Laboratory of Experimental Hepatology, Department of Pharmacology, Cinvestav-IPN, Av. Instituto Politécnico Nacional, Mexico City, Mexico.
Department of Physiology, Biophysics and Neurosciences, Cinvestav-IPN, Mexico City, Mexico.
Ann Hepatol. 2020 Sep-Oct;19(5):497-506. doi: 10.1016/j.aohep.2020.05.006. Epub 2020 Jul 14.
Curcumin, a polyphenol, is a natural compound that has been widely studied as a hepatoprotector; however, only a few studies have examined its ability to reduce fibrosis in previously established cirrhosis. The objective of this study was to investigate whether curcumin could reduce carbon tetrachloride (CCl)-induced fibrosis and if so, to determine the action mechanisms involved in the reduction process.
CCl was administered to male Wistar rats (400 mg/kg, three times a week, i. p.) for 12 weeks; curcumin (100 mg/kg body weight twice per day, p. o.) was administered from week 9-12 of CCl treatment. Biochemical markers of hepatic injury and oxidative stress were evaluated. Hematoxylin and eosin, Masson's trichrome stains, transmission electron microscopy; immunohistochemistry, and zymography assays were carried out. Moreover, Smad3 and α-SMA mRNA and protein levels were studied. Western blotting by TGF-β, CTGF, Col-I, MMP-13, NF-κB, IL-1, IL-10, Smad7, pSmad3, and pJNK proteins was developed.
Curcumin reduced liver damage, oxidative stress, fibrosis, and restored normal activity of MMP-9 and MMP-2. Besides, curcumin restored NF-κB, IL-1, IL-10, TGF-β, CTGF, Col-I, MMP-13, and Smad7 protein levels. On the other hand, curcumin decreased JNK and Smad3 phosphorylation. Furthermore, curcumin treatment decreased α-SMA and Smad3 protein and mRNA levels. Curcumin normalized GSH, and NF-κB, JNK-Smad3, and TGF-β-Smad3 pathways, leading to a decrement in activated hepatic stellate cells, thereby producing its antifibrotic effects.
姜黄素是一种多酚，是一种天然化合物，已被广泛研究作为一种肝保护剂；然而，只有少数研究检查了其减少先前建立的肝硬化纤维化的能力。本研究的目的是研究姜黄素是否可以减少四氯化碳（CCl）诱导的纤维化，如果可以，确定减少过程中涉及的作用机制。
雄性 Wistar 大鼠（400mg/kg，每周三次，腹腔内注射）给予 CCl 12 周；姜黄素（100mg/kg 体重，每日两次，口服）从 CCl 治疗的第 9-12 周给予。评估肝损伤和氧化应激的生化标志物。进行苏木精和伊红、马松三色染色、透射电子显微镜；免疫组织化学和组织蛋白酶谱分析。此外，还研究了 Smad3 和 α-SMA mRNA 和蛋白水平。通过 TGF-β、CTGF、Col-I、MMP-13、NF-κB、IL-1、IL-10、Smad7、pSmad3 和 pJNK 蛋白进行 Western 印迹。
姜黄素减轻了肝损伤、氧化应激、纤维化，并恢复了 MMP-9 和 MMP-2 的正常活性。此外，姜黄素恢复了 NF-κB、IL-1、IL-10、TGF-β、CTGF、Col-I、MMP-13 和 Smad7 蛋白水平。另一方面，姜黄素降低了 JNK 和 Smad3 的磷酸化。此外，姜黄素处理降低了 α-SMA 和 Smad3 蛋白和 mRNA 水平。姜黄素使 GSH 正常化，以及 NF-κB、JNK-Smad3 和 TGF-β-Smad3 途径，导致活化的肝星状细胞减少，从而产生其抗纤维化作用。
