A network pharmacology-based study on the anti-hepatoma effect of Radix Salviae Miltiorrhizae

Yi Luo,Yu-Jie Huang,Sha-Sha Bai,Qi Wang,Hong-Lian Shi,Yu Feng,Ming Hong,Sha Li,Mohammed M Almutairi,Lei Song,Si-Ying Li,Gan-Qing He

doi:10.1186/s13020-019-0249-6

Abstract

BackgroundRadix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. However, the anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated.MethodsIn this study, we aimed to elucidate the underlying molecular mechanisms of RSM in the treatment of HCC using a network pharmacology approach. In vivo and in vitro experiments were also performed to validate the therapeutic effects of RSM on HCC.ResultsIn total, 62 active compounds from RSM and 72 HCC-related targets were identified through network pharmacological analysis. RSM was found to play a critical role in HCC via multiple targets and pathways, especially the EGFR and PI3K/AKT signaling pathways. In addition, RSM was found to suppress HCC cell proliferation, and impair cancer cell migration and invasion in vitro. Flow cytometry analysis revealed that RSM induced cell cycle G2/M arrest and apoptosis, and western blot analysis showed that RSM up-regulated the expression of BAX and down-regulated the expression of Bcl-2 in MHCC97-H and HepG2 cells. Furthermore, RSM administration down-regulated the expression of EGFR, PI3K, and p-AKT proteins, whereas the total AKT level was not altered. Finally, the results of our in vivo experiments confirmed the therapeutic effects of RSM on HCC in nude mice.ConclusionsWe provide an integrative network pharmacology approach, in combination with in vitro and in vivo experiments, to illustrate the underlying therapeutic mechanisms of RSM action on HCC.

Highlights

Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers
Chemical composition and targets of RSM In total, 202 compounds were collected from RSM
The results demonstrated that 68 targets were mapped into the 99 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including pathways in cancer, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, and proteoglycans in cancer, while four of 72 targets were not mapped into pathways

Summary

Introduction

Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicine, has been shown to inhibit tumorigenesis in various human cancers. The anticancer effects of RSM on human hepatocellular carcinoma (HCC) and the underlying mechanisms of action remain to be fully elucidated. Bae et al [14] showed that S. miltiorrhiza Bunge might present a significant anticancer effect by inhibiting prostate cancer cell proliferation and inducing prostate cancer cell apoptosis. Previous studies have shown that TIIA is an active component of RSM, which inhibits human gastric cancer cells by decreasing HER2 and VEGFR protein levels, inhibits the Ras/Raf/MEK/ERK signaling pathway, and induces caspase-3, PARP activation, and apoptosis [16]. RSM and its active components may serve as a promising anti-cancer therapy; its pharmacological mechanisms of action have not been fully elucidated. The aim of our research was to explore the anti-HCC effects of RSM extracts and explore the underlying mechanisms

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