Department of Biochemistry, Laboratory of Liver Metabolism, University of Maringá, 87020900 Maringá, Brazil.
Toxicol Appl Pharmacol. 2011 Dec 15;257(3):319-27. doi: 10.1016/j.taap.2011.09.004. Epub 2011 Sep 16.
Juglone is a phenolic compound used in popular medicine as a phytotherapic to treat inflammatory and infectious diseases. However, it also acts as an uncoupler of oxidative phosphorylation in isolated liver mitochondria and, thus, may interfere with the hepatic energy metabolism. The purpose of this work was to evaluate the effect of juglone on several metabolic parameters in the isolated perfused rat liver. Juglone, in the concentration range of 5 to 50μM, stimulated glycogenolysis, glycolysis and oxygen uptake. Gluconeogenesis from both lactate and alanine was inhibited with half-maximal effects at the concentrations of 14.9 and 15.7μM, respectively. The overall alanine transformation was increased by juglone, as indicated by the stimulated release of ammonia, urea, l-glutamate, lactate and pyruvate. A great increase (9-fold) in the tissue content of α-ketoglutarate was found, without a similar change in the l-glutamate content. The tissue contents of ATP were decreased, but those of ADP and AMP were increased. Experiments with isolated mitochondria fully confirmed previous notions about the uncoupling action of juglone. It can be concluded that juglone is active on metabolism at relatively low concentrations. In this particular it resembles more closely the classical uncoupler 2,4-dinitrophenol. Ingestion of high doses of juglone, thus, presents the same risks as the ingestion of 2,4-dinitrophenol which comprise excessive compromising of ATP production, hyperthermia and even death. Low doses, i.e., moderate consumption of natural products containing juglone, however, could be beneficial to health if one considers recent reports about the consequences of chronic mild uncoupling.
胡桃醌是一种酚类化合物，在民间医学中被用作植物疗法来治疗炎症和传染病。然而，它也作为一种解偶联剂在分离的肝线粒体中起作用，因此可能会干扰肝的能量代谢。本工作的目的是评价胡桃醌对分离的大鼠肝灌注中的几个代谢参数的影响。胡桃醌在 5 至 50μM 的浓度范围内刺激糖原分解、糖酵解和耗氧量。来自乳酸和丙氨酸的糖异生分别在 14.9 和 15.7μM 的浓度下被抑制至半最大效应。胡桃醌增加了整体的丙氨酸转化，这表明氨、尿素、L-谷氨酸、乳酸和丙酮酸的释放被刺激。发现组织中α-酮戊二酸的含量大大增加（9 倍），而 L-谷氨酸的含量没有类似的变化。组织中 ATP 的含量减少，但 ADP 和 AMP 的含量增加。与分离的线粒体进行的实验完全证实了先前关于胡桃醌解偶联作用的概念。可以得出结论，胡桃醌在相对较低的浓度下对代谢有活性。在这方面，它更类似于经典的解偶联剂 2,4-二硝基苯酚。因此，摄入高剂量的胡桃醌与摄入 2,4-二硝基苯酚一样，存在着过度消耗 ATP 产生、体温过高甚至死亡的风险。然而，如果考虑到关于慢性轻度解偶联的后果的最新报告，低剂量，即适度消耗含有胡桃醌的天然产物，可能对健康有益。
