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Alexander Panossian - One of the best experts on this subject based on the ideXlab platform.

  • Adaptogens in chemobrain part ii effect of plant extracts on chemotherapy induced cytotoxicity in neuroglia cells
    Phytomedicine, 2019
    Co-Authors: Eanjeong Seo, Thomas Efferth, Sabine M Klauck, Alexander Panossian
    Abstract:

    Abstract Background Cancer chemotherapy-induced cognitive impairments are apparently associated with harmful effects on physiological functions of brain cells. Adaptogens, are known to exhibit neuroprotective effects and to increase cognitive functions in clinical studies. In our previous study (Seo et al., 2018), we demonstrated that selected Adaptogenic extracts significantly attenuate cytostatic-induced regulation of more than 100 genes involved in the activation of neuronal death and inhibiting neurogenesis. Neuroprotective and cytoprotective activities of Adaptogens rise the question about their possible impact on cytostatic effects of a chemotherapeutic combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC). Aim The aim of this study was to assess the effects of selected Adaptogenic herbal extracts, namely of andrographolide (AND), Herba Andrographidis (AP), Radix Eleutherococci (ES) genuine extracts, their fixed combination (AE), and the combination of three Adaptogenic herbs, Rhodiola Radix, Shisandra Fructus and Eleutherococci Radix (RSE) on the cytotoxicity of a fixed combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) on neuroglia cells. Methods Cytotoxicity of FEC, Adaptogenic extracts and their combination with FEC was tested on isolated T98G cells in a wide range of concentrations of all tested compounds. Results FEC reproducibly inhibited the proliferation of T98G cells by 50% at concentrations of 5 × 10−1 µg/ml epirubicin, 500 × 10−1 µg/ml 5-fluorouracil and 20 × 10−1 µg/ml 4-hydroperoxycyclophosphamide after 24 h incubation of cells. These concentrations were subsequently used for experiments with Adaptogenic extracts. The cytotoxic activity of FEC was not significantly changed in the presence of AND, ES and AE. Furthermore, it was potentiated by AP extract and RSE in concentrations of 0.06–6 µg/ml and 17.6–26.4 µg/ml. Conclusion The neuroprotective effect of Adaptogens did not attenuate the cytotoxic activity of FEC. Application of cytostatic drugs in combination with Adaptogenic plant extracts likely have no impact in cytotoxic effect of FEC. Furthermore, AP and RSE potentiated the cytotoxic effects of FEC.

  • Adaptogens in chemobrain part iii antitoxic effects of plant extracts towards cancer chemotherapy induced toxicity transcriptome wide microarray analysis of neuroglia cells
    Phytomedicine, 2019
    Co-Authors: Eanjeong Seo, Thomas Efferth, Sabine M Klauck, Alexander Panossian
    Abstract:

    Abstract Background Toxicity of chemotherapeutics is a serious problem in cancer therapy. Adaptogens are known to increase adaptability and survival organisms. Aim The aim of this study was to assess the effects of selected Adaptogenic herbal extracts on FEC (fixed combination of 5-fluorouracil, epirubicin and cyclophosphamide) induced changes in transcriptome-wide microarray profiles of neuroglia cells. Another task of the study was to identify those genes, which are associated with FEC-induced hepato-, cardio– and nephrotoxicity to predict potential effects of andrographolide (AND), Andrographis herb, Eleutherococcus roots genuine extracts (ES), their fixed combination (AE) and the combination of Rhodiola roots, Schisandra berries and Eleutherococcus roots (RSE) on the organismal level. Methods Gene expression profiling was performed by transcriptome-wide mRNA microarray in the human T98G neuroglia cells after treatment with Adaptogens. 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. Result Significant differences of transcriptome-wide microarray profiles were observed after treatment of T98G cells with FEC and after co-incubation with Adaptogens. FEC induced deregulation of certain genes with suggested toxicity associated with liver fibroses, necrosis and congenital heart diseases. Co-incubation of AE with FEC prevented FEC-induced deregulation of 66 genes increasing organismal death, 37 genes decreasing cell survival, 37 genes decreasing DNA repair, 37 genes decreasing viral infection and some other functions, indicating on potential beneficial effects of AE. Furthermore, FEC-induced hepato-, nephro- and cardiotoxicity related to deregulation of genes was predictably attenuated by AE. Moreover, co-incubation of AE with FEC caused differential expression of genes, which presumably are beneficial for an organism during chemotherapy. They include predicted activation of DNA repair, activation of movement of antigen presenting cells and inhibition of muscle cells death. The main active constituent of AE is AND. Co-incubation of FEC only with AND results in deregulation of 10 genes causing death of breast cancer cells, decrease of liver toxicity and attenuation of organismal death. Co-incubation of ES extract with FEC showed that ES suppressed FEC-induced deregulation of genes, which inhibit organismal death and fertility. Co-incubation of FEC with RSE indicated potential hepatoprotective effect against FEC-induced apoptosis of liver cells presumably due to suppression of FEC-induced expressions of genes, which increased liver cell apoptosis. Simultaneously, RSE activated expression of genes inhibiting tumor growth. Though, microarray analysis did not provide final proof that the genes induced by the AE, AP and ES are responsible for the physiological effects observed in human patients following their oral administration, it provided insights into putative genes and directions for future research and possible implementation into practice. Conclusion Application of cytostatic drugs in combination with Adaptogenic plant extracts induced significant changes in transcriptome-wide microarray profiles of neuroglial cells. These changes indicate on potential beneficial effects of Adaptogens on FEC induced adverse events in cancer chemotherapy.

  • understanding Adaptogenic activity specificity of the pharmacological action of Adaptogens and other phytochemicals
    Annals of the New York Academy of Sciences, 2017
    Co-Authors: Alexander Panossian
    Abstract:

    Adaptogens are stress-response modifiers that increase an organism's nonspecific resistance to stress by increasing its ability to adapt and survive. The classical reductionist model is insufficiently complex to explain the mechanistic aspects of the physiological notion of “adaptability” and the Adaptogenic activity of Adaptogens. Here, I demonstrate that (1) the mechanisms of action of Adaptogens are impossible to rationally describe using the reductionist concept of pharmacology, whereas the network pharmacology approach is the most suitable method; and (2) the principles of systems biology and pharmacological networks appear to be more suitable for conceptualizing Adaptogen function and are applicable to any phytochemical. Molecular targets, signaling pathways, and networks common to Adaptogens have been identified. They are associated with stress hormones and key mediators of the regulation of homeostasis. In this context, the mechanisms of action of Adaptogens are specifically related to stress-protective activity and increased adaptability of the organism. Consequently, Adaptogens exhibit polyvalent beneficial effects against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer, and other aging-related diseases. Current and potential uses of Adaptogens are mainly related to stress-induced fatigue and cognitive function, mental illness, and behavioral disorders. Their prophylactic use by healthy subjects to ameliorate stress and prevent age-related diseases appears to be justified. It is very unlikely that the pharmacological activity of any phytochemical is specific and associated only with one type of receptor, particularly Adaptogenic compounds, which affect key mediators of the adaptive stress response at intracellular and extracellular levels of communication.

  • evaluation of molecular chaperons hsp72 and neuropeptide y as characteristic markers of Adaptogenic activity of plant extracts
    Phytomedicine, 2013
    Co-Authors: Alexzander Asea, Punit Kaur, Alexander Panossian, Karl Georg Wikman
    Abstract:

    Abstract We have previously demonstrated that ADAPT-232, a fixed combination of Adaptogenic substances derived from Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract stimulated the expression and release of neuropeptide Y (NPY) and molecular chaperone Hsp72 from isolated human neurolgia cells. Both of these mediators of stress response are known to play an important role in regulation of neuroendocrine system and immune response. We further demonstrated that ADAPT-232 induced release of Hsp70 is mediated by NPY, suggesting an existence of NPY-mediated pathway of activation of Hsp72 release into the blood circulation system. The objective of this study was to determine whether this pathway is common for Adaptogens and whether NPY and/or Hsp72 can be considered as necessary specific biomarkers for Adaptogenic activity. The release of NPY and Hsp72 from neuroglia cells in response to treatment with various plant extracts ( n  = 23) including selected validated Adaptogens, partly validated Adaptogens, claimed but negligibly validated Adaptogens and some other plant extracts affecting neuroendocrine and immune systems but never considered as Adaptogens was measured using high throughput ELISA techniques. We demonstrated that Adaptogens, e.g. R. rosea , S. chinensis and E. senticosus stimulate both NPY and Hsp70 release from neuroblastoma cells, while tonics and stimulants have no significant effect on NPY in this in vitro test. In the groups of partly validated Adaptogens the effect of Panax ginseng and Withania somnifera was not statistically significant both on NPY and Hsp70 release, while the activating effect of Bryonia alba and Rhaponticum cartamoides was significant only on Hsp70. In contrast, all tested non-Adaptogens, such as antiinflammatoty plant extracts Matricaria recutita , Pelargonium sidoides , Hedera helix and Vitis vinifera significantly inhibit Hsp70 release and have no influence on NPY release from neuroblastoma cells. These experiments were further validated using primary human neurons and confirmed that Adaptogens activate the release of both NPY and Hsp70, while tested non Adaptogens were inactive in NPY assay and inhibit the release of Hsp70. Taken together, our data demonstrates for the first time that neuropeptide Y and heat shock protein Hsp70 can be used as molecular biomarkers for Adaptogenic activity.

  • The Adaptogens Rhodiola and Schizandra Modify the Response to Immobilization Stress in Rabbits by Suppressing the Increase of Phosphorylated Stress-activated Protein Kinase, Nitric Oxide and Cortisol
    SAGE Publishing, 2007
    Co-Authors: Alexander Panossian, Marina Hambardzumyan, Areg Hovhanissyan, Georg Wikman
    Abstract:

    Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of Adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO), cortisol, testosterone, prostaglandin E 2 , leukotriene B 4 and thromboxane B 2 were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the final treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200–300% cf basal levels) following restraint stress, whilst in animals that had received multiple doses of Adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their anti-depressant activity as well as their positive effects on mental performance under stress

V V Neumoin - One of the best experts on this subject based on the ideXlab platform.

A A Spasov - One of the best experts on this subject based on the ideXlab platform.

A Panossian - One of the best experts on this subject based on the ideXlab platform.

  • effects of an Adaptogenic extract on electrical activity of the brain in elderly subjects with mild cognitive impairment a randomized double blind placebo controlled two armed cross over study
    Pharmaceuticals, 2020
    Co-Authors: Wilfried Dimpfel, Leonie Schombert, Ingrid K Keplingerdimpfel, A Panossian
    Abstract:

    Background: The current and potential uses of Adaptogens are mainly related to treatment of stress-induced fatigue, impaired cognitive function, mental illness, and behavioral- and age-related disorders. However, clinical evidence regarding the efficacy of Adaptogens is limited. The primary aim of this study is to determine whether a combination of Adaptogenic plant extracts from Andrographis paniculata and Withania somnifera (Adaptra® Forte) could be used as effective and safe treatment for impaired cognitive, memory, or learning ability functions and sleep disorders. Methods: The changes in electroencephalogram (EEG) frequency ranges in 17 different brain regions, psychometric tests of cognitive performance, as well as standard questionnaires of assessment of mood and sleep were measured after single and repeated administration of Adaptra® or placebo for four weeks and after a two-week treatment-free follow-up period within a randomized, double-blind, placebo-controlled two-armed cross-over study. Results: Adaptra® Forte significantly improved cognitive performance in the d2-Test for attention and the concentration performance test after four weeks’ treatment, and was positively correlated with increases in δ and θ power in the quantitative EEG compared with placebo during cognitive challenges. Conclusion: The results of this study suggest that Adaptra® Forte exhibits a calming and anxiolytic effect without sedation, and is associated with overall stress-protective activity.

  • novel molecular mechanisms for the Adaptogenic effects of herbal extracts on isolated brain cells using systems biology
    Phytomedicine, 2018
    Co-Authors: A Panossian, Thomas Efferth
    Abstract:

    Abstract Introduction Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects Adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. Aim of the study The aim of this study was to identify key molecular mechanisms of Adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola rosea, Eleutherococcus senticosus, Withania somnifera, Rhaponticum carthamoides, and Bryonia alba. Materials and methods To investigate the underlying molecular mechanisms of Adaptogens, we conducted RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of Adaptogens and analyzed the relevance of deregulated genes to adaptive stress-response signaling pathways using in silico pathway analysis software. Results and discussion At least 88 of the 3516 genes regulated by Adaptogens were closely associated with adaptive stress response and adaptive stress-response signaling pathways (ASRSPs), including neuronal signaling related to corticotropin-releasing hormone, cAMP-mediated, protein kinase A, and CREB; pathways related to signaling involving CXCR4, melatonin, nitric oxide synthase, GP6, Gαs, MAPK, neuroinflammation, neuropathic pain, opioids, renin–angiotensin, AMPK, calcium, and synapses; and pathways associated with dendritic cell maturation and G-coupled protein receptor–mediated nutrient sensing in enteroendocrine cells. All samples tested showed significant effects on the expression of genes encoding neurohormones CRH, GNRH, UCN, G-protein–coupled and other transmembrane receptors TLR9, PRLR, CHRNE, GP1BA, PLXNA4, a ligand-dependent nuclear receptor RORA, transmembrane channels, transcription regulators FOS, FOXO6, SCX, STAT5A, ZFPM2, ZNF396, ZNF467, protein kinases MAPK10, MAPK13, MERTK, FLT1, PRKCH, ROS1, TTN), phosphatases PTPRD, PTPRR, peptidases, metabolic enzymes, a chaperone (HSPA6), and other proteins, all of which modulate numerous life processes, playing key roles in several canonical pathways involved in defense response and regulation of homeostasis in organisms. It is for the first time we report that the molecular mechanism of actions of melatonin and plant Adaptogens are alike, all Adaptogens tested activated the melatonin signaling pathway by acting through two G-protein–coupled membrane receptors MT1 and MT2 and upregulation of the ligand-specific nuclear receptor RORA, which plays a role in intellectual disability, neurological disorders, retinopathy, hypertension, dyslipidemia, and cancer, which are common in aging. Furthermore, melatonin activated adaptive signaling pathways and upregulated expression of UCN, GNRH1, TLR9, GP1BA, PLXNA4, CHRM4, GPR19, VIPR2, RORA, STAT5A, ZFPM2, ZNF396, FLT1, MAPK10, MERTK, PRKCH, and TTN, which were commonly regulated by all Adaptogens tested. We conclude that melatonin is an adaptation hormone playing an important role in regulation of homeostasis. Adaptogens presumably worked as eustressors (“stress-vaccines”) to activate the cellular adaptive system by inducing the expression of ASRSPs, which then reciprocally protected cells from damage caused by distress. Functional investigation by interactive pathways analysis demonstrated that Adaptogens activated ASRSPs associated with stress-induced and aging-related disorders such as chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, metabolic disorders, and cancer. Conclusion This study has elucidated the genome-wide effects of several Adaptogenic herbal extracts in brain cells culture. These data highlight the consistent activation of ASRSPs by Adaptogens in T98G neuroglia cells. The extracts affected many genes playing key roles in modulation of adaptive homeostasis, indicating their ability to modify gene expression to prevent stress-induced and aging-related disorders. Overall, this study provides a comprehensive look at the molecular mechanisms by which Adaptogens exerts stress-protective effects.

V B Mandrikov - One of the best experts on this subject based on the ideXlab platform.