Synergy and antagonism

In 1957, Goldin and Mantel suggested that “Synergy and antagonism imply that the different constituents affect each other’s actions” assuming that “if
it is synergistic, the drugs will be more effective in combination than separately” (Goldin and Mantel, 1957). Thus, one of two commonly used definitions of synergy in pharmacology and pharmacognosy is related to efficacy, effectiveness, and potency of the combinations of two agents with the same pharmacological activity: “A combination of agents that ismore effective than is expected from the effectiveness of its constituents is said to show synergy” (Berenbaum, 1977).
Another definition of synergy is formulated as “two or more agents working together to produce a result not obtainable by any of the agents independently”
and can be interpreted as generation of new pharmacological activity, which is specific only for the combination of two or more agents (Panossian et al., 2018; Panossian at al. 2015; Panossian et al., 2013; Skirven et.al., 2011).

In this context, it would be reasonable to distinguish among definitions of synergy and implement more relevant definitions for assessing efficacy or effectiveness of the combination (hybrid substance C) of efficacy substances A and B, such as:

•synergy, if efficacy of C is>0 while efficacies of A=0 and B=0, 0+0>0;

•amplification, if 1+1>2, instead of synergy;

•potentiation, if 0+1>1;

•antagonism, if efficacy of C is 0 while efficacies of A=1 and B=1, 1+1=0;

•attenuation, if 1+1<2;

•addition, if 1+1=2 (Panossian et al., 2018)

The term synergy is more suitable for interactions of two or more agents resulting in qualitatively new pharmacological effect, e.g., gene expression that cannot be obtained by any single constituent independently (Panossian et al., 2013; 2015; 2018;2019; Seo et al., 2018;2019). Similarly, antagonism results from interactions of several constituents in combination, leading to a lack, reduction, or prevention of effects that any individual ingredient inthat combination yields (Panossian et al., 2018; Panossian et al., 2013). These definitions are suitable and relevant to pharmacological studies of combinations of plant extracts, where the main focus is the discovery of unexpected potential indications and toxic effects of the combinations from complex intracellular and extracellular interactions of molecular networks with many players at several phases of development of final pharmacological outcomes (Panossian et al., 2018)

References

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