Introduction: Novel hybrid combinations containing synthetic or antibiotic drugs with plant-derived phenolic or terpenoid compounds.

BACKGROUND: 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.

HYPOTHESIS: 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.

STUDY DESIGN: Several literature databases were screened on the combination of phenolic/terpenoid compounds with synthetic/antibiotic drugs.

RESULTS: 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).

CONCLUSION: 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.