title: Metabolomics study on the toxicity of aconite root and its processed products using ultraperformance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry coupled with pattern recognition approach and ingenuity pathways analysis.
abstract: The mother and lateral root of Aconitum carmichaelii Debx, named "Chuanwu" (CW) and "Fuzi", respectively, has been used to relieve joint pain and treat rheumatic diseases for over 2000 years. However, it has a very narrow therapeutic range, and the toxicological risk of its usage remains very high. The traditional Chinese processing approach, Paozhi (detoxifying measure),can decompose poisonous Aconitum alkaloids into less or nontoxic derivatives and plays an important role in detoxification. The difference in metabolomic characters among the crude and processed preparations is still unclear, limited by the lack of sensitive and reliable biomarkers. Therefore, this paper was designed to investigate comprehensive metabolomic characters of the crude and its processed products by UPLC-Q-TOF-HDMS combined with pattern recognition methods and ingenuity pathway analysis (IPA). The significant difference in metabolic profiles and changes of metabolite biomarkers of interest between the crude and processed preparations were well observed. The underlying regulations of Paozhi-perturbed metabolic pathways are discussed according to the identified metabolites, and four metabolic pathways are identified using IPA. The present study demonstrates that metabolomic analysis could greatly facilitate and provide useful information to further comprehensively understand the pharmacological activity and potential toxicity of processed Aconite roots in the clinic.
authors: National TCM Key Lab of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine , and Key Pharmacometabolomics Platform of Chinese Medicines, Heping Road 24, Harbin 150040, China. xijunwangls@126.com
authors: Xijun
authors: X
authors: Wang
authors: Huiyu
authors: H
authors: Wang
authors: Aihua
authors: A
authors: Zhang
authors: Xin
authors: X
authors: Lu
authors: Hui
authors: H
authors: Sun
authors: Hui
authors: H
authors: Dong
authors: Ping
authors: P
authors: Wang
mesh_terms: D031841:Aconitum / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004365:Drugs, Chinese Herbal / Q000633:toxicity*; D006651:Histocytochemistry; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D015999:Multivariate Analysis; D009206:Myocardium / Q000737:chemistry / Q000648:ultrastructure; D010363:Pattern Recognition, Automated / Q000379:methods; D018517:Plant Roots / Q000633:toxicity; D025341:Principal Component Analysis; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D015415:Biomarkers; D004365:Drugs, Chinese Herbal