title: Deciphering the differential toxic responses of Radix aconiti lateralis praeparata in healthy and hydrocortisone-pretreated rats based on serum metabolic profiles.
abstract: Radix aconiti lateralis praeparata (Baifupian) has received great attention because of its excellent therapeutic effects as well as the associated adverse drug reactions. According to the traditional Chinese medicine (TCM) principle, Baifupian should only be used in patients with TCM "kidney-yang" deficiency pattern, a clinical state that can be mimicked by hydrocortisone induction in rats. This study aimed to decipher the differential toxic responses of Baifupian in healthy and hydrocortisone-pretreated rats based on serum metabolic profiles. Drug-treated rats received Baifupian intragastrically at the dose of 1.28 g/kg/day for 15 days. Serum metabolic profiles were obtained by using the LC-Q-TOF-MS technique. Our results show that Baifupian could induce severe toxicity in the heart, liver, and kidneys of healthy rats. These drug-induced toxic reactions were largely alleviated in hydrocortisone-pretreated animals. Changes of metabolic profiles in drug-treated healthy and hydrocortisone-pretreated rats were demonstrated, involving oxidative phosphorylation, amino acid and lipid metabolism as characterized by altered phosphate, betaine, and phosphatidyl choline. These metabolic alterations could be responsible at least in part for the differential toxic responses of Baifupian under various health conditions. This study provides a new paradigm for better understanding of the risks and limitations when using potentially toxic herbs in clinical applications.
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science, Beijing 100700, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tan
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Xinru
authors.initials: X
authors.lastname: Liu
authors.forename: Joshua
authors.initials: J
authors.lastname: Ko
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: He
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Liu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhao
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiao
authors.forename: Xuyan
authors.initials: X
authors.lastname: Niu
authors.forename: Qingling
authors.initials: Q
authors.lastname: Zha
authors.forename: Zhiling
authors.initials: Z
authors.lastname: Yu
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
mesh_terms: D031841:Aconitum / Q000737:chemistry; D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry; D008516:Medicine, Chinese Traditional; D055442:Metabolome / Q000235:genetics*; D051381:Rats; D016711:Yang Deficiency / Q000097:blood / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D006854:Hydrocortisone