Fernández-Martínez Eduardo, Bobadilla Rosa A, Morales-Ríos Martha S, Muriel Pablo, Pérez-Alvarez Víctor M
Centro de Investigación en Biología de la Reproducción, Universidad Autónoma del Estado de Hidalgo, Mexico.
Med Chem. 2007 Sep;3(5):475-9. doi: 10.2174/157340607781745410.
Among various phenolic compounds, caffeic acid (3,4-dihydroxycinnamic acid) exhibited pharmacological antioxidant, anticancer and antimutagenic activities. The antioxidant properties of phenolic compounds depend on their chemical structure, however, the role of the ethylenic side chain in the radical scavenging activity remains controversial. Thus, the aim of this study consisted to test cinnamic acid and 15 cinnamic acid derivatives in the well known CCl(4)-induced acute liver damage model, which is dependent on oxidative stress mechanisms. Cinnamic acid and 15 cinnamic acid derivatives (50 mg/kg, p.o.) were administered to male Wistar rats intoxicated with CCl(4) (4 g/kg, p.o.). The activities of gamma-glutamyl transpeptidase, alkaline phosphatase and alanine aminotransferase were measured in serum. The lipid peroxidation products were determined in liver. Compounds with a methoxy group at position 3 or 4, or a 3,4-methylenedioxy moiety were the most active ones. Also, we observed that the monosubstituted 3 or 4 hydroxy, or the bulky 3,4 dibenzyloxy substituted compounds showed lower activity. The poorest activity was displayed by disubstituted 3,4-dihydroxy, dimethoxy or diacetyl cinnamic acid derivatives, the ester derived from cinnamic acid with an 8 carbon chain and N-dimethyl substituted compound. Thus, the methoxy substituted group at positions 3 or 4 or the 3,4-methylenedioxy moiety in the caffeic acid derivatives; seem to be the main features required for the hepatoprotection in this model.
在各种酚类化合物中，咖啡酸（3,4 - 二羟基肉桂酸）具有药理抗氧化、抗癌和抗诱变活性。酚类化合物的抗氧化性能取决于其化学结构，然而，乙烯侧链在自由基清除活性中的作用仍存在争议。因此，本研究的目的是在著名的依赖于氧化应激机制的四氯化碳诱导的急性肝损伤模型中测试肉桂酸和15种肉桂酸衍生物。将肉桂酸和15种肉桂酸衍生物（50毫克/千克，口服）给予用四氯化碳（4克/千克，口服）中毒的雄性Wistar大鼠。测定血清中γ - 谷氨酰转肽酶、碱性磷酸酶和丙氨酸氨基转移酶的活性。测定肝脏中的脂质过氧化产物。在3或4位带有甲氧基或具有3,4 - 亚甲二氧基部分的化合物活性最高。此外，我们观察到单取代的3或4羟基，或庞大的3,4 - 二苄氧基取代的化合物活性较低。二取代的3,4 - 二羟基、二甲氧基或二乙酰基肉桂酸衍生物、具有8个碳链的肉桂酸衍生的酯以及N - 二甲基取代的化合物活性最差。因此，咖啡酸衍生物中3或4位的甲氧基取代基或3,4 - 亚甲二氧基部分；似乎是该模型中肝脏保护所需的主要特征。
