Institute of Clinical Pharmacology, Anhui Medical University, Anhui Province, P.R. China.
Int J Mol Med. 2012 Mar;29(3):491-8. doi: 10.3892/ijmm.2011.844. Epub 2011 Nov 21.
Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract prepared from the roots of Paeonia lactiflora and Astragalus membranaceus (PAE) demonstrated better hepatoprotective activity than the herbs used individually as shown in our previous studies. This study was carried out to investigate the effects of PAE on liver fibrosis induced by porcine serum (PS) in rats and to explore its possible mechanisms. Liver fibrosis was induced in male Wistar rats by injection with PS intraperitoneally. The rats were randomly divided into a normal control group, a liver fibrosis model group and a PAE (40, 80, 160 mg•kg-1) treated group. After a 16-week treatment, PAE-treated rats showed significantly reduced liver damage and symptoms of liver fibrosis upon pathological examination. Administration of PAE significantly decreased serum HA, PC III levels, and content of hydroxyproline in the liver tissue of fibrotic rats. It also restored the decrease in SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during PS treatment. In vitro, PAE also significantly decreased [3H]-thymidine incorporation in hepatic stellate cells (HSCs) stimulated with platelet-derived growth factor-B subunit homodimer (PDGF-BB). Moreover, PAE significantly decreased the expression of PDGF receptor beta (PDGFR-β) and p-ERK1/2, p-p38, p-JNK. The results showed that PAE displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its ability to scavenge free radicals, decreasing the expression of PDGFR-β, inhibition of HSC proliferation and MAPK activation. These findings indicate that PAE is a potential agent for the prevention of liver fibrosis.
白芍和黄芪是两种常用的传统中药，常用于中药方剂治疗肝病。我们之前的研究表明，白芍和黄芪根提取物（PAE）比单独使用草药具有更好的保肝活性。本研究旨在探讨 PAE 对猪血清（PS）诱导的大鼠肝纤维化的影响及其可能的机制。雄性 Wistar 大鼠通过腹腔注射 PS 诱导肝纤维化。大鼠随机分为正常对照组、肝纤维化模型组和 PAE（40、80、160mg•kg-1）治疗组。经过 16 周的治疗，PAE 治疗组大鼠的肝损伤和肝纤维化症状明显减轻。PAE 可显著降低肝纤维化大鼠血清透明质酸（HA）、Ⅲ型前胶原（PC III）水平和肝组织羟脯氨酸含量。它还恢复了 PS 处理过程中 SOD 和 GSH-Px 活性的降低，并抑制了脂质过氧化产物的形成。在体外，PAE 还显著降低了血小板衍生生长因子-B 亚单位同二聚体（PDGF-BB）刺激的肝星状细胞（HSCs）中[3H]-胸苷的掺入。此外，PAE 还显著降低了 PDGF 受体β（PDGFR-β）和 p-ERK1/2、p-p38、p-JNK 的表达。结果表明，PAE 对 PS 诱导的大鼠具有抗纤维化作用，其机制可能与其清除自由基、降低 PDGFR-β表达、抑制 HSC 增殖和 MAPK 激活的能力有关。这些发现表明，PAE 是预防肝纤维化的潜在药物。
