TY - JOUR AU - Guo, Pengfei AU - Cai, Chuipu AU - Wu, Xiaoqin AU - Fan, Xiude AU - Huang, Wei AU - Zhou, Jingwei AU - Wu, Qihui AU - Huang, Yujie AU - Zhao, Wei AU - Zhang, Fengxue AU - Wang, Qi AU - Zhang, Yongbin AU - Fang, Jiansong PY - 2019 M3 - Original Research TI - An Insight Into the Molecular Mechanism of Berberine Towards Multiple Cancer Types Through Systems Pharmacology JO - Frontiers in Pharmacology UR - https://www.frontiersin.org/articles/10.3389/fphar.2019.00857 VL - 10 SN - 1663-9812 N2 - 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. ER -