Cao Sa, Han Lintao, Li Yamin, Yao Shiqi, Hou Shuaihong, Ma Shi-Shi, Dai Wangqiang, Li Jingjing, Zhou Zhenxiang, Wang Qiong, Huang Fang
Department of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China.
Department of Chinese Medicine Resource and Compound Prescription, Ministry of Education, Wuhan, Hubei 430065, P.R. China.
Exp Ther Med. 2020 Aug;20(2):1359-1370. doi: 10.3892/etm.2020.8811. Epub 2020 May 28.
Asarum is frequently applied in combination with other agents for prescriptions in practices of Traditional Chinese Medicine. A number of studies have previously indicated that asarum treatment induces lung toxicity by triggering inflammation. However, the potential effects of asarum in the liver and the underlying mechanisms have remained largely elusive. Therefore, transcriptomics and metabolomics approaches were used in the present study to examine the mechanisms of the hepatotoxicity of asarum. Specifically, mRNA and metabolites were obtained from rat liver samples following intragastric administration of asarum powder. RNA sequencing analysis was subsequently performed to screen for differentially expressed genes (DEGs), and a total of 434 DEGs were identified in liver tissue samples, 214 of which were upregulated and 220 were downregulated. Pathway enrichment analysis found that these genes were particularly enriched in processes including the regulation of p53 signaling, metabolic pathways and bile secretion. To investigate potential changes to the metabolic profile as a result of asarum treatment, a metabolomics analysis was performed, which detected 14 significantly altered metabolites in rat liver samples by gas chromatography-mass spectrometry. These metabolites were predominantly members of the taurine, hypotaurine and amino acid metabolic pathways. Metscape network analyses were subsequently performed to integrate the transcriptomics and metabolomics data. Integrative analyis revealed that the DEGs and metabolites were primarily associated with bile acid biosynthesis, amino acid metabolism and the p53 signaling pathway. Taken together, these results provide novel insight into the mechanism of asarum-mediated hepatotoxicity, which may potentially aid the clinical diagnosis and future therapeutic intervention of asarum poisoning.
细辛在中医临床实践中常与其他药物配伍使用。此前多项研究表明，细辛治疗可通过引发炎症导致肺毒性。然而，细辛对肝脏的潜在影响及其潜在机制在很大程度上仍不清楚。因此，本研究采用转录组学和代谢组学方法来研究细辛肝毒性的机制。具体而言，在大鼠灌胃细辛粉末后，从其肝脏样本中获取mRNA和代谢产物。随后进行RNA测序分析以筛选差异表达基因（DEG），在肝脏组织样本中总共鉴定出434个DEG，其中214个上调，220个下调。通路富集分析发现，这些基因特别富集于包括p53信号通路调节、代谢途径和胆汁分泌等过程。为了研究细辛处理后代谢谱的潜在变化，进行了代谢组学分析，通过气相色谱-质谱法在大鼠肝脏样本中检测到14种显著改变的代谢产物。这些代谢产物主要是牛磺酸、亚牛磺酸和氨基酸代谢途径的成员。随后进行Metscape网络分析以整合转录组学和代谢组学数据。综合分析表明，DEG和代谢产物主要与胆汁酸生物合成、氨基酸代谢和p53信号通路相关。综上所述，这些结果为细辛介导的肝毒性机制提供了新的见解，这可能有助于细辛中毒的临床诊断和未来的治疗干预。
