title: 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.
abstract: Chuanwu (CW), a famous traditional Chinese medicine (TCM) from the mother roots of Aconitum carmichaelii Debx.. (Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequently reported because of its narrow therapeutic window. In the present study, a metabolomic method was performed to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity. Meanwhile, the expression level of toxicity biomarkers in the urine were analyzed to evaluate the detoxification by combination with Gancao (Radix Glyeyrrhizae, CG), Baishao (Radix Paeoniae Alba, CS) and Ganjiang (Rhizoma Zingiberis, CJ), which were screened from classical TCM prescriptions. Urinary metabolomics was performed by UPLC-Q-TOF-HDMS, and the mass spectra signals of the detected metabolites were systematically analyzed using pattern recognition methods. As a result, seventeen biomarkers associated with CW toxicity were identified, which were associated with pentose and glucuronate interconversions, alanine, aspartate, and glutamate metabolism, among others. The expression levels of most toxicity biomarkers were effectively modulated towards the normal range by the compatibility drugs. It indicated that the three compatibility drugs could effectively detoxify CW. In summary, our work demonstrated that metabolomics was vitally significant to evaluation of toxicity and finding detoxification methods for TCM.
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Guang-Li
authors.initials: GL
authors.lastname: Yan
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China. Electronic address: pca1970@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Zhang
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Xian-Na
authors.initials: XN
authors.lastname: Li
authors.affiliation: National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics and Chinmedomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin 150040, China. Electronic address: xijun-wangls@126.com.
authors.forename: Xi-Jun
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D031841:Aconitum / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism* / Q000517:prevention & control; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D020939:Zingiber officinale; D029882:Glycyrrhiza uralensis; D006321:Heart; D008658:Inactivation, Metabolic; D008099:Liver; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008516:Medicine, Chinese Traditional; D055442:Metabolome; D055432:Metabolomics; D029596:Paeonia; D018517:Plant Roots; D017208:Rats, Wistar; D027343:Rhizome
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal
keywords: Aconitum; Chuanwu; Compatibility; Detoxification; Metabolomics