title: Subchronic toxicity studies with ginsenoside compound K delivered to dogs via intravenous administration.
abstract: Compound K, i.e., 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol, is the main metabolite of the protopanaxadiol type of ginseng saponin produced by intestinal bacteria after oral administration of ginseng extract. In the present study, the toxicity of compound K was evaluated in male and female dogs after 90 days continuous intravenous infusion. Beagle dogs were treated with compound K at doses of 6.7, 20 and 60 mg/kg/day, and observed for 90 days followed by recovery periods. Measurements included clinical observations, body weight, food consumption, temperature, electrocardiogram (ECG), hematology, blood chemistry, urinalysis, gross necropsy, organ weight and histopathology. Under the conditions, the clinical condition of the animals, body weights, body weight gains and food consumption were unaffected by compound K administration relative to the control group. Hematology, ECG data and urinalysis parameters were also unaffected. However, the hepatotoxicity was evident from the observation of multiple parameters, including histopathological evaluation of liver tissue upon necropsy as well as large increases in plasma levels of liver enzymes (alanine aminotransferase, ALT, Gamma-glutamyltranspeptidase, γ-GT, alkaline phosphatase,ALP) in groups receiving compound K (20 or 60 mg/kg/day), and this hepatoxicity might be reversible. In addition, the NOAEL of compound K is 6.7 mg/kg/day in this 90 days toxicity study.
authors.affiliation: Science and Engineering College of Chemistry and Biology, Yantai University, Yantai 264005, PR China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Gao
authors.forename: Z F
authors.initials: ZF
authors.lastname: Liu
authors.forename: C M
authors.initials: CM
authors.lastname: Li
authors.forename: J Y
authors.initials: JY
authors.lastname: Shen
authors.forename: H X
authors.initials: HX
authors.lastname: Yin
authors.forename: G S
authors.initials: GS
authors.lastname: Li
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D036145:Ginsenosides / Q000737:chemistry / Q000633:toxicity*; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D005894:Panax / Q000737:chemistry; D010936:Plant Extracts / Q000633:toxicity*; D036401:Toxicity Tests, Chronic / Q000379:methods*; D016482:Urinalysis
chemical_list: D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D036145:Ginsenosides; D010936:Plant Extracts; C112772:ginsenoside compound K