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Wikman G.,Swedish Herbal Institute Research and Development
Foundations of Physics | Year: 2013

The notion of order as a universal and fundamental conceptual category is discussed as being based on sets of similar differences and different similarities. A discussion of relationships between order and disorder is followed by a proposal for a mathematical theory based on non-ordinality which could also have relevance for indistinguishables in physics. © 2012 The Author(s). Source


Sarris J.,University of Melbourne | Sarris J.,Swinburne University of Technology | Panossian A.,Swedish Herbal Institute Research and Development | Schweitzer I.,University of Melbourne | And 2 more authors.
European Neuropsychopharmacology | Year: 2011

Research in the area of herbal psychopharmacology has increased markedly over the past decades. To date however, a comprehensive review of herbal antidepressant, anxiolytic and hypnotic psychopharmacology and applications in depression, anxiety and insomnia has been absent. A search of MEDLINE (PubMed), CINAHL, PsycINFO, and the Cochrane Library databases was conducted (up to February 21st 2011) on commonly used psychotropic herbal medicines. A review of the literature was conducted to ascertain mechanisms of action of these botanicals, in addition to a systematic review of controlled clinical trials for treatment of mood, anxiety and sleep disorders, which are common comorbid psychiatric disorders. Specific emphasis was given to emerging phytomedicines. Analysis of evidence levels was conducted, as were effect sizes (Cohen's d) where data were available. Results provided evidence of a range of neurochemical, endocrinological, and epigenetic effects for 21 individual phytomedicines, which are detailed in this paper. Sixty six controlled studies were located involving eleven phytomedicines. Several of these provide a high level of evidence, such as Hypericum perforatum for major depression, and Piper methysticum for anxiety disorders. Several human clinical trials provide preliminary positive evidence of antidepressant effects (Echium amoenum, Crocus sativus, and Rhodiola rosea) and anxiolytic activity (Matricaria recutita, Ginkgo biloba, Passiflora incanata, E. amoenum, and Scutellaria lateriflora). Caution should however be taken when interpreting the results as many studies have not been replicated. Several herbal medicines with in vitro and in vivo evidence are currently unexplored in human studies, and along with use of emerging genetic technologies "herbomics", are areas of potential future research. © 2011 Elsevier B.V. Source


Panossian A.,Swedish Herbal Institute Research and Development | Wikman G.,Swedish Herbal Institute Research and Development | Sarris J.,University of Melbourne | Sarris J.,Swinburne University of Technology
Phytomedicine | Year: 2010

The aim of this review article was to summarize accumulated information related to chemical composition, pharmacological activity, traditional and official use of Rhodiola rosea L. in medicine. In total approximately 140 compounds were isolated from roots and rhizome - monoterpene alcohols and their glycosides, cyanogenic glycosides, aryl glycosides, phenylethanoids, phenylpropanoids and their glycosides, flavonoids, flavonlignans, proanthocyanidins and gallic acid derivatives. Studies on isolated organs, tissues, cells and enzymes have revealed that Rhodiola preparations exhibit adaptogenic effect including, neuroprotective, cardioprotectiv e, anti-fatigue, antidepressive, anxiolytic, nootropic, life-span increasing effects and CNS stimulating activity. A number of clinical trials demonstrate that repeated administration of R. rosea extract SHR-5 exerts an anti-fatigue effect that increases mental performance (particularly the ability to concentrate in healthy subjects), and reduces burnout in patients with fatigue syndrome. Encouraging results exist for the use of Rhodiola in mild to moderate depression, and generalized anxiety. Several mechanisms of action possibly contributing to the clinical effect have been identified for Rhodiola extracts. They include interactions with HPA-system (cortisol-reducing), protein kinases p-JNK, nitric oxide, and defense mechanism proteins (e.g. heat shock proteins Hsp 70 and FoxO/DAF-16). Lack of interaction with other drugs and adverse effects in the course of clinical trials make it potentially attractive for use as a safe medication. In conclusion, Rhodiola rosea has robust traditional and pharmacological evidence of use in fatigue, and emerging evidence supporting cognition and mood. © 2010 Elsevier GmbH. All rights reserved. Source


Panossian A.,Swedish Herbal Institute Research and Development | Hamm R.,Johannes Gutenberg University Mainz | Wikman G.,Swedish Herbal Institute Research and Development | Efferth T.,Johannes Gutenberg University Mainz
Phytomedicine | Year: 2014

Aim The aim of this study was to identify the targets (genes, interactive signaling pathways, and molecular networks) of Rhodiola rosea extract in isolated neuroglia cells and to predict the effects of Rhodiola extract on cellular functions and diseases. In addition, the potential mechanism of action of Rhodiola rosea extract was elucidated, and the "active principle" among the three isolated constituents (salidroside, triandrin, and tyrosol) was identified. Methods Gene expression profiling was performed using the T98G human neuroglia cell line after treatment with the Rhodiola rosea SHR-5 extract and several of its individual constituents (salidroside, triandrin and tyrosol). An interactive pathway analysis of the downstream effects was performed using datasets containing significantly up- and down-regulated genes, and the effects on cellular functions and diseases were predicted. Results In total, the expression of 1062 genes was deregulated by the Rhodiola extract (631 analyzed, 336 - up-regulated, 295 - down-regulated), and 1052, 1062, and 1057 genes were deregulated by salidroside, triandrin, and tyrosol, respectively. The analysis of the downstream effects shows that the most significant effects of Rhodiola are associated with cardiovascular (72 deregulated genes), metabolic (63 genes), gastrointestinal (163 genes), neurological (95 genes), endocrine (60 genes), behavioral (50 genes), and psychological disorders (62 genes). The most significantly affected canonical pathways across the entire dataset, which contains the 1062 genes deregulated by Rhodiola, were the following: (a) communication between innate and adaptive immune cells, (b) eNOS signaling, (c) altered T and B cell signaling in rheumatoid arthritis, (d) axonal guidance signaling, (e) G-protein coupled receptor signaling, (f) glutamate receptor signaling, (g) ephrin receptor signaling, (h) cAMP-mediated, and (i) atherosclerosis signaling pathways. Genes associated with behavior and behavioral diseases were identified within intracellular signaling pathways (d) through (h). The analysis of the downstream effects predicted decreases in emotional and aggressive behavior, which corroborates the results from preclinical and clinical studies of the use of Rhodiola for the treatment of depression and anxiety. Of the 17 genes that regulate emotional behavior, nine exhibit expression patterns that are consistent with decreases in emotional behavior (z-score -2.529), and all five relevant genes are expressed in a manner consistent with decreases in aggressive behavior (z-score -2.197). A decrease in seizures and infarct sizes and an increase in the chemotaxis of cells were predicted to accompany the decrease in emotional and aggressive behaviors. Conclusions Rhodiola exhibits a multi-targeted effect on transcription to regulate the cellular response, affecting the various signaling pathways and molecular networks associated with beneficial effects on emotional behavior, particularly aggressive behavior, and with psychological, neurological, cardiovascular, metabolic, endocrine, and gastrointestinal disorders. Each of the purified compounds has its own pharmacological profile, which is both similar to and different from that of the total Rhodiola extract. In general, several compounds contribute to the specific cellular or/and physiological function of the extract in various diseases. © 2014 Elsevier GmbH. All rights reserved. Source


Panossian A.,Swedish Herbal Institute Research and Development | Seo E.-J.,Johannes Gutenberg University Mainz | Wikman G.,Swedish Herbal Institute Research and Development | Efferth T.,Johannes Gutenberg University Mainz
Phytomedicine | Year: 2015

Background Generally accepted, but insufficiently proved, the concept of synergy is based on an assumption that combining of two biologically active substances is justified because the combination is more active and less harmful than the ingredients. Hypothesis Analysis of RNA microarray of isolated neuroglia cells and the comparison the number of genes deregulated by plant extracts and their fixed herbal formulation might be a useful tool/method for assessment of synergistic and antagonistic interactions of herbal extracts in human organism. Aim The primary aim of this study was to extend a new method of assessment of synergistic and antagonistic interactions of herbal extracts in isolated human neuroglia cells when they applied in the form of fixed combinations. The secondary aim of the study was to predict possible effects of Herba Andrographidis (APE), Radix Eleutherococci (ESE) genuine extracts and their fixed combination Kan Jang (KJ) on cellular and physiological functions and associated diseases. The third task of the study was to find evidences that justify the hypothesis that these plants extracts in combination are more useful than the monodrugs. Methods Gene expression profiling was performed on the human neuroglia cell line T98G after treatment with APE, ESE, KJ and total number of more than two fold-deregulated genes from all experiments were compared by Venn diagram. 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 ESE and APE significantly deregulate 207 and 211 genes correspondingly; 36 deregulated genes were common for both extracts. In total of 382 deregulated genes was expected to be deregulated by their fixed combination KJ. However, it was found only 250 genes deregulated by KJ. Among these 250 genes, 111 genes were unique for the KJ combination and not affected by ESE and APE. This is presumably due to synergistic interactions of molecular networks affected by ESE and APE. Meanwhile, 170 genes deregulated by ESE, and 55 genes deregulated by APE when tested alone, were not up- or downregulated by KJ. That is the result of antagonistic integrations of ESE and APE extracts when applied in the combination. Fold change of expression of 18 common genes deregulated by APE, ESE and KJ was not additive when APE and ESE are combined in KJ herbal formula. However, a qualitative difference is observed in the fingerprint of deregulated genes of daughter substance (KJ) compared to fingerprints/signatures of deregulated genes of parent substances (APE and ESE). Specific for KJ and predictable (z-score > 2) were the effects on pathways and networks associated with infectious and chronic inflammatory disorders, namely encephalitis or neurological movement disorders. Noteworthy, Eleutherococcus alone has no effect on those networks, particularly on encephalitis network, while KJ deregulates 11 genes which have predictable inhibitory effect on infection, while APE regulates only 5 genes which are activated in encephalitis. It can be speculated that APE in combination with ESE may have better therapeutic effect, since more targets are affected. Similar suggestion is justified regarding neurological movement, which is associated with chronic inflammation, like arthritis and osteoarthrosis. Though, microarray analysis did not provide final proof that the genes induced by the KJ, APE and ESE are responsible for the physiological effects observed in humans following their oral administration. It provided insights into putative genes and directions for future research and possible implementation into practice. The most significantly affected canonical pathways deregulated by KJ and APE was interferon signaling pathway, indicating the possible effectiveness of KJ and APE in the treatment of severe sepsis, systemic lupus erythematosus and other autoimmune diseases Conclusion Analysis of RNA microarray data from isolated neuroglia cells and the comparison the number of genes deregulated by plant extracts and their fixed herbal formulation might be a useful tool/method for assessment of synergistic and antagonistic interactions of herbal extracts in human organism. Combination of APE and ESE in KJ formulation is most likely justified. © 2015 Elsevier GmbH. All rights reserved. Source

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