关键词:

"> 甘遂-甘草药对, 恶性腹水, 网络药理学, 分子对接, PI3K/ AKT1 / MMP9 信号通路

Abstract:

This study aims to explore the mechanism of Kansui Radix-Glycyrrhizae Radix et Rhizoma (KR-GRR) herb pair on malignant ascites (MA) by using network pharmacology and animal experiment. Firstly,the active components of KR-GRR herb pair and the corresponding targets were screened from the TCMSP database. The common targets and signaling pathways of KR-GRR herb pair in treating MA were predicted by network pharmacology,and a protein-protein interaction network was constructed to form a visualized map of Chinese Tradition medicine-components-diseases-targets. GO and KEGG analyses were used to predict the underlying mechanism of KR-GRR herb pair in treating MA. Secondly,molecular docking was employed to obtain the binding ability of the active components of KR-GRR herb pair to the core targets. Finally,the MA mice model was developed using H22 liver cancer cells for the mechanism validation. As a result,network pharmacology results indicated that 13 core bioactive components and 51 potential targets of KR-GRR against MA,with key targets including serine/ threonineprotein kinase 1 (AKT1),tumor necrosis factor (TNF),interleukin- 6 (IL-6),tumor protein 53 (TP53),IL-1β,and Matrix metallopeptidase 9 (MMP9). A total of 141 signaling pathways were screened out by KEGG analysis,and molecular docking results suggested that the PI3K/ AKT1 / MMP9 signaling pathway played a pivotal role in the therapeutic effects of KR-GRR against MA. The animal experiment demonstrated that KR-GRR herb pair significantly improved the general condition,survival rate,and peritoneal histopathological damage in MA mice. Additionally,2. 5 g/ kg of KR-GRR reduced abdominal circumference and ascites volume,and suppressed the expression of AKT1 and MMP9 in ascitic fluid. Furthermore,KR-GRR downregulated the mRNA levels of AKT1,TNF,IL-6,TP53,IL-1β,and MMP9 in peritoneal tissues,as well as the protein expression of p-PI3K,PI3K,p-AKT1,AKT1,and MMP9,especially the ratios of p-PI3K/ PI3K and p-AKT1 / AKT1. Taken together,KRGRR herb pair may exert therapeutic effects against MA by inhibiting the activation of the PI3K/ AKT1 / MMP9 signaling pathway.

Key words:

"> Kansui Radix-Glycyrrhizae Radix et Rhizoma herb pair, malignant ascites, network pharmacology, molecular docking, PI3K/ AKT1 / MMP9 signaling pathway