Computational Biology and Chemistry 35 (2011) 293–297 Contents lists available at ScienceDirect Computational Biology and Chemistry jo ur n al homep age: www.elsevier.com/locate/compbiolchem Brief communication Drug–target network and polypharmacology studies of a Traditional Chinese Medicine for type II diabetes mellitus Jiangyong Gu a , Hu Zhang a,b , Lirong Chen a , Shun Xu b , Gu Yuan a , Xiaojie Xu a,∗ a Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, PR China b Department of Chemistry, Zhengzhou University, Zhengzhou 450052, PR China a r t i c l e i n f o Article history: Received 4 November 2010 Received in revised form 18 June 2011 Accepted 3 July 2011 Keywords: Type II diabetes Network analysis Virtual screening Traditional Chinese Medicine Drug–target network Polypharmacology a b s t r a c t Many Traditional Chinese Medicines (TCMs) are effective to relieve complicated diseases such as type II diabetes mellitus (T2DM). In this work, molecular docking and network analysis were employed to elucidate the action mechanism of a medical composition which had clinical efficacy for T2DM. We found that multiple active compounds contained in this medical composition would target multiple proteins related to T2DM and the biological network would be shifted. We predicted the key players in the medical composition and some of them have been reported in literature. Meanwhile, several compounds such as Rheidin A, Rheidin C, Sennoside C, procyanidin C1 and Dihydrobaicalin were notable although no one have reported their pharmacological activity against T2DM. The association between active compounds, target proteins and other diseases was also discussed. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Diabetes mellitus has become a serious health problem since it has affected more than 285 million people according to the statistical data of the International Diabetes Federation (http://www.diabetesatlas.org) and more than 90% of these dia- betic patients have type II diabetes mellitus which is mostly caused by insulin resistance. However, T2DM concerns with hereditary fac- tors, insulin resistance (related to free fatty acids, inflammatory cytokines, adipokines, etc.) and -cell dysfunction (Stumvoll et al., 2005). Even more important, T2DM would share some target pro- teins with cardiovascular diseases underlying biological pathways and processes (DeSouza and Fonseca, 2009), a positive correlation between the risks of T2DM and CVD does exits (Mellbin et al., 2010). Although there are many drugs for T2DM, none of them can cure it (Morral, 2003; Stumvoll et al., 2005). T2DM is so complicated that magic bullets which selectively target at one protein could not pull the whole biological network (interactions between proteins, nucleic acid and small molecules) back to healthy state (Berger and Iyengar, 2009; Janga and Tzakos, 2009). However, network-based approach is becoming more and more powerful to deal with com- plex systems (Barabasi, 2009; Girvan and Newman, 2002; Janga and Tzakos, 2009; Kitano, 2004; Luni et al., 2010). Recently, Janga and ∗ Corresponding author. Tel.: +86 10 62757456. E-mail address: xiaojxu@pku.edu.cn (X. Xu). Contreras-Moreira (2010) elucidated the power of network-based approaches in identifying disease markers and drug discovery. Typically, the drug–target network which links drugs and protein targets was used to interpret the mechanism of drug action (Zhu et al., 2009) and explore polypharmacology (Berger and Iyengar, 2009; Gu et al., 2009; Janga and Tzakos, 2009; Vogt and Mestres, 2010; Yildirim et al., 2007) and predict new targets for drugs (Klipp et al., 2010); the protein–disease network was employed to discover the association between diseases and target proteins (Barabasi and Oltvai, 2004; Goh et al., 2007; Janga and Contreras- Moreira, 2010; Klipp et al., 2010; Vogt and Mestres, 2010; Yildirim et al., 2007). Some Traditional Chinese Medicines which contain many active compounds might target at multiple proteins in the biological net- work and then the biological system would attain new equilibrium in order to reduce the harmful impact (Gu et al., 2009; Janga and Tzakos, 2009). Recently, Tasly Pharmaceutical Corporation (Tian- jin, China) developed a medical composition (Tangminling Pills) which was very effective for relieving T2DM (Tong et al., 2009). This medical composition comprises eleven Chinese herb medicines: Trichosanthes kirilowii, Bupleurum longiradiatum, Citrus sinensis, Rheum officinale, Pinellia ternata, Scutellaria baicalensis, Coptis chi- nensis, Paeonia sterniana, Prunus mume, Astragalus membranaceus and Crataegus pinnatifida. 676 molecules contained in the medical composition were retrieved and docked to 37 T2DM-related pro- teins and then network analysis was conducted to elucidate the action mechanism. We found that more than one hundred active 1476-9271/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.compbiolchem.2011.07.003