Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor without effective therapeutic drugs for most patients in advanced stages. Scutellariae Radix (SR) is a well-known anti-inflammatory and anticarcinogenic herbal medicine. However, the mechanism of SR against HCC remains to be clarified. In the present study, network pharmacology was utilized to characterize the mechanism of SR on HCC. The active components of SR and their targets were collected from the traditional Chinese medicine systems pharmacology database and the traditional Chinese medicine integrated database. HCC-related targets were acquired from the liver cancer databases OncoDB.HCC and Liverome. The gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. Component-component target and protein-protein interaction networks were set up. A total of 143 components of SR were identified, and 37 of them were considered as candidate active components. Fifty targets corresponding to 29 components of SR were mapped with targets of HCC. Functional enrichment analysis indicated that SR exerted an antihepatocarcinoma effect by regulating pathways in cancer, hepatitis B, viral carcinogenesis, and PI3K-Akt signaling. The holistic approach of network pharmacology can provide novel insights into the mechanistic study and therapeutic drug development of SR for HCC treatment.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common and lethal malignancy in the world [1]
All herbal medicinal ingredients of Scutellariae Radix (SR) were obtained from the traditional Chinese medicine systems pharmacology database (TCMSP; http:// tcmspw.com/tcmsp.php) [21], which is a unique analysis platform of systems pharmacology contributing to drug discovery from herbal medicines. e candidate active components of SR were obtained on the basis of the criteria of drug likeness (DL) of ≥0.18 and oral bioavailability (OB) of ≥30%, which are the principal properties to determine the drug ability of compounds
HCC-related genes were retrieved from Liverome [22] and OncoDB.HCC [23], which are two liver cancer-related databases. e drug targets of the candidate active components of SR were mapped to HCCrelated targets to obtain the candidate targets of SR for HCC treatment. e network between the components and corresponding targets was constructed and visualized using the Cytoscape software 3.7.2
Summary
Hepatocellular carcinoma (HCC) is the fifth most common and lethal malignancy in the world [1]. It is a complex disease closely linked to chronic viral infection, carcinogenesis of toxins, and cirrhosis induced by fatty liver disease or alcohol abuse and genetic factors [2]. Several common therapeutic options for HCC are currently considered, including surgical resection, local ablation, transarterial chemoembolization, liver transplantation, and systemic treatment with sorafenib [3]. A majority of patients with HCC are diagnosed at advanced stages, and the only feasible treatment for these patients is sorafenib [4]. Erefore, more effective alternative therapies with low toxicity should be developed to improve the overall survival of patients with HCC Less than 20% of patients respond well to sorafenib that often causes serious adverse reactions [5]. erefore, more effective alternative therapies with low toxicity should be developed to improve the overall survival of patients with HCC
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