Impact Factor


Original Research ARTICLE

Front. Neurosci., 20 February 2013 | http://dx.doi.org/10.3389/fnins.2013.00016

Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells

  • 1Swedish Herbal Institute Research and Development, Göteborg, Sweden
  • 2Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany

Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents – extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor signaling pathways, i.e., cAMP, phospholipase C (PLC), and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by down-regulation of adenylate cyclase gene ADC2Y and up-regulation of phosphodiesterase gene PDE4D that is essential for energy homeostasis as well as for switching from catabolic to anabolic states and vice versa. Down-regulation of cAMP by adaptogens may decrease cAMP-dependent protein kinase A activity in various cells resulting in inhibition stress-induced catabolic transformations and saving of ATP for many ATP-dependant metabolic transformations. All tested adaptogens up-regulated the PLCB1 gene, which encodes phosphoinositide-specific PLC and phosphatidylinositol 3-kinases (PI3Ks), key players for the regulation of NF-κB-mediated defense responses. Other common targets of adaptogens included genes encoding ERα estrogen receptor (2.9–22.6 fold down-regulation), cholesterol ester transfer protein (5.1–10.6 fold down-regulation), heat shock protein Hsp70 (3.0–45.0 fold up-regulation), serpin peptidase inhibitor (neuroserpin), and 5-HT3 receptor of serotonin (2.2–6.6 fold down-regulation). These findings can be reconciled with the observed beneficial effects of adaptogens in behavioral, mental, and aging-associated disorders. Combining two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic interactions result in suppression some genes activated by individual substances. These interactions can have an influence on transcriptional control of metabolic regulation both on the cellular level and the level of the whole organism. Merging of deregulated genes array profiles and intracellular networks is specific to the new substance with unique pharmacological characteristics. Presumably, this phenomenon could be used to eliminate undesirable effects (e.g., toxic effects) and increase the selectivity of pharmacological intervention.

Keywords: pharmacogenomics, Rhodiola rosea, Schisandra chinensis, Eleutherococcus senticosus, ADAPT-232, salidroside, eleutheroside E, schizandrin B

Citation: Panossian A, Hamm R, Kadioglu O, Wikman G and Efferth T (2013) Synergy and antagonism of active constituents of ADAPT-232 on transcriptional level of metabolic regulation of isolated neuroglial cells. Front. Neurosci. 7:16. doi: 10.3389/fnins.2013.00016

Received: 19 November 2012; Accepted: 01 February 2013;
Published online: 20 February 2013.

Edited by:

María M. Malagón, University of Cordoba, Spain

Reviewed by:

Jae Young Seong, Korea University, South Korea
JulieAnn Chowen, Hospital Infantil Universitario Niño Jesús, Spain

Copyright: © 2013 Panossian, Hamm, Kadioglu, Wikman and Efferth. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Alexander Panossian, Swedish Herbal Institute Research and Development, Gröndalsgatan 11 A, SE-412 62 Göteborg, Sweden. e-mail: alexander.panossian@shi.se