Abstract:
:Over the past several decades, natural products with poly-pharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Berberine (PubChem CID: 2353), a soliloquies quaternary alkaloid, has been validated to exert powerful effects in many cancers. However, the underlying molecular mechanism is not yet fully elucidated. In this study, we summarized the molecular effects of berberine against multiple cancers based on current available literatures. Furthermore, a systems pharmacology infrastructure was developed to discover new cancer indications of berberine and explore their molecular mechanisms. Specifically, we incorporated 289 high-quality protein targets of berberine by integrating experimental drug-target interactions (DTIs) extracted from literatures and computationally predicted DTIs inferred by network-based inference approach. Statistical network models were developed for identification of new cancer indications of berberine through integration of DTIs and curated cancer significantly mutated genes (SMGs). High accuracy was yielded for our statistical models. We further discussed three typical cancer indications (hepatocarcinoma, lung adenocarcinoma, and bladder carcinoma) of berberine with new mechanisms of actions (MOAs) based on our systems pharmacology framework. In summary, this study systematically provides a powerful strategy to identify potential anti-cancer effects of berberine with novel mechanisms from a systems pharmacology perspective.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Guo P,Cai C,Wu X,Fan X,Huang W,Zhou J,Wu Q,Huang Y,Zhao W,Zhang F,Wang Q,Zhang Y,Fang Jdoi
10.3389/fphar.2019.00857subject
Has Abstractpub_date
2019-08-06 00:00:00pages
857issn
1663-9812journal_volume
10pub_type
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