Black cohosh (Cimicifuga racemosa L.) protects against menadione-induced DNA damage through scavenging of reactive oxygen species: bioassay-directed isolation and characterization of active principles.
The roots/rhizomes of Cimicifuga racemosa L. (Nutt.) (black cohosh) have traditionally been used to treat menopausal symptoms through an unknown mechanism of action. In an effort to determine if black cohosh had additional health benefits, methanol extracts were investigated for their potential to scavenge reactive oxygen species and to protect against menadione-induced DNA damage. These extracts effectively scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals. In addition, the extracts showed dose-dependent decreases in DNA single-strand breaks and oxidized bases induced by the quinone menadione using the comet (single-cell gel electrophoresis assay) and fragment length associated repair enzyme assays, respectively. Bioassay-directed fractionation of the methanolic extracts using the DPPH assay as a monitor led to the isolation of nine antioxidant active compounds: caffeic acid (1), methyl caffeate (2), ferulic acid (3), isoferulic acid (4), fukinolic acid (5), cimicifugic acid A (6), cimicifugic acid B (7), cimicifugic acid F (8), cimiracemate A (9), and cimiracemate B (10). Six of these antioxidants were found to reduce menadione-induced DNA damage in cultured S30 breast cancer cells with the following order of potency: methyl caffeate (2) > caffeic acid (1) > ferulic acid (3) > cimiracemate A (9) > cimiracemate B (10) > fukinolic acid (5). These data suggest that black cohosh can protect against cellular DNA damage caused by reactive oxygen species by acting as antioxidants.
Burdette
Joanna E
JE
Department of Medicinal Chemistry and Pharmacognosy and UIC/NIH Center for Botanical and Dietary Supplements Research, College of Pharmacy, 833 South Wood Street, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Chen
Shao-Nong
SN
Lu
Zhi-Zhen
ZZ
Xu
Haiyan
H
White
Bethany E P
BE
Fabricant
Daniel S
DS
Liu
Jianghua
J
Fong
Harry H S
HH
Farnsworth
Norman R
NR
Constantinou
Andreas I
AI
Van Breemen
Richard B
RB
Pezzuto
John M
JM
Bolton
Judy L
JL
D000975:Antioxidants / Q000302:isolation & purification* / Q000494:pharmacology; D001713:Biphenyl Compounds; D001943:Breast Neoplasms; D031885:Cimicifuga / Q000737:chemistry*; D004249:DNA Damage / Q000187:drug effects*; D047628:Estrogen Receptor alpha; D016166:Free Radical Scavengers / Q000302:isolation & purification* / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D000432:Methanol; D010851:Picrates / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D024483:Vitamin K 3 / Q000494:pharmacology*
D000975:Antioxidants; D001713:Biphenyl Compounds; D047628:Estrogen Receptor alpha; D016166:Free Radical Scavengers; D010851:Picrates; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D024483:Vitamin K 3; C004931:1,1-diphenyl-2-picrylhydrazyl; D000432:Methanol