title: Pre-clinical in vitro and in vivo safety evaluation of Cimicifuga heracleifolia.
abstract: The rhizomes of Cimicifuga species, including Cimicifuga heracleifolia (CH), have been widely used as antipyretic, analgesic, and anti-inflammatory agents in oriental countries. However, information regarding its toxicity, especially long-term toxicity and genotoxicity, is limited. Therefore, we performed the subchronic toxicity and genotoxicity assays of the CH extract in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In a 13-week repeat-dose oral toxicity study, the CH extract did not influence body weight, food/water consumption, mortality, clinical signs, and urinalysis throughout the study. Noteworthy, the CH extract groups exhibited increased liver weights along with serum alanine transaminase activity rise at doses of 667 and 2000 mg/kg in females. No-observed-adverse-effect-level of the CH extract administered orally was concluded to be 2000 mg/kg body weight/day for male rats and 222 mg/kg body weight/day for female rats. The CH extract did not exert a mutagenic or clastogenic effect in Ames test, in vitro chromosome aberration assay and in vivo micronucleus assay. Overall findings of the subchronic toxicity study indicate for the first time that the CH extract may possess hepatotoxic potential in female rats, suggesting that further mechanistic studies should be performed to have more conclusive results on hepatotoxic potential of the CH extract.
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Jun-Won
authors.initials: JW
authors.lastname: Yun
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Ji-Ran
authors.initials: JR
authors.lastname: You
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Yun-Soon
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Euna
authors.initials: E
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ja-June
authors.initials: JJ
authors.lastname: Jang
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Biomedical Center for Animal Resource and Development, N-BIO, Seoul National University, Seoul, Republic of Korea. Electronic address: casache@snu.ac.kr.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Che
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Biomedical Center for Animal Resource and Development, N-BIO, Seoul National University, Seoul, Republic of Korea; Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Designed Animal and Transplantation Research Institute, Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, Republic of Korea. Electronic address: bckang@snu.ac.kr.
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Kang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced; D031885:Cimicifuga / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D059550:Toxicity Tests, Subchronic / Q000379:methods
chemical_list: D010936:Plant Extracts
keywords: Cimicifuga heracleifolia; Genotoxicity; Hepatotoxicity; Subchronic toxicity; Traditional medicine