liver fibrosis due to the sustained pathophysiological wound healing response of the liver, and eventually progresses to cirrhosis. The total alkaloids of Corydalis saxicola Bunting (TACS), a collection of important bioactive ingredients derived from the traditional Chinese folk medicine Corydalis saxicola Bunting (CS), have been reported to have protective effects on the liver. However, the underlying molecular mechanisms need further elucidation. In this study, the urinary metabonomics and the biochemical changes in rats with carbon tetrachloride (CCl)-induced chronic liver injury due to treatment TACS or administration of the positive control drug-bifendate were studied via proton nuclear magnetic resonance (H NMR) analysis. Partial least squares-discriminate analysis (PLS-DA) suggested that metabolic perturbation caused by CCl damage was recovered with TACS and bifendate treatment. A total of seven metabolites including 2-oxoglutarate, citrate, dimethylamine, taurine, phenylacetylglycine, creatinine and hippurate were considered as potential biomarkers involved in the development of CCl-induced chronic liver injury. According to pathway analysis using identified metabolites and correlation network construction, the tricarboxylic acid (TCA) cycle, gut microbiota metabolism and taurine and hypotaurine metabolism were recognized as the most affected metabolic pathways associated with CCl chronic hepatotoxicity. Notably, the changes in 2-oxoglutarate, citrate, taurine and hippurate during the process of CCl-induced chronic liver injury were significantly restored by TACS treatment, which suggested that TACS synergistically mediated the regulation of multiple metabolic pathways including the TCA cycle, gut microbiota metabolism and taurine and hypotaurine metabolism. This study could bring valuable insight to evaluating the efficacy of TACS intervention therapy, help deepen the understanding of the hepatoprotective mechanisms of TACS and enable optimal diagnosis of chronic liver injury.
慢性肝损伤已被证明会由于肝脏持续的病理生理创伤愈合反应而导致肝纤维化，并最终发展为肝硬化。岩黄连总生物碱（TACS）是从传统中药岩黄连（CS）中提取的一组重要生物活性成分，据报道对肝脏具有保护作用。然而，其潜在的分子机制尚需进一步阐明。在本研究中，通过质子核磁共振（H NMR）分析，研究了用TACS治疗或给予阳性对照药物联苯双酯的情况下，四氯化碳（CCl）诱导的慢性肝损伤大鼠的尿液代谢组学及生化变化。偏最小二乘判别分析（PLS-DA）表明，TACS和联苯双酯治疗可恢复由CCl损伤引起的代谢紊乱。共有七种代谢物，包括2-氧代戊二酸、柠檬酸、二甲胺、牛磺酸、苯乙酰甘氨酸、肌酐和马尿酸，被认为是参与CCl诱导的慢性肝损伤发展的潜在生物标志物。根据使用已鉴定代谢物的通路分析和相关网络构建，三羧酸（TCA）循环、肠道微生物群代谢以及牛磺酸和亚牛磺酸代谢被认为是与CCl慢性肝毒性相关的受影响最大的代谢通路。值得注意的是，TACS治疗可显著恢复CCl诱导的慢性肝损伤过程中2-氧代戊二酸、柠檬酸、牛磺酸和马尿酸的变化，这表明TACS协同介导了包括TCA循环、肠道微生物群代谢以及牛磺酸和亚牛磺酸代谢在内的多种代谢通路的调节。本研究可为评估TACS干预疗法的疗效提供有价值的见解，有助于加深对TACS肝保护机制的理解，并实现对慢性肝损伤的最佳诊断。
