A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Artemisia annua on the Treatment of Hepatocellular Carcinoma

Abstract

Objective. To investigate the potential active ingredients and underlying mechanisms of Artemisia annua (AA) on the treatment of hepatocellular carcinoma (HCC) based on network pharmacology. Methods. In the present study, we used a network pharmacological method to predict its underlying complex mechanism of treating HCC. First, we obtained relative compounds of AA based on the traditional Chinese medicine systems pharmacology (TCMSP) database and collected potential targets of these compounds by target fishing. Then, we built HCC-related targets target by the oncogenomic database of hepatocellular carcinoma (OncoDB.HCC) and biopharmacological network (PharmDB-K) database. Based on the matching results between AA potential targets and HCC targets, we built a protein-protein interaction (PPI) network to analyze the interactions among these targets and screen the hub targets by topology. Furthermore, the function annotation and signaling pathways of key targets were performed by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking. Results. A total of 19 main active ingredients of AA were screened as target prediction; then, 25 HCC-related common targets were seeked out via multiple HCC databases. The areas of nodes and corresponding degree values of EGFR, ESR1, CCND1, MYC, EGF, and PTGS2 were larger and could be easily found in the PPI network. Furthermore, GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis to accomplish the anti-HCC activity. The molecular docking analysis showed that quercetin could stably bind to the active pocket of EGFR protein 4RJ5 via LibDock. Conclusion. The anticancer effects of AA on HCC were predicted to be associated with regulating tumor cell proliferation, apoptosis, angiogenesis, tumor invasion, and metastasis via various pathways such as the EGFR signaling pathway, ESR1 signaling pathway, and CCND1 signaling pathway. It is suggested that AA might be developed as a broad-spectrum antitumor drug based on its characteristics of multicomponent, multipath, and multitarget.

Identification of the active compounds and their mechanisms of medicinal and edible Shanzha based on network pharmacology and molecular docking

“…Besides, when it is activated by upstream signals, PI3K indirectly regulates cell proliferation and survival by phosphorylation of MTOR protein through signaling pathway cascade (Aoki & Fujishita, 2017). In addition, PI3K is strongly associated with inflammation (Aoki & Fujishita, 2017; Zhang M. M. et al., 2021; Zhang S. et al., 2021; Zhang S. W. et al., 2021). Related studies found that MMP9 could play critical roles in many biological processes, such as reproduction, host defenses, cell proliferation and differentiation.…”

“…TNF is a target in TNF signaling pathway and is associated with inflammation (Chattopadhyay et al., 2021). HSP90AA1 is a protein‐coding gene and is overexpressed in colon cancers (Zhang M. M. et al., 2021; Zhang S. et al., 2021; Zhang S. W. et al., 2021). Estrogen promotes nNOS activation via G protein‐coupled ESR1 and increases NO to inhibit colon movement in the estrogen signaling pathway (Li et al., 2015).…”

“…The data were stored in a tab‐separated value format and uploaded into the Cytoscape 3.8.2 software where the PPI was drawn and analyzed. The freedom degree, betweenness, and closeness of lapped genes were the three main parameters for critical target screening (Zhang M. M. et al., 2021; Zhang S. et al., 2021; Zhang S. W. et al., 2021). The screened key targets could draw the hub network according to the over average betweenness centrality, closeness centrality and a double of average freedom degree.…”

Structural Characterization and In-Vitro Antioxidant and Immunomodulatory Activities of Polysaccharide Fractions Isolated from Artemisia annua L.

“…Traditionally, Artemisia annua (Asteraceae) is an alternative source of nutrients for humans and livestock and is found in the northern parts of China [ 3 ]. The stems were also traditionally used in Chinese medicine for preventing malaria and enhancing immunity in patients [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. A. annua also displayed anticancer activities against various tumors in vitro and in vivo, as well as exhibiting significant synergistic effects with several clinical anti-tumor medicines [ 6 , 12 ].…”

“…The stems were also traditionally used in Chinese medicine for preventing malaria and enhancing immunity in patients [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. A. annua also displayed anticancer activities against various tumors in vitro and in vivo, as well as exhibiting significant synergistic effects with several clinical anti-tumor medicines [ 6 , 12 ]. Several bioactive compounds have been isolated from A. annua , which include sesquiterpenoids, flavonoids, coumarins, triterpenoids, steroids, phenolics, purines and lipids [ 7 , 13 , 14 , 15 , 16 , 17 , 18 ].…”