Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Phytother Res. 2021 Jun;35(6):3365-3376. doi: 10.1002/ptr.7056. Epub 2021 Feb 23.
Morus nigra is a rich source of anthocyanins, phytochemicals that have anticancer effects. This study aimed to investigate the effects of M. nigra extract (MNE) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Male Sprague-Dawley rats were assigned into four groups (n = 10): control, DEN, and DEN +100 or 400 mg/kg of MNE. After 4 months, the DEN group showed a significant mortality rate, hepatic lipid peroxidation, dysplastic nodules in the cirrhotic liver, and an increase of blood bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Also, the body weight gain, blood albumin and glucose, liver antioxidant capacity (thiol groups), and some hematological parameters (RBC, hematocrit, hemoglobin, and platelet) were significantly decreased in the DEN group. MNE significantly increased survival, reduced the size of HCC nodules, improved liver oxidant/antioxidant status, and prevented the above-mentioned changes in the blood (except ALP, glucose, and platelet). Quantitative real-time PCR showed that MNE decreased the expression of Wnt4 and β-catenin, while had no significant effect on PI3K, Akt, and PTEN expression. The MNE did not exhibit antiproliferative activity against HepG2 liver cancer cells. In conclusion, MNE exhibits a hepatoprotective effect through inhibiting oxidative stress and Wnt4/β-catenin pathway and therefore prolongs the survival of rats with HCC.
桑椹是花色苷的丰富来源，花色苷具有抗癌作用。本研究旨在探讨桑椹提取物（MNE）对二乙基亚硝胺（DEN）诱导的肝细胞癌（HCC）的影响。雄性 Sprague-Dawley 大鼠分为四组（n=10）：对照组、DEN 组、DEN+100 或 400mg/kg MNE 组。4 个月后，DEN 组死亡率显著升高，肝脂质过氧化，肝硬化中出现发育不良结节，胆红素、天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和碱性磷酸酶（ALP）升高。此外，DEN 组大鼠体重增加、血液白蛋白和葡萄糖、肝脏抗氧化能力（巯基基团）以及一些血液学参数（RBC、血细胞比容、血红蛋白和血小板）显著降低。MNE 显著提高了生存率，减小了 HCC 结节的大小，改善了肝脏的氧化应激/抗氧化状态，并防止了血液中发生上述变化（除 ALP、葡萄糖和血小板外）。实时定量 PCR 显示，MNE 降低了 Wnt4 和 β-连环蛋白的表达，但对 PI3K、Akt 和 PTEN 的表达没有显著影响。MNE 对 HepG2 肝癌细胞没有明显的抗增殖活性。综上所述，MNE 通过抑制氧化应激和 Wnt4/β-连环蛋白通路发挥肝保护作用，从而延长 HCC 大鼠的生存时间。
