Assessing the Potential Mitochondrial-Mediated Toxicity of Herbal Dietary Supplements

DG Nagle; F Mahdi; S Datta; J Li; L Du; TJ Smillie; IA Khan; MB Jekabsons; YD Zhou

doi:10.1055/s-0031-1273513

Planta Medica, Table of Contents

Assessing the Potential Mitochondrial-Mediated Toxicity of Herbal Dietary Supplements

DG Nagle ¹, F Mahdi ¹, S Datta ¹, J Li ¹, L Du ¹, TJ Smillie ², IA Khan ¹^,²^,³, MB Jekabsons ⁴, YD Zhou ¹

¹Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi, 38677, USA
²National Center for Natural Products Research, and the Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi, 38677, USA
³Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
⁴Department of Biology, University of Mississippi, University, Mississippi, 38677, USA

Abstract

Drug-induced mitochondrial dysfunction has recently become recognized to dramatically limit the development or use of modern pharmaceuticals [1,2]. Mitochondrial-mediated hepatic and cardiovascular toxicity has forced the recent withdrawal of major drugs used to treat diabetes (troglitazone) and hyperlipidemia (cerivastatin). Approximately 50% of the drugs with FDA Black Box Warnings for hepatoxicity and cardiovacular toxicity are known to interfere with mitochondrial function. The pharmaceutical industry has only recently realized the critical importance of implementing measures to assess the potential mitochondrial toxicity of new drug leads early in the development process [1,2]. No such methods have been rigorously applied to the ingredients widely consumed in the form of herbal dietary supplements. Extracts from more than 350 species of plants and other organisms used in traditional Chinese, Indian, African, and Western herbal medicine were evaluated for their ability to disrupt mitochondrial function. Extracts from 15 different plant species suppressed mitochondrial respiration in mammalian cells. Nine other species weakly interfered with cellular respiration. Extracts from five species potently uncoupled oxidative phosphorylation. Several species possess compounds that have been demonstrated to interfere with mitochondrial function (i.e., Chenopodium botrys, Commiphora mukul, Larrea tridentata, and Tripterygium wilfordii). Some of these species have been associated with severe toxicity to the liver (i.e., L. tridentate, T. wilfordii) or heart (T. wilfordii) in certain patients. However, these studies indicate that a much larger number of plant extracts contain components that induce mitochondrial dysfunction and may be responsible for various forms of long-term or potential idiosyncratic mitochondrial-mediated toxicities.

Acknowledgements: This research was supported by NIH Grant CA98787, NOAA/NIUST Grant NA16RU1496, and conducted in a facility constructed with NIH Research Facilities Improvement Grant C06 RR-14503–01.

References: [1] Dykens JA, Will Y, (2007) Drug Disc Today, 12: 777–785. [2] Dykens JA, Will Y, (2010) International Drug Disc, 5: 32–36.