Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Biomed Pharmacother. 2018 May;101:49-57. doi: 10.1016/j.biopha.2018.02.064. Epub 2018 Feb 22.
Lysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis.
Hepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks. Silymarin (50 mg/kg), caffeine (50 mg/kg), and their combination (50 mg/kg silymarin + 50 mg/kg caffeine) were orally given to rats every day for 8 weeks along with TAA injection. Liver functions were measured. Histopathological examination of liver tissues was performed using hematoxylin and eosin and Masson's trichrome staining. mRNA expressions of LPAR1, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), and alpha smooth muscle actin (α-SMA) were measured using RT-PCR. LPAR1 tissue expression was scored using immunohistochemistry.
Silymarin, caffeine, and their combination significantly improved liver function. They caused significant decrease in fibrosis and necro-inflammatory scores. Combination of silymain and caffeine caused a significant decrease in the necro-inflammatory score than the single treatment with silymarin or caffeine. In addition, silymarin, caffeine, and their combination significantly decreased hepatic LPAR1, TGF-β1, CTGF, and α-SMA gene expressions and LPAR1 tissue expression.
Silymarin, caffeine, and their combination protect against liver fibrosis through down-regulation of LPAR1, TGF-β1, and CTGF.
溶血磷脂酸是一种脂质介质，据推测与肝纤维化有关。水飞蓟素和咖啡因是具有抗炎和抗氧化作用的天然化合物。我们的研究旨在探讨水飞蓟素、咖啡因及其组合对硫代乙酰胺（TAA）诱导的肝纤维化中溶血磷脂酸受体 1（LPAR1）途径的影响。
雄性 Sprague-Dawley 大鼠通过腹腔注射 200mg/kg TAA 每周两次，共 8 周诱导肝纤维化。水飞蓟素（50mg/kg）、咖啡因（50mg/kg）及其组合（50mg/kg 水飞蓟素+50mg/kg 咖啡因）在 TAA 注射的同时每天给予大鼠口服 8 周。测量肝功能。使用苏木精和伊红以及 Masson 三色染色对肝组织进行组织病理学检查。使用 RT-PCR 测量 LPAR1、转化生长因子-β1（TGF-β1）、结缔组织生长因子（CTGF）和α平滑肌肌动蛋白（α-SMA）的 mRNA 表达。使用免疫组织化学对 LPAR1 组织表达进行评分。
水飞蓟素、咖啡因及其组合显著改善肝功能。它们导致纤维化和坏死性炎症评分显著降低。与水飞蓟素或咖啡因单一治疗相比，水飞蓟素和咖啡因联合使用导致坏死性炎症评分显著降低。此外，水飞蓟素、咖啡因及其组合显著降低肝 LPAR1、TGF-β1、CTGF 和 α-SMA 基因表达和 LPAR1 组织表达。
水飞蓟素、咖啡因及其组合通过下调 LPAR1、TGF-β1 和 CTGF 来保护肝脏免受纤维化的影响。
