Department of Biochemistry and Molecular Biology, Medical College of Yanbian University, Yanji, China.
Basic Clin Pharmacol Toxicol. 2009 Dec;105(6):380-6. doi: 10.1111/j.1742-7843.2009.00454.x. Epub 2009 Sep 30.
The protective effect of rossicaside B, the major phenylpropanoid glycoside from Boschniakia rossica, on CCl(4)-induced hepatotoxicity and the mechanisms underlying its protective effect were investigated. The mice were administered orally with rossicaside B (100 or 200 mg/kg of body weight) 48, 24 and 1 hr before CCl(4) (0.5 ml/kg of body weight) administration. The CCl(4) challenge caused a marked increase in the levels of serum aspartate aminotransferase, alanine aminotransferase and of tumour necrosis factor-alpha, and propagated lipid peroxidation with a concomitant reduction in reduced glutathione (GSH) and antioxidative enzyme activities in the liver. The administration of rossicaside B to CCl(4)-treated mice not only decreased the serum toxicity marker enzymes and TNF-alpha but also reduced hepatic oxidative stress, as demonstrated by decreased lipid hydroperoxide and thiobarbituric acid-reactive substance concentrations, combined with elevated GSH content and antioxidative enzyme activities in the liver tissues. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and haem oxygenase-1 (HO-1) were elevated after CCl(4) treatment while the cytochrome P450 2E1 (CYP2E1)-specific monooxygenase activity was suppressed. Rossicaside B treatment inhibited the formation of liver nitrite, reduced the over-expression of iNOS and COX-2 proteins, but increased the CYP2E1 function compared with the CCl(4)-treated mice. However, the protein expression of HO-1 was further elevated by rossicaside B treatment. The results demonstrate that rossicaside B provides a protective action on CCl(4)-induced acute hepatic injury, which may be related to its antioxidative activity, suppressed inflammatory responses, induced HO-1 expression and improved CYP2E1 function in the liver.
从Boschniakia rossica 中提取的主要苯丙素糖苷 rossicaside B 对 CCl(4)诱导的肝毒性的保护作用及其保护作用的机制进行了研究。小鼠在 CCl(4)（0.5 ml/kg 体重）给药前 48、24 和 1 小时分别口服给予 rossicaside B（100 或 200 mg/kg 体重）。CCl(4) 攻击导致血清天冬氨酸转氨酶、丙氨酸转氨酶和肿瘤坏死因子-α水平显著升高，并导致肝脂质过氧化，同时降低还原型谷胱甘肽（GSH）和抗氧化酶活性。将 rossicaside B 给予 CCl(4)处理的小鼠不仅降低了血清毒性标志物酶和 TNF-α，而且还降低了肝氧化应激，如肝组织中脂质氢过氧化物和硫代巴比妥酸反应物质浓度降低，同时 GSH 含量和抗氧化酶活性升高所示。此外，CCl(4)处理后肝内亚硝酸盐、诱导型一氧化氮合酶 (iNOS)、环氧化酶-2 (COX-2) 和血红素加氧酶-1 (HO-1) 的含量升高，而细胞色素 P450 2E1 (CYP2E1)-特异性单加氧酶活性受到抑制。Rossicaside B 处理抑制了肝亚硝酸盐的形成，降低了 iNOS 和 COX-2 蛋白的过表达，但与 CCl(4)处理的小鼠相比，增加了 CYP2E1 功能。然而，HO-1 的蛋白表达进一步被 rossicaside B 处理上调。结果表明，rossicaside B 对 CCl(4)诱导的急性肝损伤具有保护作用，这可能与其抗氧化活性、抑制炎症反应、诱导 HO-1 表达和改善 CYP2E1 功能有关。
