Balta Cornel, Ciceu Alina, Herman Hildegard, Rosu Marcel, Boldura Oana Maria, Hermenean Anca
Institute of Life Sciences, "Vasile Goldis" Western University of Arad, Arad, Romania.
Department of Chemistry, Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Banat University of Agricultural Sciences and Veterinary Medicine "King Mihai I of Romania," Timisoara, Romania.
Dose Response. 2018 Aug 8;16(3):1559325818789835. doi: 10.1177/1559325818789835. eCollection 2018 Jul-Sep.
Liver fibrosis represents an overaccumulation of extracellular matrix (ECM). This study was designed to investigate the effect of chrysin on established ECM overproduction in carbon tetrachloride (CCl) mouse liver fibrosis. Experimental fibrosis was induced by intraperitoneal injection of 2 mL/kg CCl twice a week, for 7 weeks. Mice were orally treated with 3 doses of chrysin (5,7-dihydroxyflavone). For the assessment of the spontaneous reversion of fibrosis, CCl-treated mice were investigated after 2 weeks of recovery time. Silymarin was used as a standard of liver protection. In fibrotic livers, the results showed the upregulation of collagen I (Col I) and tissue inhibitors of metalloproteinase 1 (TIMP-1) and modulation of matrix metalloproteinases (MMPs), which led to an altered ECM enriched in Col, confirmed as well by electron microscopy investigations. Treatment with chrysin significantly reduced ultrastructural changes, downregulated Col I, and restored TIMP-1/MMP balance, whereas in the group observed for the spontaneous regression of fibrosis, they remained in the same pattern with fibrotic livers. In this study, we have shown chrysin efficacy to attenuate dose-dependent CCl-stimulated liver ECM accumulation by regulation of MMP/TIMP imbalance and inhibition of Col production. We have shown the dose-dependent chrysin efficiency in attenuation of CCl4-induced liver ECM accumulation by regulation of MMP/TIMP imbalance and inhibition of Col production. Our findings suggest that chrysin oral administration may introduce a new strategy for treating liver fibrosis in humans.
肝纤维化表现为细胞外基质（ECM）过度蓄积。本研究旨在探讨白杨素对四氯化碳（CCl）诱导的小鼠肝纤维化中已形成的ECM过度产生的影响。通过每周两次腹腔注射2 mL/kg CCl，持续7周诱导实验性纤维化。小鼠口服3种剂量的白杨素（5,7 - 二羟基黄酮）。为评估纤维化的自发逆转，在恢复2周后对CCl处理的小鼠进行研究。水飞蓟宾用作肝脏保护的标准。在纤维化肝脏中，结果显示I型胶原（Col I）和金属蛋白酶组织抑制剂1（TIMP - 1）上调，基质金属蛋白酶（MMPs）发生调节，这导致富含Col的ECM改变，电子显微镜检查也证实了这一点。白杨素治疗显著减少超微结构变化，下调Col I，并恢复TIMP - 1/MMP平衡，而在观察纤维化自发消退的组中，它们与纤维化肝脏保持相同模式。在本研究中，我们已表明白杨素通过调节MMP/TIMP失衡和抑制Col产生，对减轻剂量依赖性CCl刺激的肝脏ECM蓄积有效。我们已表明白杨素通过调节MMP/TIMP失衡和抑制Col产生，在减轻CCl4诱导的肝脏ECM蓄积方面具有剂量依赖性效率。我们的研究结果表明，口服白杨素可能为治疗人类肝纤维化引入一种新策略。
