Molecules 2014, 19(2), 1576-1591; doi:10.3390/molecules19021576
Article

Ursolic Acid-Enriched Herba Cynomorii Extract Induces Mitochondrial Uncoupling and Glutathione Redox Cycling Through Mitochondrial Reactive Oxygen Species Generation: Protection Against Menadione Cytotoxicity in H9c2 Cells

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Received: 2 December 2013; in revised form: 19 January 2014 / Accepted: 21 January 2014 / Published: 27 January 2014
(This article belongs to the Special Issue Natural Antioxidants and Ageing)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used ‘Yang-invigorating’ tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.
Keywords: Cynomorium songaricum; ursolic acid; mitochondrial uncoupling; glutathione redox cycling; oxidant injury
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MDPI and ACS Style

Chen, J.; Wong, H.S.; Ko, K.M. Ursolic Acid-Enriched Herba Cynomorii Extract Induces Mitochondrial Uncoupling and Glutathione Redox Cycling Through Mitochondrial Reactive Oxygen Species Generation: Protection Against Menadione Cytotoxicity in H9c2 Cells. Molecules 2014, 19, 1576-1591.

AMA Style

Chen J, Wong HS, Ko KM. Ursolic Acid-Enriched Herba Cynomorii Extract Induces Mitochondrial Uncoupling and Glutathione Redox Cycling Through Mitochondrial Reactive Oxygen Species Generation: Protection Against Menadione Cytotoxicity in H9c2 Cells. Molecules. 2014; 19(2):1576-1591.

Chicago/Turabian Style

Chen, Jihang; Wong, Hoi S.; Ko, Kam M. 2014. "Ursolic Acid-Enriched Herba Cynomorii Extract Induces Mitochondrial Uncoupling and Glutathione Redox Cycling Through Mitochondrial Reactive Oxygen Species Generation: Protection Against Menadione Cytotoxicity in H9c2 Cells." Molecules 19, no. 2: 1576-1591.

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