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      Cordyceps – A traditional Chinese medicine and another fungal therapeutic biofactory?

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          Graphical abstract

          (a) The Yin and Yang symbol: The philosophical basis of some of the assumed properties and research on Cordyceps (see text)? (b) Cordyceps spp. parasitizing a dead Campanotus insect and (c) cordyheptapeptide A, a natural product from the fungus.

          Abstract

          Traditional Chinese medicines (TCM) are growing in popularity. However, are they effective? Cordyceps is not studied as systematically for bioactivity as another TCM, Ganoderma. Cordyceps is fascinating per se, especially because of the pathogenic lifestyle on Lepidopteron insects. The combination of the fungus and dead insect has been used as a TCM for centuries. However, the natural fungus has been harvested to the extent that it is an endangered species. The effectiveness has been attributed to the Chinese philosophical concept of Yin and Yang and can this be compatible with scientific philosophy? A vast literature exists, some of which is scientific, although others are popular myth, and even hype. Cordyceps sinensis is the most explored species followed by Cordyceps militaris. However, taxonomic concepts were confused until a recent revision, with undefined material being used that cannot be verified. Holomorphism is relevant and contamination might account for some of the activity. The role of the insect has been ignored. Some of the analytical methodologies are poor. Data on the “old” compound cordycepin are still being published: ergosterol and related compounds are reported despite being universal to fungi. There is too much work on crude extracts rather than pure compounds with water and methanol solvents being over-represented in this respect (although methanol is an effective solvent). Excessive speculation exists as to the curative properties. However, there are some excellent pharmacological data and relating to apoptosis. For example, some preparations are active against cancers or diabetes which should be fully investigated. Polysaccharides and secondary metabolites are of particular interest. The use of genuine anamorphic forms in bioreactors is encouraged.

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          Control of apoptosis by p53.

          The p53 tumor suppressor acts to integrate multiple stress signals into a series of diverse antiproliferative responses. One of the most important p53 functions is its ability to activate apoptosis, and disruption of this process can promote tumor progression and chemoresistance. p53 apparently promotes apoptosis through transcription-dependent and -independent mechanisms that act in concert to ensure that the cell death program proceeds efficiently. Moreover, the apoptotic activity of p53 is tightly controlled, and is influenced by a series of quantitative and qualitative events that influence the outcome of p53 activation. Interestingly, other p53 family members can also promote apoptosis, either in parallel or in concert with p53. Although incomplete, our current understanding of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor network controlled by different signals, environmental factors, and cell type. Understanding this network in more detail will provide insights into cancer and other diseases, and will identify strategies to improve their therapeutic treatment.
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            Phylogenetic classification of Cordyceps and the clavicipitaceous fungi

            Cordyceps, comprising over 400 species, was historically classified in the Clavicipitaceae, based on cylindrical asci, thickened ascus apices and filiform ascospores, which often disarticulate into part-spores. Cordyceps was characterized by the production of well-developed often stipitate stromata and an ecology as a pathogen of arthropods and Elaphomyces with infrageneric classifications emphasizing arrangement of perithecia, ascospore morphology and host affiliation. To refine the classification of Cordyceps and the Clavicipitaceae, the phylogenetic relationships of 162 taxa were estimated based on analyses consisting of five to seven loci, including the nuclear ribosomal small and large subunits (nrSSU and nrLSU), the elongation factor 1α (tef1), the largest and the second largest subunits of RNA polymerase II (rpb1 and rpb2), β-tubulin (tub), and mitochondrial ATP6 (atp6). Our results strongly support the existence of three clavicipitaceous clades and reject the monophyly of both Cordyceps and Clavicipitaceae. Most diagnostic characters used in current classifications of Cordyceps (e.g., arrangement of perithecia, ascospore fragmentation, etc.) were not supported as being phylogenetically informative; the characters that were most consistent with the phylogeny were texture, pigmentation and morphology of stromata. Therefore, we revise the taxonomy of Cordyceps and the Clavicipitaceae to be consistent with the multi-gene phylogeny. The family Cordycipitaceae is validated based on the type of Cordyceps, C. militaris, and includes most Cordyceps species that possess brightly coloured, fleshy stromata. The new family Ophiocordycipitaceae is proposed based on Ophiocordyceps Petch, which we emend. The majority of species in this family produce darkly pigmented, tough to pliant stromata that often possess aperithecial apices. The new genus Elaphocordyceps is proposed for a subclade of the Ophiocordycipitaceae, which includes all species of Cordyceps that parasitize the fungal genus Elaphomyces and some closely related species that parasitize arthropods. The family Clavicipitaceae s. s. is emended and includes the core clade of grass symbionts (e.g., Balansia, Claviceps, Epichloë, etc.), and the entomopathogenic genus Hypocrella and relatives. In addition, the new genus Metacordyceps is proposed for Cordyceps species that are closely related to the grass symbionts in the Clavicipitaceae s. s. Metacordyceps includes teleomorphs linked to Metarhizium and other closely related anamorphs. Two new species are described, and lists of accepted names for species in Cordyceps, Elaphocordyceps, Metacordyceps and Ophiocordyceps are provided.
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              Ganoderma - a therapeutic fungal biofactory.

              Ganoderma is a basidiomycete white rot fungus which has been used for medicinal purposes for centuries particularly in China, Japan and Korea. A great deal of work has been carried out on Ganoderma lucidum. The common names for preparations include Lingzhi, Munnertake, Sachitake, Reishi and Youngzhi. This review collates the publications detailing activities and compounds by representative species whilst considering the most valid claims of effectiveness. The biological activities reported of preparations from Ganoderma are remarkable and given most emphasis herein as distinct from structure/activity information. The metabolites consist of mainly polysaccharides and terpenoids. Many are activities against the major diseases of our time and so the present review is of great importance. The list of effects is huge ranging from anti-cancer to relieving blockages of the bladder. However, the reports have not all been tested scientifically with the convincing evidence is reserved for assays of pure compounds. It is a prime example of an ancient remedy being of great relevance to the modern era. There does appear to be an assumption that the therapeutic effects attributed to the fungus have been proven. The next step is to produce some effective medicines which may be hampered by problems of mass production.
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                Author and article information

                Contributors
                Journal
                Phytochemistry
                Phytochemistry
                Phytochemistry
                Elsevier Ltd.
                0031-9422
                1873-3700
                17 March 2008
                May 2008
                17 March 2008
                : 69
                : 7
                : 1469-1495
                Affiliations
                Institute for Biotechnology and Bioengineering (IBB), Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal
                Author notes
                [* ]Tel.: +351 253 604 400; fax: +351 253 678 986. russell.paterson@ 123456deb.uminho.pt
                Article
                S0031-9422(08)00042-3
                10.1016/j.phytochem.2008.01.027
                7111646
                18343466
                8304b1f0-155c-4937-8db6-4ff759a73160
                Copyright © 2008 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 17 December 2007
                : 17 January 2008
                Categories
                Article

                Biochemistry
                fungus,cordyceps sinensis,cordyceps militaris,lepidopteron,traditional chinese medicine,cancer,diabetes,apoptosis

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