Liver cancer is the fourth leading cause of cancer death worldwide, and hepatocellular carcinoma (HCC) accounts for the greatest proportion of these deaths. Baicalein, a flavonoid isolated from the root of Scutellariae radix, is considered a potential candidate to treat HCC. However, the underlying molecular mechanisms remain poorly understood. In the present study, a network pharmacological approach was combined with microarray data (GSE95504) acquired from the Gene Expression Omnibus database to reveal the therapeutic mechanisms of action of baicalein at a systemic level. We identified 38 baicalein targets and 76 differently expressed genes (DEGs) following treatment with baicalein, including 55 upregulated and 21 downregulated genes. The DEGs were significantly enriched in the biological functions of apoptosis, endoplasmic reticulum stress, and PERK-mediated unfolded protein response. Protein-protein interaction (PPI) network construction and topological screening revealed a core module of PPIs including two baicalein targets, TP53 and CDK1, and two downregulated DEGs, HSPA1A and HSPA1B. Expression and survival data for these genes in the module derived from Gene Expression Profiling Interactive Analysis (GEPIA) were subjected to Kaplan–Meier analysis of overall survival and disease-free survival. Overexpression of CDK1, BRCA1, TUBB, HSPA1A, HSPA1B, and HSPA4 was associated with significantly worse overall survival, while overexpression of CDK1, CLU7, BRCA1, and TUBB was associated with significantly worse disease-free survival. These data suggest that baicalein exerts therapeutic effects against HCC via a PPI network involving TP53, CDK1, HSPA1A, and HSPA1B.

Ischemic stroke is accompanied by high mortality and morbidity rates. At present, there is no effective clinical treatment. Alternatively, traditional Chinese medicine has been widely used in China and Japan for the treatment of ischemic stroke. Baicalin is a flavonoid extracted from Scutellaria baicalensis that has been shown to be effective against ischemic stroke; however, its mechanism has not been fully elucidated. Based on network pharmacology, we explored the potential mechanism of baicalin on a system level. After obtaining baicalin structural information from the PubChem database, an approach combined with literature mining and PharmMapper prediction was used to uncover baicalin targets. Ischemic stroke‐related targets were gathered with the help of DrugBank, Online Mendelian Inheritance in Man (OMIM), Genetic Association Database (GAD), and Therapeutic Target Database (TTD). Protein‐protein interaction (PPI) networks were constructed through the Cytoscape plugin BisoGenet and analyzed by topological methods. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. We obtained a total of 386 potential targets and 5 signaling pathways, including mitogen‐activated protein kinase (MAPK), phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT), hypoxia‐inducible factor‐1 (HIF‐1), nuclear factor kappa B (NF‐κB), and forkhead box (FOXO) signaling pathways. GO analysis showed that these targets were associated with antiapoptosis, antioxidative stress, anti‐inflammation, and other physiopathological processes that are involved in anti‐ischemic stroke effects. In summary, the mechanism of baicalin against ischemic stroke involved multiple targets and signaling pathways. Our study provides a network pharmacology framework for future research on traditional Chinese medicine.

Traditional Chinese medicine (TCM) has a longstanding history and has gained widespread clinical applications. San Cao Decoction (SCD) is an experience prescription first formulated by Prof. Duzhou Liu. We previously demonstrated its antihypertensive effects; however, to systematically explain the underlying mechanisms of action, we employed a systems pharmacology approach for pharmacokinetic screening and target prediction by constructing protein-protein interaction networks of hypertension-related and putative SCD-related targets, and Database for Annotation, Visualization, and Integrated Discovery enrichment analysis. We identified 123 active compounds in SCD and 116 hypertension-related targets. Furthermore, the enrichment analysis of the drug-target network showed that SCD acts in a multidimensional manner to regulate PI3K-Akt-endothelial nitric oxide synthase signaling to maintain blood pressure. Our results highlighted the molecular mechanisms of antihypertensive actions of medicinal herbs at a systematic level.

[This corrects the article DOI: 10.1155/2018/2582843.].