Abstract
Network pharmacology is considered as the next paradigm in drug discovery. In an era when obesity has become global epidemic, network pharmacology becomes an ideal tool to discover novel herbal-based therapeutics with effective anti-obesity effects. Zanthoxylum bungeanum Maxim (ZBM) is a medicinal herb. The mature pericarp of ZBM is used for disease treatments and as spice for cooking. Here, we used the network pharmacology approach to investigate whether ZBM possesses anti-obesity effects and reveal the underlying mechanism of action. We first built up drug–ingredient–gene symbol–disease network and protein–protein interaction network of the ZBM-related obesity targets, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The results highlight apoptosis as a promising signaling pathway that mediates the anti-obesity effects of ZBM. Molecular docking also reveals quercetin, a compound in ZBM has the highest degree of connections in the compound-target network and has direct bindings with the apoptotic markers. Furthermore, the apoptotic effects of ZBM are further validated in 3T3-L1 adipocytes and in the high-fat diet–induced obesity mouse model. These findings not only suggest ZBM can be developed as potential anti-obesity therapeutics but also demonstrate the application of network pharmacology for the discovery of herbal-based therapeutics for disease treatments.
Highlights
We investigated the potential mechanisms of action underlying the anti-obesity effects of Zanthoxylum bungeanum Maxim (ZBM)
Our analysis suggests that the interactions between these apoptotic markers and quercetin underline the apoptotic effects of ZBM
We have established the PPI network that highlights a total of 35 proteins that may represent the critical molecular targets that mediate the anti-obesity effects of ZBM
Summary
Based on the data reported by the Centers for Disease Control and Prevention, the prevalence of obesity in the United States has increased from 30.5 to 42.4%, and the prevalence of severe obesity has increased from 4.7 to 9.2% in the last decade (Agha and Agha, 2017). Asian countries such as China have 46% of adults being obese or overweight (Wang et al, 2019b). Obesity is associated with many comorbid conditions and is the main risk factor for many noncommunicable diseases. Obesity and its associated conditions cast a heavy burden on the health sector
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