title: The assessment of the chronic hepatotoxicity induced by Polygoni Multiflori Radix in rats: A pilot study by using untargeted metabolomics method.
abstract: Polygoni Multiflori Radix is the dried root of Polygonum multiflorum Thunb officially recorded in the Chinese Pharmacopoeia as HeShouWu (HSW) in Chinese pinyin. The processed HSW are commonly used in TCM to treat liver disease and Chinese Pharmacopoeia has described the actions of it to tonify liver-kidney, replenish essence and blood, blacken beard and hair, strengthen sinew and bone, and resolve turbidity and lower lipid hence making it use not only as a herbal medicine in TCM but also as supplementary food in health care.
  
  
  OBJECTIVE
  Concerns about the hepatotoxicity in association with Polygoni Multiflori Radix and its processed products have been reported in some countries. In the present study, we aim to investigate the potential hepatotoxicity of HSW in rats with oral administration of 95% ethanol-extracts of Polygoni Multiflori Radix by using metabolomics method.
  
  
  METHODS
  Here, male rats with 150-180g body weight were received vehicle control or Polygoni Multiflori Radix extracts (HSW-Ex) orally at 19.2 (low dose), 192 (medium dose), or 1920mg/kg/day (high dose), respectively, for 28 consecutive days. Signs of HSW-induced toxicity were monitored by traditional toxicity assessments (e.g., clinical pathology and histopathology). Metabolomics investigation of serum was performed to identify potential endogenous metabolites which may be relevant to liver injury.
  
  
  RESULTS
  Rats received High and Medium dose of HSW-Ex showed greater sign of liver injury with increased levels of ASP, ALT, and AST, as well as reduced SOD activity when compared to vehicle control. In contrast, there are no significant changes relevant to liver injury observed in rats by receiving the low dose of HSW-Ex. Metabolomics analyses have identified ten potential endogenous metabolites varied significantly among the treatment groups with varying doses of HSW-Ex, of which might be related to liver injury.
  
  
  CONCLUSIONS
  Our data has further suggested that liver damage resulting from HSW-Ex consumption is dosage dependent in rats. It is possible that disruption in amino acid and energy metabolism might lead to subsequent oxidative damage in the liver of rats. Because the clinic practice often use low dose in a short time, therefore HSW usage in TCM still keep safe currently, but we present a warning to the clinical doctors and make them has some concern about high dose of HSW usage in a long term that has potential danger to damage liver.
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, No.151 West Yanjiang Road, Yuexiu District, Guangzhou, Guangdong Province 510120, PR China. Electronic address: star1124@163.com.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Xia
authors.affiliation: Guangzhou Medical University, No. 195 West Dongfeng Road, Yuexiu District, Guangzhou, Guangdong Province 510182, PR China. Electronic address: 173179866@qq.com.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Yuan
authors.affiliation: School of Chinese Material Medical of Guangzhou University of Chinese Medicine, 232 East Waihuan Rd, High Education Mega Center, Panyu District, Guangzhou, Guangdong Province 510006, PR China. Electronic address: liumei2007@gzucm.edu.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000187:drug effects; D008297:Male; D055432:Metabolomics / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity*; D018517:Plant Roots; D028502:Polygonum / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000596:Amino Acids; D010936:Plant Extracts
keywords: Hepatotoxicity; Liver injury; Metabolomics; Polygoni Multiflori Radix; Polygonum multiflorum