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Review
. 2016 Jul 12:7:201.
doi: 10.3389/fphar.2016.00201. eCollection 2016.

Synergistic Effects of Chinese Herbal Medicine: A Comprehensive Review of Methodology and Current Research

Xian Zhou  1 , Sai Wang Seto  1 , Dennis Chang  1 , Hosen Kiat  2 , Valentina Razmovski-Naumovski  3 , Kelvin Chan  4 , Alan Bensoussan  1
Affiliations
Review

Synergistic Effects of Chinese Herbal Medicine: A Comprehensive Review of Methodology and Current Research

Xian Zhou et al. Front Pharmacol. .

Abstract

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. 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. 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. 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. We discuss the strengths and weaknesses of these models in the context of CHM and summarize the current status of synergy research in CHM. 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. There remain significant challenges in the development of suitable methods for synergistic studies of complex herbal combinations.

Keywords: Chinese herbal medicine; combination index; interaction; isobologram; synergy; system biology.

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Figures

Figure 1
Figure 1
An example of utilizing CI model to determine synergy for the combination of agent AB in certain fixed ratio. (A) Dose-effect curves for A, B, and AB, respectively. (B) CI value-Fa (Fa: fraction affected level) curve for AB generated from CalcuSyn based on the dose-response curves shown in (A). It demonstrated that synergistic effect is starting from 60% effective level (Fa = 0.6) and this synergistic effect continues to increase (CI < 1) at higher effect levels in AB.
Figure 2
Figure 2
The lsobole method for synergy study. Dose A and Dose B are the individual concentrations of Components A and B; Dose AB are the concentrations of A and B in the combination. The dashed line shows zero interaction between A and B, which represents a simple additive effect. The effect of the combination equals the sum of the effects from individual components. (A) Effect of synergy: the dot is underneath the dashed line. (B) Effect of antagonism: The dot is above the dashed line; Addition: The dot is on the dashed line.
Figure 3
Figure 3
Histogram showing the general increase in synergy of Chinese herbal medicine related publications in the years 1999–2015 (up to June only for 2015) from a bibliographic search in PubMed and Google Scholar database carried out in June 2015.
See this image and copyright information in PMC

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