title: Toxins in botanical dietary supplements: blue cohosh components disrupt cellular respiration and mitochondrial membrane potential.
abstract: Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA "black box" warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3), exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage.
authors: Department of Pharmacognosy, ‡National Center for Natural Products Research, and ⊥Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi , University, Mississippi 38677, United States.
authors: Sandipan
authors: S
authors: Datta
authors: Fakhri
authors: F
authors: Mahdi
authors: Zulfiqar
authors: Z
authors: Ali
authors: Mika B
authors: MB
authors: Jekabsons
authors: Ikhlas A
authors: IA
authors: Khan
authors: Dale G
authors: DG
authors: Nagle
authors: Yu-Dong
authors: YD
authors: Zhou
mesh_terms: D028145:Caulophyllum / Q000737:chemistry*; D019069:Cell Respiration / Q000187:drug effects*; D019587:Dietary Supplements / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D008517:Phytotherapy; D012503:Saponins / Q000737:chemistry / Q000633:toxicity*; D014481:United States
chemical_list: D012503:Saponins; C036411:cauloside A; D009828:Oleanolic Acid; C018245:cauloside C