title: Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts ofPolygonum multiflorumin Rats Integrated with Pattern Recognition and Enriched Pathways Analysis.
abstract: Currently, numerous liver injury cases related to a famous Chinese herb-Polygonum Multiflorum(Heshouwu in Chinese) have attracted great attention in many countries. Our previous work showed that Heshouwu-induced hepatotoxicity belonged to idiosyncratic drug-induced liver injury (IDILI). Unfortunately, the components and mechanisms attributed to IDILI of Heshouwu are difficult to determine and thus remain unknown. Attempts to explore puzzles, we prepared the chloroform (CH)-, ethyl acetate (EA)-, and residue (RE) extracts of Heshouwu to investigate IDILI constituents and underlying mechanisms, using biochemistry, histopathology, and metabolomics examinations. The results showed that co-treatment with non-toxic dose of lipopolysaccharide (LPS) and EA extract could result in evident liver injury, indicated by the significant elevation of plasma alanine aminotransferase and aspartate aminotransferase activities, as well as obvious liver histologic damage; whereas other two separated fractions, CH and RE extracts, failed to induce observable liver injury. Furthermore, 21 potential metabolomic biomarkers that differentially expressed in LPS/EA group compared with other groups without liver injury were identified by untargeted metabolomics, mainly involved two pathways: tricarboxylic acid cycle and sphingolipid metabolism. This work illustrated EA extract had close association with the idiosyncratic hepatotoxicity of Heshouwu and provided a metabolomic insight into IDILI of different extracts from Heshouwu.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, China; China Military Institute of Chinese Medicine, 302 Military HospitalBeijing, China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military HospitalBeijing, China; School of Pharmacy, Chengdu University of Traditional Chinese MedicineChengdu, China.
authors.forename: Can
authors.initials: C
authors.lastname: Tu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, China; China Military Institute of Chinese Medicine, 302 Military HospitalBeijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.affiliation: Integrative Medical Center, 302 Military Hospital Beijing, China.
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Wang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military HospitalBeijing, China; School of Pharmacy, Chengdu University of Traditional Chinese MedicineChengdu, China.
authors.forename: Hai-Zhu
authors.initials: HZ
authors.lastname: Zhang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Niu
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital Beijing, China.
authors.forename: Rui-Yu
authors.initials: RY
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital Beijing, China.
authors.forename: Cong-En
authors.initials: CE
authors.lastname: Zhang
authors.affiliation: Research Center for Clinical and Translational Medicine, 302 Hospital of People's Liberation Army Beijing, China.
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Li
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital Beijing, China.
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Xiao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Yang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Military Hospital Beijing, China.
authors.forename: Jia-Bo
authors.initials: JB
authors.lastname: Wang
keywords: Polygonum multiflorum; idiosyncratic liver injury; metabolomics; pathway analysis; stilbenes