Wagner Hildebert, Efferth Thomas
Department Pharmacy, Center for Pharma Research, Butenandtstr. 5, House B, 81377 Munich, Germany.
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Phytomedicine. 2017 Dec 15;37:1-3. doi: 10.1016/j.phymed.2017.10.020. Epub 2017 Nov 2.
There is a paradigm shift in chemotherapy from mono-drug therapy towards multidrug combination regimens. Natural products from medicinal plants may play an important role for the design of novel combination therapy protocols.
We introduce the novel term "hybrid combination" for the therapeutic combination of chemically defined plant-derived constituents (e.g. phenolic or terpenoid compounds with synthetic or antibiotic drugs to increase pharmacological activity and simultaneously toxic side effects.
Several literature databases were screened on the combination of phenolic/terpenoid compounds with synthetic/antibiotic drugs.
Phenolic compounds are water soluble and interact with target proteins due to their OH-groups. They reveal antioxident, antiinflammatory and sometimes apoptotic activities whereas the terpenoids possess due to their lipophilic nature together with the phenolics amphiphilic properties and thereby good cell-penetrating features They reveal antioxidant properties, anti-inflammatory and sometimes apoptotic activities as well as cell-penetrating features due to their amphiphilicity. Synergistic or antagonistic interactions with synthetic or antibiotic drugs have to be demonstrated by using suitable methods (e.g. isobologram analysis). The molecular modes of action may be elucidated by approaches of network pharmacology (e.g. protein-protein interaction networks).
There is convincing evidence for the improvement of pharmacological activity at reduced side effects by hybrid combinations. Future efforts should focus on clinical trials with hybrid combinations to treat a broad range of diverse diseases such as cardiometabolic and neurotropic syndromes, drug resistance phenotypes, and so-called neglected infectious diseases.
化疗正从单一药物治疗向多药联合方案发生范式转变。药用植物中的天然产物可能在新型联合治疗方案的设计中发挥重要作用。
我们引入了“混合组合”这一新术语，用于化学定义的植物衍生成分（如酚类或萜类化合物）与合成药物或抗生素的治疗组合，以提高药理活性并同时降低毒副作用。
对几个文献数据库进行了筛选，以查找酚类/萜类化合物与合成药物/抗生素的组合情况。
酚类化合物具有水溶性，因其羟基可与靶蛋白相互作用。它们具有抗氧化、抗炎作用，有时还具有凋亡活性，而萜类化合物由于其亲脂性，与酚类化合物一起具有两亲性，从而具有良好的细胞穿透特性。由于具有两亲性，它们还具有抗氧化特性、抗炎作用，有时具有凋亡活性以及细胞穿透特性。与合成药物或抗生素的协同或拮抗相互作用必须通过合适的方法（如等效线图分析）来证明。作用的分子模式可以通过网络药理学方法（如蛋白质 - 蛋白质相互作用网络）来阐明。
有令人信服的证据表明，混合组合可在降低副作用的情况下提高药理活性。未来的工作应集中于混合组合治疗多种不同疾病的临床试验，如心脏代谢和神经otropic综合征、耐药表型以及所谓的被忽视的传染病。 （注：原文中“neurotropic”疑似拼写错误，可能是“neurotrophic”，但按照要求未做修改）
