Guangxi Medical University, Nanning 530021, China.
The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
Fitoterapia. 2014 Jun;95:203-13. doi: 10.1016/j.fitote.2014.03.020. Epub 2014 Apr 2.
A compound was isolated from Centipeda minima using bioassay-guided screening. The structure of this compound was elucidated based on its spectral data, and it was identified as helenalin. The hepatoprotective effect of helenalin was evaluated using a liver fibrosis model induced by intragastric administration with alcohol within 24 weeks in rats. The results revealed that helenalin significantly prevented alcohol-induced hepatic injury and fibrogenesis, as evidenced by the decrease in serum aminotransferase, the attenuation of histopathological changes, and the inhibition of the hepatic fibrosis indicators, such as hyaluronic acid, type III precollagen, laminin, hydroxyproline and collagen α type I. Mechanistically, studies showed that helenalin expedited ethanol metabolism by enhancing the alcohol and aldehyde dehydrogenase activities. Furthermore, helenalin alleviated lipid peroxidation, recruited the antioxidative defense system, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TGF-β1, TNF-α, IL-6 and IL-1β and myeloperoxidase, via down-regulation of NF-κB. Helenalin significantly decreased collagen deposition by reducing the profibrotic cytokines like transforming growth factor-β, platelet-derived growth factor-β and connective tissue growth factor, and promoted extracellular matrix degradation by modulating the levels of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9. In addition, helenalin inhibited HSC activation as evidenced by the down-regulation of α-SMA and TGF-β levels. In conclusion, helenalin had a significant protective effect on chronic ethanol-induced hepatic fibrosis and may be a major bioactive ingredient of C. minima.
从细梗香草中采用生物活性导向筛选法分离得到一种化合物。根据其光谱数据阐明了该化合物的结构，并鉴定为秦皮乙素。通过在大鼠体内 24 周内胃内给予酒精诱导的肝纤维化模型，评估了秦皮乙素的保肝作用。结果表明，秦皮乙素可显著预防酒精引起的肝损伤和纤维化，其血清转氨酶降低，组织病理学变化减轻，肝纤维化指标如透明质酸、III 型前胶原、层粘连蛋白、羟脯氨酸和胶原α型 I 得到抑制。机制研究表明，秦皮乙素通过增强醇脱氢酶和醛脱氢酶的活性来加速乙醇代谢。此外，秦皮乙素通过减轻脂质过氧化、募集抗氧化防御系统、抑制 CYP2E1 活性、降低 TGF-β1、TNF-α、IL-6 和 IL-1β 等炎症介质和髓过氧化物酶，减轻 NF-κB 的下调，从而缓解肝纤维化。秦皮乙素通过降低促纤维化细胞因子如转化生长因子-β、血小板衍生生长因子-β和结缔组织生长因子的水平，减少胶原沉积，并通过调节组织抑制剂 1 和基质金属蛋白酶-9 的水平，促进细胞外基质的降解。此外，秦皮乙素抑制 HSC 活化，下调α-SMA 和 TGF-β 水平。综上所述，秦皮乙素对慢性乙醇诱导的肝纤维化具有显著的保护作用，可能是细梗香草的主要生物活性成分。
