UPLC-Q-TOF/MS-based metabolomic studies on the toxicity mechanisms of traditional Chinese medicine Chuanwu and the detoxification mechanisms of Gancao, Baishao, and Ganjiang

Dong, Honglin; Ge, Yan; Han, Ying; Sun, Hui; Zhang, Aihua; Li, Xianna; Wang, Xijun

doi:10.1016/s1875-5364(15)30067-4

Cited by 16 publications

(14 citation statements)

References 29 publications

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“…Glucuronidation played a role in phase II metabolism, which could conjugate with toxic substance such as brucine, and facilitate its elimination. Besides, liquorice may generate chemical precipitations with alkaloids . Meanwhile, brucine had a great role in the AUC 0‐∞ of glycyrrhizic acid, the AUC 0‐t , AUC 0‐∞ , t 1/2 of liquiritigenin, and the AUC 0‐t , AUC 0‐∞ of liquiritin, suggesting significant drug interaction between brucine and liquorice.…”

Section: Resultsmentioning

confidence: 99%

“…Besides, liquorice may generate chemical precipitations with alkaloids. 12 Meanwhile, brucine had a great role in the AUC 0-∞ of glycyrrhizic acid, the AUC 0-t , AUC 0-∞ , t 1/2 of liquiritigenin, and the AUC 0-t , AUC 0-∞ of liquiritin, suggesting significant drug interaction between brucine and liquorice. And glycyrrhizic acid, liquiritigenin, and liquiritin were the most possible effective constituents in liquorice.…”

Section: Stabilitymentioning

confidence: 98%

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An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

Zhang

Deng

Wang

et al. 2017

Drug Testing and Analysis

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Semen Strychni is known for its treatment of rheumatic arthritis with a low therapeutic index. Liquorice contributes a lot in herb detoxification according to the traditional Chinese medicine theory. A simple, rapid, and sensitive liquid chromatography-mass spectrometric method (LC-MS) was developed and validated for simultaneous determination of main bioactive ingredients in liquorice and Semen Strychni in rat plasma. Using moclobemide and cyproterone acetate as the internal standards, the analytes were pretreated via protein precipitation with methanol. An Ultimate AQ-C18 column (3.0 μm, 3.0 × 100 mm) was employed for chromatographic separation, combining with gradient elution. The mobile phase consisted of 0.07% formic acid and 0.12% ammonium acetate in aqueous phase (A) and acetonitrile in organic phase (B). The elution program was as follows: 0-0.5 min, 20% B; 0.5-1 min, 20-60% B; 1-7 min, 60-85% B; and 7-7.5 min, returned to 20% B, then continued to 12 min. Selected reaction monitoring was performed in both positive and negative ESI. Positive mode was adopted for detection of strychnine, brucine, and moclobemide, while negative mode was used for glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, liquiritin, and cyproterone acetate. The method was validated for specificity, linearity, matrix effect, recovery, precision, accuracy, and stability. The results show that this method is sensitive, accurate and robust for biological matrix analysis. Moreover, the proposed method was applied to a pharmacokinetic study in Sprague-Dawley rats for investigating the mechanism of which liquorice detoxifies Semen Strychni.

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Section: Resultsmentioning

confidence: 99%

Section: Stabilitymentioning

confidence: 98%

An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

Zhang

Deng

Wang

et al. 2017

Drug Testing and Analysis

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“…In recent years, metabolomics has been widely applied in the identification of biomarkers related to drug toxicity and revealing the mechanisms of toxicity via changes in endogenous metabolites (Gonzalez, Fang, & Ma, ). Since this systematic analysis strategy is highly consistent with the theory of traditional Chinese medicine, increasing numbers of studies have applied metabolomics to investigate traditional Chinese medicine efficacy and toxicity (Cao, Zhang, Zhang, Sun, & Wang, ; Dong et al, ). Some studies have used metabolomic technologies to investigate the possible mechanisms of triptolide‐induced hepatotoxicity.…”

Section: Introductionmentioning

confidence: 89%

“…increasing numbers of studies have applied metabolomics to investigate traditional Chinese medicine efficacy and toxicity (Cao, Zhang, Zhang, Sun, & Wang, 2015;Dong et al, 2015). Some studies have used metabolomic technologies to investigate the possible mechanisms of triptolide-induced hepatotoxicity.…”

mentioning

confidence: 99%

Metabolic alterations in triptolide‐induced acute hepatotoxicity

Zhao

Xie

et al. 2018

Biomedical Chromatography

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Triptolide, a major active constitute of Tripterygium wilfordii Hook. F, is prescribed for the treatment of autoimmune diseases in China. One of its most severe adverse effects observed in the clinical use is hepatotoxicity, but the mechanism is still unknown. Therefore, the present study applied an LC/MS-based metabolomic analysis to characterize the metabolomic changes in serum and liver induced by triptolide in mice. Mice were administered triptolide by gavage to establish the acute liver injury model, and serum biochemical and liver histological analyses were applied to assess the degree of toxicity. Multivariate data analyses were performed to investigate the metabolic alterations. Potential metabolites were identified using variable importance in the projection values and Student's t-test. A total of 30 metabolites were observed that were significantly changed by triptolide treatment and the abundance of 29 metabolites was correlated with the severity of toxicity. Pathway analysis indicated that the mechanism of triptolide-induced hepatotoxicity was related to alterations in multiple metabolic pathways, including glutathione metabolism, tricarboxylic acid cycle, purine metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism and amino acid metabolism. The current study provides new mechanistic insights into the metabolic alterations that lead to triptolide-induced hepatotoxicity.

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“…With advanced and comprehensive data collection technology, integrity and system phenotypic characterization could be precisely obtained. [3][4][5][6][7][8][9][10] Moreover, a robust analysis platform provides unparalleled technical support. With high throughput and resolution, SYNAPT™-G2Si-HDMS possesses the latest technology in ion mobility spectrometry performance, which combined with the proprietary technology of T-wave™ and Quantof can greatly improve the resolution and sensitivity into 40 000 and 10 000 dpi, respectively.…”

Section: Introductionmentioning

confidence: 99%

Discovery and verification of the potential targets from bioactive molecules by network pharmacology-based target prediction combined with high-throughput metabolomics

et al. 2017

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UPLC-Q-TOF/MS-based metabolomic studies on the toxicity mechanisms of traditional Chinese medicine Chuanwu and the detoxification mechanisms of Gancao, Baishao, and Ganjiang

Cited by 16 publications

References 29 publications

An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study

Metabolic alterations in triptolide‐induced acute hepatotoxicity

Discovery and verification of the potential targets from bioactive molecules by network pharmacology-based target prediction combined with high-throughput metabolomics

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