Zheng Chun-Song, Wu Yin-Sheng, Bao Hong-Juan, Xu Xiao-Jie, Chen Xing-Qiang, Ye Hong-Zhi, Wu Guang-Wen, Xu Hui-Feng, Li Xi-Hai, Chen Jia-Shou, Liu Xian-Xiang
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Department of Pharmacy, Xiamen Medical College, Xiamen, Fujian 361008, P.R. China.
Exp Ther Med. 2014 Jun;7(6):1777-1783. doi: 10.3892/etm.2014.1660. Epub 2014 Apr 2.
Xiao Chai Hu Tang (XCHT), a traditional herbal formula, is widely administered as a cancer treatment. However, the underlying molecular mechanisms of its anticancer effects are not fully understood. In the present study, a computational pharmacological model that combined chemical space mapping, molecular docking and network analysis was employed to predict which chemical compounds in XCHT are potential inhibitors of cancer-associated targets, and to establish a compound-target (C-T) network and compound-compound (C-C) association network. The identified compounds from XCHT demonstrated diversity in chemical space. Furthermore, they occupied regions of chemical space that were the same, or close to, those occupied by drug or drug-like compounds that are associated with cancer, according to the Therapeutic Targets Database. The analysis of the molecular docking and the C-T network demonstrated that the potential inhibitors possessed the properties of promiscuous drugs and combination therapies. The C-C network was classified into four clusters and the different clusters contained various multi-compound combinations that acted on different targets. The study indicated that XCHT has a polypharmacological role in treating cancer and the potential inhibitory components of XCHT require further investigation as potential therapeutic strategies for cancer patients.
小柴胡汤(XCHT)是一种传统草药配方,被广泛用作癌症治疗药物。然而,其抗癌作用的潜在分子机制尚未完全明确。在本研究中,采用了一种结合化学空间映射、分子对接和网络分析的计算药理学模型,以预测小柴胡汤中的哪些化合物是癌症相关靶点的潜在抑制剂,并建立化合物-靶点(C-T)网络和化合物-化合物(C-C)关联网络。从小柴胡汤中鉴定出的化合物在化学空间上表现出多样性。此外,根据治疗靶点数据库,它们占据的化学空间区域与与癌症相关的药物或类药物化合物所占据的区域相同或接近。分子对接和C-T网络分析表明,潜在抑制剂具有多靶点药物和联合治疗的特性。C-C网络被分为四个簇,不同的簇包含作用于不同靶点的各种多化合物组合。该研究表明,小柴胡汤在治疗癌症方面具有多药理学作用,小柴胡汤的潜在抑制成分作为癌症患者的潜在治疗策略需要进一步研究。