Cordyceps: Alleviating ischemic cardiovascular and cerebrovascular injury - A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps has a long medicinal history as a nourishing herb in traditional Chinese medicine (TCM). Ischemic cardio-cerebrovascular diseases (CCVDs), including cerebral ischemic/reperfusion injury (CI/RI) and myocardial ischemic/reperfusion injury (MI/RI), are major contributors to mortality and disability in humans. Numerous studies have indicated that Cordyceps or its artificial substitutes have significant bioactivity on ischemic CCVDs, however, there is a lack of relevant reviews. AIM OF THE STUDY: This review was conducted to investigate the chemical elements, pharmacological effects, clinical application and drug safety of Cordycepson ischemic CCVDs. MATERIALS AND METHODS: A comprehensive search was conducted on the Web of Science, PubMed, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases using the keywords "Cordyceps", "Cerebral ischemic/reperfusion injury", and "Myocardial ischemic/reperfusion injury" or their synonyms. The retrieved literature was then categorized and summarized. RESULTS: The study findings indicated that Cordyceps and its bioactive components, including adenosine, cordycepin, mannitol, polysaccharide, and protein, have the potential to protect against CI/RI and MI/RI by improving blood perfusion, mitigating damage from reactive oxygen species, suppressing inflammation, preventing cellular apoptosis, and promoting tissue regeneration. Individually, Cordyceps could reduce neuronal excitatory toxicity and blood-brain barrier damage caused by cerebral ischemia. It can also significantly improve cardiac energy metabolism disorders and inhibit calcium overload caused by myocardial ischemia. Additionally, Cordyceps exerts a significant preventive or curative influence on the factors responsible for heart/brain ischemia, including hypertension, thrombosis, atherosclerosis, and arrhythmia. CONCLUSION: This study demonstrates Cordyceps' prospective efficacy and safety in the prevention or treatment of CI/RI and MI/RI, providing novel insights for managing ischemic CCVDs.

Cordythiazole A, the first member of thiazole alkaloids from Chinese cordyceps, with α-glucosidase inhibitory activity.

Chinese cordyceps, also known as Dong-Chong-Xia-Cao, is widely recognized as a famous precious tonic herb, and used as traditional Chinese medicine for centuries. It is mainly used for regulating the immune system and improving functions of the lung and kidney, with anti-tumor, anti-inflammatory, and anti-diabetic activities. Due to its rarity and preciousness, a few chemical components are isolated and identified. Moreover, most of them are common chemical components and widely distributed in other natural resources, such as nucleosides, sterols, fatty acids, sugar alcohols, and peptides. Therefore, a large number of active substances of Chinese cordyceps is still unclear. During our search for chemical constituents of Chinese cordyceps, a new thiazole alkaloid, cordythiazole A (1), was isolated and identified. Its structure was elucidated by comprehensive spectroscopic analysis and single-crystal X-ray diffraction analysis. This is the first report of the presence of thiazole alkaloid in Chinese cordyceps, which adds a new class of metabolite of Chinese cordyceps. Furthermore, a putative biosynthesis pathway of cordythiazole A was proposed based on possible biogenic precursor, genes, and literatures. In addition, it showed α-glucosidase inhibitory activity with potency close to that of acarbose. The discovery of cordythiazole A with α-glucosidase inhibitory activity adds a new class of potential anti-diabetes ingredient in Chinese cordyceps.

Chinese Cordyceps: Bioactive Components, Antitumor Effects and Underlying Mechanism-A Review.

Chinese Cordyceps is a valuable source of natural products with various therapeutic effects. It is rich in various active components, of which adenosine, cordycepin and polysaccharides have been confirmed with significant immunomodulatory and antitumor functions. However, the underlying antitumor mechanism remains poorly understood. In this review, we summarized and analyzed the chemical characteristics of the main components and their pharmacological effects and mechanism on immunomodulatory and antitumor functions. The analysis revealed that Chinese Cordyceps promotes immune cells' antitumor function by via upregulating immune responses and downregulating immunosuppression in the tumor microenvironment and resetting the immune cells' phenotype. Moreover, Chinese Cordyceps can inhibit the growth and metastasis of tumor cells by death (including apoptosis and autophagy) induction, cell-cycle arrest, and angiogenesis inhibition. Recent evidence has revealed that the signal pathways of mitogen-activated protein kinases (MAPKs), nuclear factor kappaB (NF-κB), cysteine-aspartic proteases (caspases) and serine/threonine kinase Akt were involved in the antitumor mechanisms. In conclusion, Chinese Cordyceps, one type of magic mushroom, can be potentially developed as immunomodulator and anticancer therapeutic agents.

The invasion process of the entomopathogenic fungus Ophiocordyceps sinensis into the larvae of ghost moths (Thitarodes xiaojinensis) using a GFP-labeled strain.

Chinese cordyceps is a well-known and valuable traditional Chinese medicine that forms after Ophiocordyceps sinensis parasitizes ghost moth larvae. The low natural infection rate of O. sinensis limits large-scale artificial cultivation of Chinese cordyceps, and the invasion process is unclear. To investigate the temporal and spatial regulation when O. sinensis enters ghost moths, we constructed an O. sinensis transformant that stably expresses green fluorescent protein (GFP). Inoculating Thitarodes xiaojinensis larvae with a high concentration of GFP-labeled O. sinensis, we observed that O. sinensis conidia could adhere to the host cuticle within 2 days, germinate penetration pegs within 4 days, and produce blastospores in the host hemocoel within 6 days. The reconstructed three-dimensional (3D) structures of the invasion sites showed that penetration pegs germinated directly from O. sinensis conidia at the joining site with the larval cuticle. Differentiated appressoria or hyphae along the host epicuticle are not required for O. sinensis to invade ghost moths. Overall, the specific invasion process of O. sinensis into its host is clarified, and we provided a new perspective on the invasion process of entomopathogenic fungi.

Immulectin-2 from the ghost moth, Thitarodes xiaojinensis (Lepidoptera: Hepialidae), modulates cellular and humoral responses against fungal infection.

C type-lectins constitute a large family of pattern recognition receptors, playing important roles in insect immune defenses. Thitarodes xiaojinensis larvae showed distinct immune features after Ophiocordyceps sinensis, Cordyceps militaris, or Beauveria bassiana infection. Based on transcriptome and immunoblot analysis, we found that immulectin-2 (IML2) was induced after T. xiaojinensis larvae were infected by C. militaris or B. bassiana but maintained at a low level after larvae injected with O. sinensis or Ringer's buffer. Recombinant IML2 (rIML2) could promote melanization, encapsulation, phagocytosis, and hemocyte aggregation in vitro. RNA interference with IML2 induced a significant reduction in the transcript levels of various antimicrobial peptides. Importantly, we found that the abundance of O. sinensis blastospores coated with rIML2 dramatically decreased in the host hemolymph. Overall, this study demonstrated that T. xiaojinensis IML2 modulates cellular and humoral responses to entomopathogenic fungi, broadening our view of the immune interaction between O. sinensis and its host.

Discovery of the signal pathways and major bioactive compounds responsible for the anti-hypoxia effect of Chinese cordyceps.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypoxia will cause an increase in the rate of fatigue and aging. Chinese cordyceps, a parasitic Thitarodes insect-Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, has long been used to ameliorate human conditions associated with aging and senescence, it is principally applied to treat fatigue, night sweating and other symptoms related to aging, and it may play the anti-aging and anti-fatigue effect by improving the body's hypoxia tolerance. AIMS OF THE STUDY: The present study investigated the anti-hypoxia activity of Chinese cordyceps and explore the main corresponding signal pathways and bioactive compounds. MATERIALS AND METHODS: In this study, network pharmacology analysis, molecular docking, cell and whole pharmacodynamic experiments were hired to study the major signal pathways and the bioactive compounds of Chinese cordyceps for anti-hypoxia activity. RESULTS: 17 pathways which Chinese cordyceps acted on seemed to be related to the anti-hypoxia effect, and "VEGF signal pathway" was one of the most important pathway. Chinese cordyceps improved the survival rate and regulated the targets related VEGF signal pathway of H9C2 cells under hypoxia, and also had significant anti-hypoxia effects to mice. Chorioallantoic membrane model experiment showed that Chinese cordyceps and the main constituents of (9Z,12Z)-octadeca-9,12-dienoic acid and cerevisterol had significant angiogenic activity in hypoxia condition. CONCLUSION: Based on the results of network pharmacology and molecular docking analysis, cell and whole pharmacodynamic experiments, promoting angiogenesis by regulating VEGF signal pathway might be one of the mechanisms of anti-hypoxia effect of Chinese cordyceps, (9Z, 12Z)-octadeca-9,12-dienoic acid and cerevisterol were considered as the major anti-hypoxia bioactive compounds in Chinese cordyceps.

Arsenic transfer along the soil-sclerotium-stroma chain in Chinese cordyceps and the related health risk assessment.

BACKGROUND: Chinese cordyceps (Lepidoptera: Ophiocordyceps sinensis)is a larval-fungus complex. The concentration and distribution of arsenic (As) may vary during the stroma (ST) germination process and between the sclerotium (SC) and the ST. The soil-to-Chinese cordyceps system is an environmental arsenic exposure pathway for humans. We studied the As concentration in the soil, the SC, and the ST of Chinese cordyceps, and performed a risk assessment. METHODS: Soil and Chinese cordyceps samples were collected from the Tibetan Plateau in China. The samples were analyzed for the total As concentration and As species determination, which were conducted by inductively coupled plasma mass spectrometry (ICP-MS) and HPLC-ICP-MS, respectively. RESULTS: The concentration of total As in the soil was much higher than in SC and ST. The major As species in the soil was inorganic AsV. In SC and ST, organic As was predominant, and the majority of As was an unknown organic form. There are significant differences in the As distribution and composition in soil, SC, and ST. Our risk assessment indicated that chronic daily ingestion was higher than inhalation and dermal exposure in children and adults. The hazard index (HI) of the non-carcinogenic and cancer risks (CR) for human health were HI ≤ 1 and CR < 1 × 10-4, respectively. CONCLUSION: The Chinese cordyceps possesses highly-efficient detoxifying characteristics and has a significant role in As transformation during its life cycle. We found that the levels of As in soils from the habitat of Chinese cordyceps were higher than the soil background values in China, but the probability for incurring health risks remained within the acceptable levels for humans.

Toxicological safety evaluation of the cultivated Chinese cordyceps.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese cordyceps, a parasitic Thitarodes insect-Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, is one of the most valuable traditional Chinese medicines and health food for ameliorating conditions associated with aging and for treating fatigue, night sweats, hyperglycemia, hyperlipidemia, respiratory, renal and liver diseases, and hyposexuality. The natural Chinese cordyceps resource is rare due to its harsh growing environment, limited geographical distribution and global climate warming. Artificial cultivation of Chinese cordyceps has been successfully established to meet its high demand in market. AIMS OF THE STUDY: The present study aims to evaluate the toxicological safety of the cultivated Chinese cordyceps and provide scientific data for subsequent development and utilization of this valuable biological resource. MATERIALS AND METHODS: The Chinese cordyceps was cultivated by mimicking the habitat environment in low-altitude areas and identified by morphological and microscopic characteristics. Its phytochemical profile was determined by the HPLC. Toxicological studies based on the cultivated Chinese cordyceps were conducted, including chromosomal aberration test of Chinese hamster lung (CHL) cells, Ames test, acute toxicity test and micronucleus (MN) test of bone marrow cells. RESULTS: The Chinese cordyceps successfully cultivated in low-altitude areas exhibited the same morphological and microscopic characteristics as natural Chinese cordyceps. The adenosine content was in accordance with the Chinese Pharmacopoeia (2015 Edition). The HPLC fingerprint was determined and five main chromatographic peaks representing uracil, uridine, inosine, guanosine and adenosine were identified. No dose-dependent increase in the rates of chromosomal aberration was detected in the presence or absence of metabolic activation system. Ames test also demonstrated no dose-dependent increase in the number of reversion mutation for five bacterial strains, with or without rat liver microsomal enzyme mixture (S9) metabolic activation, at a quantity range of 128-5000 µg cultivated Chinese cordyceps per plate. The acute toxicity test with mice showed that after 20 g/kg oral administration of cultivated Chinese cordyceps, neither animal death nor any abnormal change in general dissection of various tissues and organs of the animals were found within 14 days. The median lethal dose (LD50) was greater than 5 g/kg, which is regarded as a non-toxic level, and maximum tolerable dose (MTD) of cultivated Chinese cordyceps in ICR mice was more than 20 g/kg. MN test of mouse bone marrow cells indicated no significant differences among each sample dose and the negative control. CONCLUSION: Based on the results from four toxicological tests, it was concluded that the cultivated Chinese cordyceps was classified as non-toxic in one single administration at high doses by intragastric route in mice. This study provides scientific experimental basis for its safety.

Infection of Ophiocordyceps sinensis Fungus Causes Dramatic Changes in the Microbiota of Its Thitarodes Host.

The Chinese cordyceps is a unique and valuable parasitic complex of Thitarodes/Hepialus ghost moths and the Ophiocordyceps sinensis fungus for medicine and health foods from the Tibetan Plateau. During artificial cultivation of Chinese cordyceps, the induction of blastospores into hyphae is a prerequisite for mummification of the infected Thitarodes larvae. To explore the microbial involvement in the induction of mycelia-blastospore transition, the microbiota of the hemolymph and gut from Thitarodes xiaojinensis larvae with or without injected O. sinensis blastospores were investigated by culture-dependent and -independent methods. Twenty-five culturable bacterial species and 14 fungal species, together with 537 bacterial operational taxonomic units (OTUs) and 218 fungal OTUs, were identified from the hemolymph and gut of samples from five stages including living larvae without injected fungi (A) or with high blastospore load (B), mummifying larvae without mycelia coating (C), freshly mummifying larvae coated with mycelia (D), and completely mummified larvae with mycelia (E). Two culturable bacterial species (Serratia plymuthica, Serratia proteamaculans), and 47 bacterial and 15 fungal OTUs were considered as shared species. The uninfected larval hemolymph contained 13 culturable bacterial species but no fungal species, together with 164 bacterial and 73 fungal OTUs. To our knowledge, this is the first study to detect large bacterial communities from the hemolymph of healthy insect larvae. When the living larvae contained high blastospore load, the culturable bacterial community was sharply inhibited in the hemolymph but the bacterial and fungal community greatly increased in the gut. In general, high blastospore load increased bacterial diversity but sharply decreased fungal diversity in the hemolymph and gut by OTUs. The bacterial loads of four culturable species (Chryseobacterium sp., Pseudomonas fragi, S. plymuthica, S. proteamaculans) increased significantly and O. sinensis and Pseudomonas spp. became dominant microbes, when the infected larvae became mummified, indicating their possible involvement in the larval mummification process. The discovery of many opportunistic pathogenic bacteria in the hemolymph of the healthy larvae, the larval microbial diversity influenced by O. sinensis challenge and the involvement of dominant bacteria during larval mummification process provide new insight into the infection and mummification mechanisms of O. sinensis in its Thitarodes hosts.

Analysis of Volatile Components in Different Ophiocordyceps sinensis and Insect Host Products.

The artificial production of Ophiocordyceps sinensis mycelia and fruiting bodies and the Chinese cordyceps has been established. However, the volatile components from these O. sinensis products are not fully identified. An efficient, convenient, and widely used approach based on headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography and quadrupole time-of-flight mass spectrometry (GC×GC-QTOFMS) was developed for the extraction and the analysis of volatile compounds from three categories of 16 products, including O. sinensis fungus, Thitarodes hosts of O. sinensis, and the Chinese cordyceps. A total of 120 volatile components including 36 alkanes, 25 terpenes, 17 aromatic hydrocarbons, 10 ketones, 5 olefines, 5 alcohols, 3 phenols, and 19 other compounds were identified. The contents of these components varied greatly among the products but alkanes, especially 2,5,6-trimethyldecane, 2,3-dimethylundecane and 2,2,4,4-tetramethyloctane, are the dominant compounds in general. Three categories of volatile compounds were confirmed by partial least squares-discriminant analysis (PLS-DA). This study provided an ideal method for characterizing and distinguishing different O. sinensis and insect hosts-based products.

Internal and External Microbial Community of the Thitarodes Moth, the Host of Ophiocordyceps sinensis.

Ophiocordyceps sinensis is a widely known medicinal entomogenous fungus, which parasitizes the soil-borne larva of Thitarodes (Hepialidae, Lepidoptera) distributed in the Qinghai-Tibetan Plateau and its adjacent areas. Previous research has involved artificial cultivation of Chinese cordyceps (the fungus-caterpillar complex), but it is difficult to achieve large-scale cultivation because the coupling relation between the crucial microbes and their hosts is not quite clear. To clarify the influence of the internal microbial community on the occurrence of Chinese cordyceps, in this study, the unfertilized eggs of Thitarodes of different sampling sites were chosen to analyze the bacterial and fungal communities via 16S rRNA and ITS sequencing for the first time. The results showed that for bacteria, 348 genera (dominant genera include Wolbachia, Spiroplasma, Carnobacterium, Sphingobium, and Acinetobacter) belonging to 26 phyla (dominant phyla include Proteobacteria, Firmicutes, Tenericutes, Actinobacteria, Acidobacteria, and Bacteroidetes), 58 classes, 84 orders, and 120 families were identified from 1294 operational taxonomic units (OTUs). The dominant bacterial genus (Spiroplasma) may be an important bacterial factor promoting the occurrence of Chinese cordyceps. For fungi, 289 genera, mainly including Aureobasidium, Candida, and Cryptococcus, were identified, and they belonged to 5 phyla (Ascomycota, Basidiomycota, Chytridiomycota, Glomeromycota, and Zygomycota), 26 classes, 82 orders, and 165 families. Eight bacterial OTUs and 12 fungal OTUs were shared among all of the detected samples and were considered as core species. Among them, Wolbachia, Spiroplasma, Carnobacterium, Aureobasidium, and Phoma may play important roles in helping the host larva to digest foods, adapt to extreme environments, or resist pathogens. On the other hand, the external (soil) microbial community was synchronously and comparatively analyzed. Comparative analysis revealed that external microbial factors might play a more significant role in the occurrence of Chinese cordyceps, owing to the significant differences revealed by α-diversity and ß-diversity analyses among different groups. In summary, the results of this study may contribute to the large-scale cultivation of Chinese cordyceps.

Diversity and Co-Occurrence Patterns of Soil Bacterial and Fungal Communities of Chinese Cordyceps Habitats at Shergyla Mountain, Tibet: Implications for the Occurrence.

Chinese Cordyceps is a well-known medicinal larva-fungus symbiote distributed in the Qinghai-Tibetan Plateau and adjacent areas. Previous studies have involved its artificial cultivation but commercial cultivation is difficult to perform because the crucial factors triggering the occurrence of Chinese Cordyceps are not quite clear. The occurrence of Chinese Cordyceps is greatly affected by the soil environment, including the soil's physicochemical and microecological properties. In this study, the effects of these soil properties on the occurrence of Chinese Cordyceps were investigated. The results show that the physicochemical properties, including easily oxidizable organic carbon (EOC), soil organic carbon (SOC), humic acid carbon (HAC), humin carbon (HMC), and pH, might be negatively related to the occurrence of Chinese Cordyceps, and soil water content (SWC) might be positively related. Several soil physicochemical parameters (pH, SOC, HMC, HAC, available potassium (APO), available phosphorus (APH), microbial biomass carbon (MBC), and the ratio of NH4+ to NO3- (NH4+/NO3-)) and microbial properties interact and mix together, which might affect the occurrence of Chinese Cordyceps. Soil microbial community structure was also a possible factor, and a low level of bacterial and fungal diversity was suitable for the occurrence of Chinese Cordyceps. The intra-kingdom network revealed that a closer correlation of the bacterial community might help the occurrence of Chinese Cordyceps, while a closer correlation of the fungal community might suppress it. The inter-kingdom network revealed that the occurrence rate of Chinese Cordyceps might be negatively correlated with the stability of the correlation state of the soil habitat. In conclusion, this study shows that soil physicochemical properties and microbial communities could be greatly related with the occurrence of Chinese Cordyceps. In addition, soil physicochemical properties, the level of bacterial and fungal diversity, and correlations of bacterial and fungal communities should be controlled to a certain level to increase the production of Chinese Cordyceps in artificial cultivation.

Composition and predictive functional analysis of bacterial communities inhabiting Chinese Cordyceps insight into conserved core microbiome.

BACKGROUND: Over the past few decades, most attention to Chinese Cordyceps-associated endogenous microorganism was focused on the fungal community that creates critical bioactive components. Bacterial community associated with Chinese Cordyceps has been previously described; however, most studies were only presenting direct comparisons in the Chinese Cordyceps and its microenvironments. In the current study, our objectives were to reveal the bacterial community structure composition and predict their function. RESULTS: We collected samples of Chinese Cordyceps from five sites located in the Qinghai-Tibet Plateau and used a high throughput sequencing method to compare Chinese Cordyceps-associated bacterial community composition and diversity quantitatively across sites. The results indicated that for the Chinese Cordyceps-associated bacterial community there is no single core microbiome, which was dominated by the both Proteobacteria and Actinobacteria. Predictive functional profiling suggested a location specific function pattern for Chinese Cordyceps and bacteria in the external mycelial cortices involved in the biosynthesis of active constituents. CONCLUSIONS: This study is firstly used high throughput sequencing method to compare the bacterial communities inhabiting Chinese Cordyceps and its microhabitat and to reveal composition functional capabilities of the bacteria, which will accelerate the study of the functions of bacterial communities in the micro-ecological system of Chinese Cordyceps.

A breakthrough in the artificial cultivation of Chinese cordyceps on a large-scale and its impact on science, the economy, and industry.

Chinese cordyceps, an entity of the Chinese caterpillar fungus (Ophiocordyceps sinensis, syn. Cordyceps sinensis) that parasitizes ghost moth larvae, is one of the best known traditional Chinese medicines and is found exclusively on the Tibetan Plateau with limited natural resources. Although the fungus O. sinensis can grow on artificial substrates and the ghost moth has been successfully reared, the large-scale artificial cultivation of Chinese cordyceps has only recently been accomplished after several decades of efforts and attempts. In this article, research progress related to this breakthrough from living habitats, the life history of the fungus, its host insect, fungal isolation and culture, host larvae rearing, infection cycle of the fungus to the host, primordium induction, and fruiting body development have been reviewed. An understanding of the basic biology of O. sinensis, its host insect and the simulation of the Tibetan alpine environment resulted in the success of artificial cultivation on a large scale. Practical workshop production has reached annual yields of 2.5, 5, and 10 tons in 2014, 2015, and 2016, respectively. There was no difference in the chemical components detected between the cultivated and natural Chinese cordyceps. However, the artificial cultivation system can be controlled to avoid heavy metal contamination and results in high-quality products. Although omics studies, including genomic, transcriptomic, proteomic, and metabolomic studies, have helped to understand the biology of the fungus, the success of the artificial cultivation of the Chinese cordyceps is clearly a milestone and provides the possibility for research on the in-depth mechanisms of the interaction between the fungus and host insects and their adaptation to the harsh habitats. This cultivation will not only result in a large industry to alleviate the pressure of human demand but also protect the limited natural resources for sustainable utilization.

Cordyceps industry in China.

Cordyceps, as a general term, describes a group of ascomycetous fungi growing on arthropods and other related fungi. Some cordyceps have been used in traditional Chinese medicine for centuries and cordyceps-derived products are currently a big industry in China. A number of medicinal and health products have been developed and extensively commercialized from natural Chinese cordyceps, its anamorphic fungus (Hirsutella sinensis), and other fungi known as Chinese cordyceps. The lack of a defined classification system for medicinal cordyceps fungi is a source of confusion in the industry and the public, and even among pharmaceutical scientists. This review summarizes the cordyceps fungi currently used in the industry in China with a special reference to clarify Chinese cordyceps and associated fungi. Cordyceps militaris, Cordyceps guangdongensis and Isaria cicadae are well recognized and commercialized cordyceps fungi in China. Except the natural Chinese cordyceps and its anamorphic fungus, Paecilomyces hepiali, Mortierella hepiali, Cephalosporium sinensis and Clonostachys rosea isolated from natural Chinese cordyceps are classified as Chinese cordyceps-associated fungi. P. hepiali is a cordyceps fungus based on current phylogenetic analysis of Hypocreales, while M. hepiali is a fungus in the Zygomycetes and should only be treated as associated fungus of Chinese cordyceps. C. sinensis and C. rosea belong to the Hypocreales and their relationship to cordyceps fungi should be further studied. The exploitation of the resources of cordyceps fungi and their quality control in the industry should be major topics for future studies. Cooperation between the industry and the research community will enhance the whole cordyceps industry.