1H NMR-based nontargeted metabonomics study of plasma and urinary biochemical changes in Kudouzi treated rats

Abstract Kudouzi (Sophora alopecuroides L., Fabaceae) is an effective folk medicine, but it always causes a hepatic and renal toxicity in clinical therapy. The toxic mechanism remains unclear. This paper detected the urinary and plasma metabolites alteration by 1H NMR-based metabonomics study in Kudouzi-induced rats to evaluate the toxic mechanism for clinical security. The male Sprague-Dawley rats were orally dosed with 0.5 and 1 g Kudouzi/kg weight once per day for consecutive 14 days. Urine samples were collected at day −1 (before treatment), and days 7, 14, and 21 for NMR analysis, respectively. Plasma samples were harvested at day 14 for NMR and biochemical analysis. The metabonomic profiling of Kudouzi-treated rats differed from that of the vehicle. This was confirmed by the biochemistry analysis. The accumulated subacute toxicity of Kudouzi was visible with dosing time, and persisted at day 21 even after the disposal was ended. The observable biochemical pathways alterations included inhibited TCA cycle, activated anaerobic glycolysis, perturbed amino acids metabolism, and disordered gut microbiota. The results evidenced the toxicity mechanism of Kudouzi from a systematic and holistic view.

Different processing methods change the oral toxicity induced by Sophora alopecuroides seeds and the contents of five main toxic alkaloids from the ethanol extracts determined by a validated UHPLC-MS/MS assay

Abstract This study investigated the influence of different processing methods on the oral toxicity of Sophora alopecuroides L., Fabaceae, seeds in mice and on the contents of five known toxic-effective quinolizidine alkaloids from the ethanol extracts quantified by ultra-performance liquid chromatography coupled to tandem quadrupole mass spectrometry. It provides an evidence to elucidate the possible reasons why vinegar-processing and parching methods significantly decrease the acute oral toxicity induced by S. alopecuroides and why wine-processing method increases it instead (demonstrated by measurement of LD50 and histopathological analysis). The analytical performance for the determination of the five analytes was evaluated by linearity, stability, repeatability, precision and accuracy, and recovery test. The lowest limit of quantification was determined to be 5 ng/ml for each substance and the precision and accuracy at lowest limit of quantification were below 20%. Cytisine, the most toxic alkaloid among the five alkaloids, declined 11.26, 3.98, and 2.73 folds after being vinegar-processed and fried in a ceramic or iron pan, respectively and had a very close correlation with the toxicity of S. alopecuroides seeds (r = 0.8589). Other matrine-type alkaloids with lower toxicity including matrine, sophcarpine, and sophoridine decreased after being wine-processed and fried in a ceramic pan, but increased 4.44, 7.20, and 7.23 folds when being processed by vinegar. Oxymatrine declined in all groups. It, therefore, reveals that vinegar-processing method reduces the oral toxicity of S. alopecuroides mainly due to a sharp decrease of cytisine, thus improves its clinical safety.