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.
J Nat Prod. 2014 Jan 24;77(1):111-7. doi: 10.1021/np400758t. Epub 2013 Dec 11.
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.
某些植物性膳食补充剂与特发性器官特异性毒性有关。由于药物引起的线粒体功能障碍而导致的类似毒理学事件，迫使主要药物被撤回或美国食品和药物管理局（FDA）发布“黑框”警告。为了评估植物性膳食补充剂的潜在线粒体毒性，评估了来自 352 种经鉴定的植物样本的提取物，以评估其破坏细胞呼吸的能力。蓝升麻（Caulophyllum thalictroides）甲醇提取物表现出线粒体毒性活性。蓝升麻被一些美国助产士用来帮助引产，与围产期中风、急性心肌梗死、充血性心力衰竭、多器官损伤和新生儿休克有关。线粒体破坏与特发性草药中毒之间的潜在联系促使进一步检查。C. thalictroides 甲醇提取物和三种皂苷，即 cauloside A（1）、saponin PE（2）和 cauloside C（3），表现出浓度和时间依赖性的线粒体毒性活性。在治疗后，细胞呼吸速率迅速增加，然后在几分钟内急剧下降。机制研究表明，C. thalictroides 成分通过破坏膜完整性来损害线粒体功能。这些研究为这种线粒体敏感型细胞毒性与特发性器官损伤之间提供了潜在的病因学联系。
