期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 17, 期 -, 页码 1831-1846出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S406551
关键词
Arisaematis rhizome; nephrotoxicity; processing; UPLC-Q; TOF-MS; metabolomics
This study investigated the metabolic shifts induced by Arisaematis Rhizome (AR) and explored the processing mechanism using metabolomics and network analysis. The results showed that crude AR caused kidney damage, while processing alleviated this damage. Metabolomics analysis identified several metabolic pathways associated with AR nephrotoxicity and the toxic-reducing effect of processing.
Background: Arisaematis Rhizome (AR) has been used as a damp-drying, phlegm-resolving, wind-expelling, pain-alleviating, and swelling-relieving drug for thousands of years. However, the toxicity limits its clinical applications. Therefore, AR is usually processed (Paozhi in Chinese) prior to clinical use. In this study, the integration of ultra-high performance liquid chromatographyquadrupole/ time-of-flight mass spectrometry-based metabolomics and network analysis was adopted to investigate the metabolic shifts induced by AR and explore the processing mechanism. Materials and Methods: Extracts of crude and processed AR products (1g/kg) were intragastrically administered to rats once daily for four consecutive weeks. The renal function was evaluated by blood urea nitrogen, creatinine, interleukin-1 beta (IL-1 & beta;) and tumor necrosis factor-alpha (TNF-& alpha;), malondialdehyde (MDA), super oxide dismutase (SOD), the ratio of glutathione/glutathione disulfide (GSH/GSSH), glutathione peroxidase (GSH-Px) and histopathological examination. Furthermore, the chemical composition of AR was clarified by ultrahigh performance liquid chromatography-quadrupole/ time-of-flight mass spectrometry, after which the integration of metabolomics and network analysis was adopted to investigate the metabolic shifts induced by AR and explore the processing mechanism. Results: Crude AR caused renal damage by stimulating inflammation and oxidative stress, as confirmed by the increased production of IL-1 & beta;, TNF-& alpha; and MDA, and decreased levels of SOD, GSH/GSSH and GSH-Px. Processing with ginger juice, alumen and bile juice alleviated the damage to kidney. Metabolomics results showed that a total of 35 potential biomarkers enriched in amino acid metabolism, glycerophospholipid metabolism, fatty acid-related pathways, etc. were deduced to be responsible for the nephrotoxicity of AR and the toxicity-reducing effect of processing. Conclusion: This work provided theoretical and data support for the in-depth study of the processing mechanism, showing that processing reduces AR nephrotoxicity through multiple metabolic pathways.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据