Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia ; Biochemistry Department, College of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Evid Based Complement Alternat Med. 2015;2015:247357. doi: 10.1155/2015/247357. Epub 2015 Apr 6.
Previous data indicated the protective effect of date fruit extract on oxidative damage in rat liver. However, the hepatoprotective effects via other mechanisms have not been investigated. This study was performed to evaluate the antifibrotic effect of date flesh extract (DFE) or date pits extract (DPE) via inactivation of hepatic stellate cells (HSCs), reducing the levels of inflammatory, fibrotic and angiogenic markers. Coffee was used as reference hepatoprotective agent. Liver fibrosis was induced by injection of CCl4 (0.4 mL/kg) three times weekly for 8 weeks. DFE, DPE (6 mL/kg), coffee (300 mg/kg), and combination of coffee + DFE and coffee + DPE were given to CCl4-intoxicated rats daily for 8 weeks. DFE, DPE, and their combination with coffee attenuated the elevated levels of inflammatory cytokines including tumor necrosis factor-α, interleukin-6, and interleukin-1β. The increased levels of transforming growth factor-β1 and collagen deposition in injured liver were alleviated by both extracts. CCl4-induced expression of α-smooth muscle actin was suppressed indicating HSCs inactivation. Increased angiogenesis was ameliorated as revealed by reduced levels and expression of vascular endothelial growth factor and CD31. We concluded that DFE or DPE could protect liver via different mechanisms. The combination of coffee with DFE or DPE may enhance its antifibrotic effects.
先前的数据表明，枣果提取物对大鼠肝脏的氧化损伤具有保护作用。然而，其通过其他机制发挥的护肝作用尚未得到研究。本研究旨在通过肝星状细胞（HSCs）失活、降低炎症、纤维化和血管生成标志物水平，评估枣果肉提取物（DFE）或枣核提取物（DPE）的抗纤维化作用。咖啡被用作参考的护肝剂。通过每周三次向大鼠注射 0.4 mL/kg 的 CCl4 诱导肝纤维化，共 8 周。在 8 周内，将 DFE、DPE（6 mL/kg）、咖啡（300 mg/kg）以及咖啡+DFE 和咖啡+DPE 的组合分别给予 CCl4 中毒大鼠。DFE、DPE 及其与咖啡的组合可减轻包括肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β在内的炎症细胞因子水平的升高。两种提取物均可减轻损伤肝脏中转化生长因子-β1 和胶原蛋白沉积的增加。CCl4 诱导的α-平滑肌肌动蛋白表达抑制表明 HSCs 失活。血管内皮生长因子和 CD31 水平和表达的降低表明血管生成得到改善。我们的结论是，DFE 或 DPE 可通过不同的机制保护肝脏。咖啡与 DFE 或 DPE 的联合使用可能会增强其抗纤维化作用。
