Adaptogens in chemobrain (Part I): Plant extracts attenuate cancer chemotherapy-induced cognitive impairment - Transcriptome-wide microarray profiles of neuroglia cells.

Background:Cancer chemotherapy-induced cognitive impairmentsarepresumably associated with undesirableeffects of chemotherapy on physiological functions of brain cells. Adaptogens are naturalcompounds or plant extracts increasingan organism’s adaptability and survival in stress.They exhibitedneuroprotective effectsand increasedcognitive functions in clinical studies in humanbeings. Hypothesis:We hypothesized thatselected adaptogenic plant extracts attenuate or prevent cancer chemotherapy-induced cognitive impairments. Aim:Weassessedthe effects of selected adaptogenic herbal extracts on FEC (fixed combination 5-fluorouracil, epirubicin and cyclophosphamide) induced changes in transcriptome-wide RNA microarrayprofiles of neuroglia cells. The aimof the study was to predict potentialeffects of andrographolide, Andrographisherb, Eleutherococcusrootgenuine extracts,their fixed combination(AE) and the combination of Rhodiolaroots,SchisandraberriesandEleutherococcusroots(RSE)on cellular and physiological, mostly cognitivefunctions. Methods:Gene expression profiling was performedbytranscriptome-wide mRNA microarrayin the human T98G neurogliacells after treatment withadaptogens. Interactive pathways downstream analysis was performed with data sets of significantly up-or down-regulated genes and predicted effects on cellular functions and diseases were identified by Ingenuity IPA database software. Results:FEC deregulated67 genes involved in decrease of neuronal development, 37 genes involved in development of the sensory system, 12 genes in extension of axons,and 3 genes in migration of neurons. Co-incubation with Andrographis paniculata(AP)suppressedFEC-induced deregulation of a large number of genes involved in predicted activation ofneuronal death and inhibition ofneurogenesis,and 16 genes related to inhibition of several functions in the nervous system. Co-incubation with AEsuppressedFEC-induced deregulation ofanumber of genes involved in predicted inhibition of axonextension, migration ofT98G neuroglia cells, conduction of nerves and other genes related to regulationsofsome other functions in thenervous system. Conclusion:Application of cytostatic drugs in combination with apoptogenic plant extractsinducedsignificant changes in transcriptome-wide mRNA microarrayprofilesof neuroglial cells. These changes indicate on potential beneficialeffectson neuronal functions associated with mild cognitive impairments in cancer chemotherapy.