Synergy and antagonism of active constituents in a complex herbal formulation on metabolic regulation at a transcriptional level

Gene expression profiling was conducted on the human neuroglial cell line, T98G, after treatment with either a complex herbal formulation (ADAPT-232) or its constituents, which included extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root or several individual constituents, including eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. The concentration at which the compounds were tested strongly influenced both the intensity of the cellular response and the profile of differentially expressed genes. Combining two or more active substances in one mixture significantly changed deregulated gene profiles: synergetic interactions resulted in activation of genes that none of the individual substances affected; antagonistic interactions resulted in suppression of some genes that had been activated by the individual substances. These interactions may influence transcriptional control of metabolic regulation, on both the cellular and the whole organism levels. This study was the first to demonstrate that combining active substances with different deregulated gene array profiles and intracellular networks could produce a new substance with unique pharmacological characteristics. Thus, the mixture of two chemical substances could produce a qualitatively new substance, biologically different from its constituents. Presumably, this phenomenon could be used to eliminate undesirable effects (e.g. toxic effects) and increase the selectivity of pharmacological interventions.