Herranz-López María, Losada-Echeberría María, Barrajón-Catalán Enrique
Instituto de Biología Molecular y Celular (IBMC) and Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández 03202 Elche, Spain.
Medicines (Basel). 2018 Dec 28;6(1):6. doi: 10.3390/medicines6010006.
It is estimated that over 60% of the approved drugs and new drug developments for cancer and infectious diseases are from natural origin. The use of natural compounds as a potential source of antitumor agents has been deeply studied in many cancer models, both in vitro and in vivo. Most of the Western medicine studies are based on the use of highly selective pure compounds with strong specificity for their targets such as colchicine or taxol. Nevertheless, approximately 60% of fairly specific drugs in their initial research fail because of toxicity or ineffectiveness in late-stage preclinical studies. Moreover, cancer is a multifaceted disease that in most cases deserves a polypharmacological therapeutic approach. Complex plant-derived mixtures such as natural extracts are difficult to characterize and hardly exhibit high pharmacological potency. However, in some cases, these may provide an advantage due to their multitargeted mode of action and potential synergistic behavior. The polypharmacology approach appears to be a plausible explanation for the multigargeted mechanism of complex natural extracts on different proteins within the same signalling pathway and in several biochemical pathways at once. This review focuses on the different aspects of natural extracts in the context of anticancer activity drug development, with special attention to synergy studies and xenohormesis.
据估计，超过60%的已批准用于癌症和传染病的药物以及新药研发都源自天然物质。在许多癌症模型中，无论是体外还是体内，天然化合物作为潜在抗肿瘤药物来源的应用都得到了深入研究。大多数西医研究基于使用对其靶点具有高度选择性的纯化合物，如秋水仙碱或紫杉醇。然而，大约60%在初步研究中相当有针对性的药物在临床前后期研究中因毒性或无效而失败。此外，癌症是一种多方面的疾病，在大多数情况下需要采用多药联合治疗方法。复杂的植物提取物等混合物难以表征，且几乎不具有高药理活性。然而，在某些情况下，由于它们的多靶点作用模式和潜在的协同行为，这些混合物可能具有优势。多药联合治疗方法似乎是复杂天然提取物对同一信号通路内不同蛋白质以及同时在多个生化途径中产生多靶点作用机制的合理解释。本综述重点关注天然提取物在抗癌活性药物研发背景下的不同方面，特别关注协同研究和异种应激效应。
