Badr Gamal, Sayed Eman Abdo, Waly Hanan, Hassan Khadiga Abdel-Hameed, Mahmoud Mohamed H, Selamoglu Zeliha
Zoology Department, Faculty of Science, Assiut University, Assiut, Egypt.
Laboratory of Immunology, Zoology Department, Faculty of Science, Assiut, Egypt.
Cell Physiol Biochem. 2019;53(2):301-322. doi: 10.33594/000000140.
BACKGROUND/AIMS: Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl-mediated liver fibrosis.
Three groups of male BALB/c mice (n=15/ group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA.
We found that the induction of liver fibrosis by CCl was associated with a significant increase in hepatic collagen and α-smooth muscle actin (α-SMA) expression. Moreover, CCl-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-β followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice.
Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis.
背景/目的：蜂胶是最具前景的天然产物之一，不仅具有治疗作用，还具有预防作用。蜂胶具有多种生物学和药理学特性，包括肝脏保护活性。本研究旨在探讨蜂胶抗四氯化碳介导的肝纤维化的潜在分子机制。
使用三组雄性BALB/c小鼠（每组n = 15）：第1组为对照小鼠；第2组和第3组注射四氯化碳以诱导肝纤维化。然后第3组口服补充蜂胶（100 mg/kg体重），持续四周。采用不同技术监测蜂胶的抗纤维化作用，包括使用苏木精和伊红、Masson三色染色和天狼星红染色进行组织病理学研究；蛋白质免疫印迹法；流式细胞术；以及酶联免疫吸附测定法。
我们发现，四氯化碳诱导的肝纤维化与肝脏胶原蛋白和α平滑肌肌动蛋白（α-SMA）表达的显著增加有关。此外，四氯化碳处理的小鼠肝脏结构也出现了组织病理学改变。此外，四氯化碳处理的小鼠肝脏促炎信号明显增加，如热休克蛋白70表达增加、促炎细胞因子和活性氧水平升高。从机制上讲，四氯化碳处理的小鼠肝脏中AKT和mTOR的磷酸化显著增加；BAX和细胞色素C的表达上调；Bcl2的表达下调；转化生长因子-β水平显著升高，随后SMAD2磷酸化增加；P53和诱导型一氧化氮合酶的表达显著增加。有趣的是，给四氯化碳处理的小鼠口服补充蜂胶可显著消除肝脏胶原蛋白沉积，消除炎症信号和氧化应激，恢复四氯化碳介导的信号级联变化，从而使肝脏结构几乎恢复到对照小鼠中观察到的正常结构。
我们的研究结果揭示了蜂胶抗肝纤维化的治疗潜力及其潜在机制。
