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

Abstract

Background Radix 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. Methods In 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. Results In 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. Conclusions We 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. Electronic supplementary material The online version of this article (10.1186/s13020-019-0249-6) contains supplementary material, which is available to authorized users.

WITHDRAWN: Elucidation of the active compounds and molecular mechanisms of Smilacis Chinae Rhizoma for treatment of pelvic inflammatory disease based on network pharmacology and MMGBSA-docking

“…Recently, network pharmacology has been gradually used in the field of Chinese medicine to investigate the pharmacologic mechanisms [31][32][33]. In this study, network pharmacology was applied to analyze the interaction between SCR and PID and the selection of critical targets.…”

Exploring the Pharmacological Mechanism of Radix Salvia Miltiorrhizae in the Treatment of Radiation Pneumonia by Using Network Pharmacology

“…Radix Salvia Miltiorrhizae (RSM, Danshen in Chinese) is one of the oldest traditional Chinese medicines in China, with a history of more than 1,000 years of clinical application ( 5 , 6 ). RSM has been included in the Chinese Pharmacopoeia since 1963.…”

Analysis and Identification of Active Compounds from Salviae miltiorrhizae Radix Toxic to HCT-116 Human Colon Cancer Cells

“…In the last decade, accumulating evidence has shown that SMR exerts a significant anticancer effect against promyelocytic leukemia, breast cancer, ovarian carcinomas, and hepatocellular carcinoma (HCC) [15][16][17]. In a recent network pharmacology-based study on the anti-HCC effect of SMR, 62 chemical compounds form SMR yielded 101 putative targets that played a critical role in HCC via multiple targets and pathways, especially the EGFR and phosphatidyl-inositol 3-kinase (PI3K)/Akt signaling pathways [18]. However, the effect of SMR and its compounds on human colon cancer cells has not been fully elucidated.…”