This paradigm shift has been partly driven by its limited effectiveness in chronic diseases, treatment resistance, and side effects of synthetic mono-drugs. However, over the last decade, this mono-substance therapy model has gradually shifted toward the adoption of combination therapies, in which multiple active components are employed. The “one drug, one target, one disease” approach has for some time remained the conventional pharmaceutical approach to the development of medicines and treatment strategies. There remain significant challenges in the development of suitable methods for synergistic studies of complex herbal combinations. Despite the availability of some scientific data to support the synergistic effects of multi-herbal and/or herb-drug combinations, the level of evidence remains low, and the clinical relevancy of most of these findings is undetermined. We discuss the strengths and weaknesses of these models in the context of CHM and summarize the current status of synergy research in CHM. In this review, we clarify the definition of synergy, identify common errors in synergy research and describe current methodological approaches to test for synergistic interaction. However, evidence to support these synergistic effects remains weak and controversial due to several reasons, including the very complex nature of CHM, misconceptions about synergy and methodological challenges to study design. There seems to be a general assumption that the synergistic therapeutic effects of Chinese herbal medicine (CHM) derive from the complex interactions between the multiple bioactive components within the herbs and/or herbal formulations. Traditional Chinese medicine (TCM) is an important part of primary health care in Asian countries that has utilized complex herbal formulations (consisting 2 or more medicinal herbs) for treating diseases over thousands of years. 6Faculty of Science, TCM Division, University of Technology, Sydney, NSW, Australia.
5School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpoor, UK.4Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.3School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.2Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.1School of Science and Health, National Institute of Complementary Medicine, Western Sydney University, Penrith, NSW, Australia.Xian Zhou 1 *, Sai Wang Seto 1, Dennis Chang 1, Hosen Kiat 2,3,4, Valentina Razmovski-Naumovski 1,2, Kelvin Chan 1,5,6 and Alan Bensoussan 1
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