Matrine prevents the early development of hepatocellular carcinoma like lesions in rat liver

Abstract

Matrine (C15H24N2O) is an alkaloid extracted from the Chinese herb Sophora flavescens that has anti-fibrotic and anti-cancer properties. The aim of the present study was to determine the chemopreventive effect of matrine on the development of primary hepatocellular carcinoma (HCC) and its possible association with the suppression of the Notch signaling pathway. The rats were randomly divided into four groups: Control, model, low-dose matrine and high-dose matrine groups. The model was established by combining a partial hepatectomy with diethylnitrosamine (DEN) + 2-acetylaminofluorene (2-AAF). Low-and high-dose matrine groups received intragastric administration of matrine (0.25 and 2.5 g/l of matrine, respectively). DEN + 2-AAF injections and hepatectomy were not performed in the control group. All rats were sacrificed 2, 4 and 7 weeks after hepatectomy. HCC-like histopathological lesions were detected using hematoxylin and eosin staining. The expression levels of α-1-fetoprotein (AFP), albumin (ALB), Notch1 and Hes1 were analyzed using immunohistochemistry. Hepatic lobule structure loss, liver tissue necrosis and inflammatory cell infiltration, and edema degeneration were observed in the model group. By contrast, hepatocyte cord structure was restored and hepatocyte edema degeneration was significantly reduced after 7 weeks of treatment with matrine. In addition, compared with the model group, matrine reduced the expression of AFP, increased the expression of ALB and reduced the expression of Notch1 and Hes1 (only for high-dose matrine; all P<0.05). The findings suggested that matrine could prevent the early development of HCC-like lesions in a rat model, possibly by modulating Notch pathway activation.

Matrine Exerts Pharmacological Effects Through Multiple Signaling Pathways: A Comprehensive Review

“…Matrine acts on tissues and cells through multiple signaling pathways, exerting pharmacological functions such as anti-tumor, anti-inflammatory, and anti-fibrosis. Studies have reported that matrine has a strong inhibitory effect on various tumor cells, and its molecular mechanism lies in regulating cell cycle progression, promoting apoptosis, inhibiting tumor invasion and metastasis, inducing autophagy, reversing multidrug resistance in tumor cells, and regulating metabolism through mediating multiple cellular signaling pathways such as the PI3K/AKT/mTOR, 13–43 NF-κB, 77–85 Wnt/β-catenin, 101–108 MAPKs, 111–118 Notch, 131 , 132 and JAK-STAT 136–138 pathways. Non-coding RNAs also play an important role in these events, 16 , 19 , 22 , 41 , 42 , 102 , 103 , 105 indicating that the anti-tumor mechanisms of matrine involve multi-pathways, multi-targets, and multi-systems.…”

“…Shi et al 132 established a rat model of drug-resistant hepatocyte and further explored the effect of matrine on the early changes of liver carcinogenesis. They indicated that matrine treatment significantly inhibited the development of precancerous lesions, including restoration of hepatic cord structure, reduction of hepatic edema and degeneration, and changes in AFP and ALB expression.…”

Matrine Reverses Multidrug Resistance in Eca-109/VCR Cells Via Inhibiting PI3K/Akt/mTOR Signaling Pathway

“…Although autophagy induction or inhibition has been reported to be implicated in the antitumour activity of matrine against several solid tumours [13,17], the role of autophagy and the underlying mechanism remain unobvious in esophageal carcinoma. MDR is a refractory outcome of chemotherapy and is defned as the resistance of cancer cells to multiple chemotherapeutic drugs with different structures and mechanisms of action [18].…”

Genus Sophora: a comprehensive review on secondary chemical metabolites and their biological aspects from past achievements to future perspectives

“…A combinational treatment of S. moorcroftiana alkaloids with albendazole displayed better therapeutic effects than albendazole alone against liver echinococcosis, and alleviated liver injury (Zhang et al 2018a ). A recent study also suggested that aloperine ( 284 ) could prevent the early development of hepatocellular carcinoma like lesions in rat liver (Shi et al 2019 ).…”