School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China.
Eur J Pharmacol. 2012 Apr 5;680(1-3):95-101. doi: 10.1016/j.ejphar.2012.01.010. Epub 2012 Jan 28.
Baicalin has been reported to protect against liver injury in iron-overload mice, however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In this study, we systematically studied the protective effect of baicalin on iron overload induced liver injury, as well as the underlying mechanism based on nitrative stress in rat model. We found that when iron overload rats (500mgiron/kg) were fed baicalin-containing diet (0.3% and 1% w/w) for 45days, baicalin dose dependently protected against iron overload induced liver injury, including alleviation of hepatic pathological damage, decrease of SOD activity, iron content, carbonyl content, and the thiobarbituric acid-reactive substances level in hepatic tissues. It also increased serum iron content, SH content and GPx activity, decreased serum ALT and AST activities. Immunohistochemistry and immunoprecipitation analysis revealed that baicalin could also inhibit iron overload induced protein tyrosine nitration in liver. Moreover, in iron overload rat liver, we found that baicalin decreased the iron overload increased level of glutathione-S-transferases (GSTs) expression, oxidation and nitration. These results suggest that not only oxidative stress, but also nitrative stress, is involved in iron overload induced liver injury, and the underlying mechanism might partially relate to the involvement of GSTs expression and post-translational modification. Baicalin can effectively prevent iron overload caused abnormality and can be a candidate medicine for iron overload diseases.
黄芩苷已被报道可防止铁过载小鼠的肝损伤，然而，黄芩苷对肝脏的保护作用的机制尚未完全了解。在本研究中，我们基于铁过载大鼠模型中的硝化应激，系统研究了黄芩苷对铁过载诱导的肝损伤的保护作用及其潜在机制。我们发现，当铁过载大鼠（500mgiron/kg）喂食含黄芩苷的饮食（0.3%和 1%w/w）45 天时，黄芩苷呈剂量依赖性地防止铁过载诱导的肝损伤，包括减轻肝组织病理损伤、降低 SOD 活性、铁含量、羰基含量和肝组织中的硫代巴比妥酸反应物质水平。它还增加了血清铁含量、SH 含量和 GPx 活性，降低了血清 ALT 和 AST 活性。免疫组织化学和免疫沉淀分析表明，黄芩苷还可以抑制肝内铁过载诱导的蛋白质酪氨酸硝化。此外，在铁过载大鼠肝脏中，我们发现黄芩苷降低了铁过载增加的谷胱甘肽-S-转移酶（GSTs）表达、氧化和硝化水平。这些结果表明，铁过载诱导的肝损伤不仅涉及氧化应激，还涉及硝化应激，其潜在机制可能部分与 GSTs 表达和翻译后修饰有关。黄芩苷能有效预防铁过载引起的异常，可作为铁过载疾病的候选药物。
