鄂西香茶菜甲素作为抗肿瘤先导物的发现与抗肿瘤活性验证  

Discovery and activity verification of reniformin A as an anti-tumor leading compound

作　　者：龚曼[1,2] 杨联河 朱利利[1,2] 冯庆梅 许二平 代丽萍[1,2,3] 王智民 GONG Man;YANG Lian-he;ZHU Li-li;FENG Qing-mei;XU Er-ping;DAI Li-ping;WANG Zhi-min(Henan University of Chinese Medicine,Zhengzhou 450046,China;Engineering Technology Research Center for Comprehensive Development and Utilization of Authentic Medicinal Materials from Henan,Zhengzhou 450046,China;Henan Zhongjing Key Laboratory of Prescription,Zhengzhou 450046,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]河南中医药大学,河南郑州450046 [2]河南省道地药材综合开发与利用工程中心,河南郑州450046 [3]河南省仲景方药重点实验室,河南郑州450046 [4]中国中医科学院中药研究所,北京100700

出　　处：《中国中药杂志》2021年第16期4061-4068,共8页China Journal of Chinese Materia Medica

基　　金：中央本级重大增减支项目(2060302);河南省中央引导地方科技发展专项(YDZX20204100004985)。

摘　　要：采用反向预测和分子对接技术,评价鄂西香茶菜甲素成为抗肿瘤先导物的可行性。在反向预测的基础上,利用网络药理学技术构建"疾病-化合物-靶点-通路"网络。结果显示,鄂西香茶菜甲素预测靶点中有39个与肿瘤密切相关,参与调节细胞凋亡、细胞周期、肿瘤转移等多种细胞活动,并可调节雌激素信号转导途径和炎症应答。采用Discovery Studio 2020软件进行分子对接及TOPKAT毒性预测;鄂西香茶菜甲素与肿瘤相关靶点ABL1、ESR1、SRC、BCL-XL的结合亲和力均强于冬凌草甲素,且其致突变性、啮齿动物致癌性、大鼠口服LD50毒性均小于冬凌草甲素;进而,采用体外实验证实了鄂西香茶菜甲素的抗肿瘤活性,并初步探讨了其作用机制。结果显示,鄂西香茶菜甲素在细胞毒、抑制细胞集落形成和诱导凋亡方面均优于冬凌草甲素。鄂西香茶菜甲素有望成为新的抗肿瘤先导物,具有较大的研究前景。且鄂西香茶菜素对雌激素信号转导通路调节作用的预测结果值得进行深入研究,为其抗肿瘤作用机制的研究提供新视角。Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD50 in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.

关 键 词：反向预测 分子对接 毒性预测 鄂西香茶菜甲素 先导物 

分 类 号：R285[医药卫生—中药学]