Keywords

1 Introduction

Caterpillar mushroom, Cordyceps militaris (L.) Fr., (Cordycipitaceae, Ascomycetes), is one of the popular edible and medicinal fungi. It is the type species of the modified genus Cordyceps of the family Cordycipitaceae [1]. C. militaris is more and more regarded as a succedaneum for Chinese cordyceps (Ophiocordyceps sinensis) in traditional Chinese medicine on account of similar chemical and medicinal properties [2,3,4].

There are several resemblances between C. militaris and O. sinensis; however, they differ in their hosts, appearance, and geographical distribution. The hosts of C. militaris are Lepidopteran pupae or larvae, and their fruiting bodies are yellow or orange in color (Fig. 7.1a, b), while the hosts of O. sinensis are larvae of Hepialus, and the color of their fruiting bodies is dark brown (Fig. 7.1c, d). The natural resource of Chinese cordyceps fungus is scarce, which is only found on the Tibetan Plateau. Being different from the Chinese cordyceps fungus, C. militaris is distributed worldwide, including North and South America, Europe, and Asia, but with a low population density in nature.

Fig. 7.1
4 photographs of a fruiting body of Cordyceps militaris and Ophiocordyceps sinensis protruding out from the ground in A and C, and from pupae and host in B and D.

Fruiting body of Cordyceps militaris and Ophiocordyceps sinensis in the wild: (a) fruiting body of C. militaris out of the ground; (b) fruiting body of C. militaris and the pupae; (c) fruiting body of O. sinensis out of the ground; (d). fruiting body of O. sinensis and its host

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Cordyceps militaris is well-known because of its radio-protection [5], anti-influenza virus [6], anti-inflammatory, and antitumor [7] activities. A series of components, including cordycepin, adenosine, N6-(2-hydroxyethyl)-adenosine, and carotenoids, have been extracted from the C. militaris. The use of Cordyceps militaris product in medicinal treatment and health products has been well received in several countries, especially in Southeast Asia. In 2009, the Ministry of Health of the People’s Republic of China officially recognized C. militaris as a novel food [http://www.moh.gov.cn/publicfiles/business/htmlfiles/zwgkzt/pgg/200903/39591.htm].

Large-scale fermentation and substrate culture have been widely carried out in China to meet the great demand for medicinal and edible products [8, 9]. At present, the fruiting body has been successfully cultivated commercially, which is not only used in medicine and healthcare products but also can be sold directly in supermarkets as edible fungi.

This review will summarize the research progress including the life cycle and fruiting body cultivation, metabolites and pharmacological activities, pharmaceutical and therapeutic potential, safety and toxicity, as well as industry and applications. The issue of making this prized fungus beneficial to all mankind is critically discussed. This review summarizes the existing research results and lays the foundation for the future research.

2 Life Cycle and Fruiting Body Cultivation

2.1 Life Cycle of Cordyceps militaris

In nature, the complicated life cycle of C. militaris comprises of teleomorph stage and anamorph stage as well as the lifespan of the host insects (Fig. 7.2). The hosts are holometabolous insects (Fig. 7.2). The insects could be infected by conidia, ascospores, and hyphae. Under the specific environmental conditions, the ascospores could be ejected and then diffused by wind or water to infect the insects. C. militaris colonizes the living host insects, and when the insects are eventually dead, it switches to necrotrophy. Being different from the O. sinensis which is homothallic, C. militaris is sexually heterothallic. Interestingly, single mating-type strain could also develop fruiting body without mating and meiosis, but sexual perithecia can’t be generated [10].

Fig. 7.2
An illustration represents the life cycle of Cordyceps militaris, on the left and a holometabolous insect on the right. The lifecycle of Cordyceps militaris includes various stages: ascospore, hypha, conidiogenous structure, conidia, and germination and holometabolous insect includes various stages: egg, larva, pupae, and adult. The conidia and ascospore stage infect the pupae stage of the insect and lead to the development of primordium, fruiting body, and ascus.

Life cycle of Cordyceps militaris

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2.2 The Isolates of Cordyceps militaris

C. militaris can be isolated from spores and tissues. For spore isolation, ascospores ejected from mature stromata are collected and then spread in sterile Potato Dextrose Agar (PDA) medium. The ascospores can germinate after 2–3 days. For isolation of tissue culture, the fruiting body was sterilized with 70% ethanol, and a piece of tissue was cut and put in sterile PDA medium under aseptic conditions.

2.3 Cultivation of Fruiting Bodies of Cordyceps Militaris on Cereal Substrates

Fruiting body cultivation on cereal substrates was divided into six stages: spawn production, mycelial growth under dark, coloring after light irradiation, primordium differentiation, fruiting body development, and fruiting body harvest. In a petri plate, the strain was cultured on Potato Dextrose Agar (PDA), and a sterilizing cutter is used to make five to eight circles with a diameter of 5 mm from the agar plate medium and transfer them to the seed medium, that is, potato dextrose liquid medium. The liquid spawn was cultured in a 500 mL flask with 150 mL of potato dextrose liquid medium in a rotary shaker incubator. Wheat or rice medium was prepared by mixing 30 g of cereal and 45 mL of distilled water in 500 mL glass bottles and was then sterilized. The inoculated cultivation was cultured at 20 °C for 7–10 days under dark condition and then under 12 h light and 12 h dark conditions, with relative humidity greater than 80%. The primordium was induced at temperature of 18–22 °C, high humidity of 70–80% under a light intensity of 400–500 lx. After 60–70 days of culture, fresh fruiting bodies were harvested. The by-products produced in large quantities (mainly culture substrates) are mostly used as animal feed.

2.4 Cultivation of Fruiting Bodies of Cordyceps militaris on Pupae

We can obtain the complete products similar to the natural products of C. militaris by cultivation on pupae. The fruiting bodies of pupae are displayed in Fig. 7.3b; Bombyx mori silkworm pupae can be raised for fruiting body cultivation. In order to remove entangled hyphae, the liquid spawn was prepared as mentioned above and then filtered through sterilized gauze. A syringe is used to inject liquid spawn (0.1 mL) into each pupa. The injected pupae were incubated in containers at 20 °C until fungal growth caused their bodies to become stiff and mummified after injection inoculation.

Fig. 7.3
2 sets of pictorial vertical flow charts represent the cultivation of Cordyceps militaris fruiting bodies. A: Wheat medium in dark is subjected to light irradiation, which leads to the growth of young primordium, primordium, and results in the growth of mature fruiting bodies on wheat medium. B: Seeds lead to sclerotium which leads to the growth of young primordium, primordium, and results in the growth of mature fruiting bodies on pupae.

Cordyceps militaris fruiting bodies cultivated on wheat medium (a) and on pupae (b): D (dark); L (light irradiation for 4 d); ST (sclerotium); YPR (young primordium); PR (primordium); MF (mature fruiting body)

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2.5 Strain Degeneration of Cordyceps militaris and Strain Preservation

During the industrial cultivation, the degeneration of C. militaris strain frequently results in a decline in growth rate, fruiting body output, and secondary metabolite content, which can cause significant financial losses [11, 12]. The degeneration of C. militaris is influenced by environmental factors (such as culture medium, preservation techniques, oxidative stress, and subculture) as well as genetic variation (such as DNA methylation and degeneration-related genes). The primary factor for the degeneration of C. militaris strains is genetic variation [13].

Degradation can be avoided or delayed by proper preservation methods. Lyophilization allows C. militaris strains to preserve their natural properties and avoid degradation, which is appropriate for long-term preservation (at least 4 years). The characteristics of C. militaris strains stored in sterile water are similar to that of −196 °C cryopreservation in liquid nitrogen for at least 1 year. Preservation in sterile water is an effective method for the preservation of C. militaris strains, which can be used in factory production. For this fungus, −80 °C cryogenic freezing is not applicable [14].

3 Metabolites and Biological Activities

Multiple compounds have been extracted, detected, and purified from C. militaris, including cordycepin, cordycepic acid, carotenoids, ergosterol, polysaccharides, nucleosides, and other compounds.

3.1 Nucleosides and Analogues

Cordycepin (3′-deoxyadenosine, C10H13N5O3) is the most important nucleoside analogue which was first purified from C. militaris [15, 16], and it has demonstrated a wide range of pharmacological activities. A ribose moiety is attached to a purine (adenine) nucleoside molecule via a β-N9-glycosidic bond in the structure of cordycepin (Fig. 7.4). Most of the 14C-labeled substances (adenosine, adenine, etc.) and 3H -labeled ribose were determined to be potential cordycepin precursors [17, 18]. Therefore, it was assumed that cordycepin was synthesized via purine nucleotide pathway. However, a comprehensive description of cordycepin production was not proposed and confirmed until 2017 [19]. It was demonstrated that adenosine served as the starting point for the sequential reactions of phosphorylation, dephosphorylation, and reduction, which were performed by the Cns1/Cns2 complex (Fig. 7.4).

Fig. 7.4
A cyclic reaction represents the pathway of cordycepin and pentostatin with a picture of the fruiting body at the center. The molecular structures of C O R and P T N are labeled. The c n s 1 and c n s 2 complex leads to cordycepin which leads to 3 prime-deoxyinosine and the c n s 4 complex leads to pentostatin.

Chemical structures and synthesis pathway of cordycepin and pentostatin [19]: COR, cordycepin; PTN, pentostatin; 3’dI, 3′-deoxyinosine

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Various pharmacological activities of cordycepin including antioxidant, anticancer, anti-inflammatory, antidiabetic, and antimicrobial activities and inhibition of platelet aggregation have been reported (Table 7.1). Cordycepin induces both extrinsic apoptotic and caspase-mediated intrinsic regulation [20,21,22,23], as well as resistant cancer metastasis [22, 24], and proliferation via MAPK [25, 26], GSK-3β [23, 27], and ERK-JNK pathways [26, 28] found that cordycepin may reduce non-alcoholic fatty liver in ob/ob mice, and the potential mechanism may be mediated by reduced expression of genes involved in inflammation and lipid formation. Cordycepin could also modulate the central nervous system by suppressing excitatory synaptic transmission via a presynaptic mechanism in rat hippocampal slices [29]. Besides, cordycepin could shield dopamine neurons from rotenone-induced apoptosis by effectively improving mitochondrial dysfunction [30]. Cordycepin could stimulate Wnt/β-catenin signaling pathway through the activation of adenosine receptors, which may accelerate the process of tissue remodeling, showing its potential in the treatment of skin wounds. In brief, cordycepin showed important therapeutic properties in various ailments, as well as nutraceuticals for chronic disease prevention [31].

Table 7.1 Biological activities of metabolites from Cordyceps militaris
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Another adenosine analogue, pentostatin (2′-deoxycoformycin, C11H16N4O4), was first isolated from Streptomyces antibioticus in the 1970s [32], which is an adenosine deaminase irreversible inhibitor preventing the deamination of cordycepin to 3′-deoxyinosine (Fig. 7.4). It was confirmed that an individual gene cluster can generate both cordycepin and pentostatin [19]. Pentostatin helps to suppress deamination of cordycepin to 3′-deoxyinosine in vivo, probably by blocking adenosine deaminase in C. militaris.

These two adenosine analogues produced in tandem follow a bacterial-like protector-protégé strategy of purine metabolism. Pentostatin, in combination with cordycepin, has been reported in clinical trials of refractory TdT-positive leukemia [http://clinicaltrials.gov/show/NCT00709215].

Pentostatin, a purine analogue, was authorized for use in the United States in 1991 to treat hairy cell leukemia and T cell lymphomas [33]. Pentostatin, as a strong adenosine deaminase (ADA) inhibitor, has also been investigated for use in preventing GVHD (graft-versus-host disease) [34,35,36]. The combination of cordycepin and pentostatin showed reduction of epimastigotes and trypomastigotes in vitro, but no therapeutic effect infected by Trypanosoma cruzi in mice [37]. Pentostatin could also have common adverse effects, including fever, headache, nausea, fatigue, infection, anorexia, vomiting, and rash [33].

Additional nucleosides were isolated from C. militaris such as adenine, adenosine, uracil, uridine, guanidine, guanosine, hypoxanthine, and N6-(2-Hydroxyethyl)-adenosine.

Adenosine (C10H13N5O4, Fig. 7.5) is involved in various physiological and pathophysiological regulatory mechanisms [38] and has been used as quality standard of some cordyceps products. Adenosine serves as a signaling substance in addition to being a significant component of ribonucleic acids and adenine nucleotides. It can regulate energy homeostasis, affect the function of various organs and central nervous system activity, and modulate irregular heartbeat (Table 7.1). Extracellular adenosine acts as a signaling molecule by binding to adenosine receptors, which could trigger multiple signaling pathways to regulate energy homeostasis and affect the operation of many organs [39]. Adenosine can be used for a variety of important therapies, including regulating central nervous system (CNS) function and modulating irregular heartbeat (arrhythmias) [40, 41]. The accumulation of extracellular adenosine in neural tissue resulted in a delay in the synaptic recovery process after spreading depolarization [42]. Leone and Emens described the function of adenosine signaling in regulating tumor immunity, emphasizing underlying therapeutic targets in the pathway [43]. Besides, behavioral and physiological symptoms produced by insufficient adenosine were consistent with many comorbidities of autism in rodents [44], and adenosine might be a novel therapeutic target for autism in rodents and humans [45].

Fig. 7.5
Two molecular structures of adenosine and N superscript 6-, 2-hydroxyethyl, -adenosine.

Chemical structures of adenosine (a) and N6-(2-hydroxyethyl)-adenosine (b) [46]

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The first calcium antagonist of biological origin, N6-(2-hydroxyethyl)-adenosine (C12H17N5O5, HEA, Fig. 7.5), is also an inotropic agent [46]. Among the over 500 species of Cordyceps sensu lato, HEA could be produce by only a few species such as C. pruinosa, C. militaris, and I. tenuipes [47]. Recent studies have shown that HEA has a variety of biological functions. In pharmacological studies, cerebral and coronary circulation could be regulated by HEA which acts as a sedative [48]. It can prevent K562 erythroleukemia cells from proliferating in vitro [49]. The analgesic mechanism of HEA differs from that of opioids, a widely used analgesic drug. More importantly, the benefit of HEA over opioids is that it is neither addictive nor pepsin-affected [50]. Peng et al. reported that HEA shielded mice from renal ischemia reperfusion damage [51]. Additionally, HEA reduced the pro-inflammatory reactions brought on by lipopolysaccharide through inhibiting the toll-like receptor 4-mediated nuclear factor-κB signalling pathway [52]. A recent study showed that HEA targeting an adenosine receptor showed insecticidal activity to Plutella xylostella [53], suggesting an environmentally friendly pesticide [54].

3.2 Polysaccharide

One of the major biologically active elements of C. militaris is polysaccharide. The healthcare and pharmacological activities of C. militaris were confirmed by a mass of animal experiments and clinical experiments (Table 7.1). Cordyceps militaris contains various polysaccharides, which mainly composed of mannose, glucose, and galactose in varying molar ratios [55,56,57,58]. In addition, several isolated polysaccharides contained monosaccharides such as xylose, rhamnose, and arabinose [59, 60]. The change of monosaccharide molar ratio of polysaccharides may be related to raw materials, separation and purification techniques, etc. Polysaccharides had antiviral, antioxidative, anti-inflammatory, antitumor, neuroprotective, antihypertensive, and immunomodulatory biological effects [6, 61, 62]. The biological functions and healthcare functions of polysaccharides were reviewed by Zhang et al. [63].

3.3 Ergosterol

Ergosterol (C28H44O, Fig. 7.6) is an important sterol component of C. militaris which is an indispensable source of fat-soluble vitamin D and can be determined by HPLC method [64]. Ergosterol was first isolated from Claviceps purpurea (Fr.) Tul in 1898; subsequently, it was discovered in a variety of edible and medicinal fungi. As an important component of fungal cell membranes, it plays a significant role in ensuring cell viability, membrane integrity, and completion of the cell cycle.

Fig. 7.6
A molecular structure of ergosterol. It is has fused aromatic rings with methyl, hydroxy and hydrogen functional group.

Chemical structure of ergosterol [64]

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Ergosterol safeguards the phospholipids in cell membranes from oxidation by operating as an antioxidant in a manner akin to vitamin E [65]. Ergosterol significantly improved the anticancer effect [66]. By regulating the TGF-β1/Smad2 signaling pathway, ergosterol decreased the proliferation of mesangial cells and the subsequent deposition of ECM [67]. Both oral administration and intraperitoneal administration of ergosterol inhibited the promotion of bladder carcinogenesis with saccharin sodium, and the last one showed a stronger effect [68].

3.4 Cordycepic Acid

Cordycepic acid (C6H14O6) also known as D-mannitol was first determined from O. sinensis which was reported to be a quinic acid isomer [69]. As a tetrahydroxy monobasic acid, it forms a crystalline tetra-acetate, a mono-methyl ester, and a tetra-benzoate in O. sinensis [69]. The structure and chemical composition of mannitol between O. sinensis and C. militaris are substantially uniform. Cordycepic acid can improve LPS-induced hepatic stem cell inflammation phenotype and TGFB1-induced hepatic stem cell fibrosis response [70]. By regulating Nrf-2/HO-1/NLRP3/NF-κB signal in nude mice, cordycepic acid has a significant antitumor effect on carcinoma of the lung [71].

3.5 Carotenoids

Carotenoids are a class of pigmented chemicals produced by plants and microbes but not by animals [72]. All carotenoids possess a polyisoprenoid structure [73]. Under the illumination condition, the colony of C. militaris exhibited the color of orange with high carotenoid content in mycelia [74]. Carotenoids isolated from the fruiting body of C. militaris include lutein, zeaxanthin, and four cordyxanthins (Fig. 7.7) [75, 76]. C. militaris is rich in carotenoids, with a greater amount than other known mushrooms. It was proposed that carotenoid concentration should be used as a quality criteria for commercial products of this valuable fungus [77].

Fig. 7.7
Four molecular structures of Cordyxanthin-1 and Cordyxanthin-2 are on the top, and Cordyxanthin-3 and Cordyxanthin-4 are at the bottom.

Chemical structure of four cordyxanthins [75]

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As a family of natural organic pigment compounds, carotenoid could decrease oxidative stress, which is related to the progression [78], and the progression of age-related diseases [79]. Cell-mediated immune function and sexual attraction changed with the carotenoid content of the diet in male zebra finches [80]. Carotenoid had also characteristic functions such as cell cycle inhibition, improvement of gap-junctional communication, and induction of cell differentiation and apoptosis [81].

3.6 Other Compounds

5,5’-Dibuthoxy-2,2′-bifuran is initially found from plants. It was extracted for the first time from C. militaris that showed antibacterial activity against Bacillus subtilis and Escherichia coli [82].

In addition to the above compounds, superoxide dismutase (SOD) is an active protease that can eliminate oxidative stress to protect cells from damage of aerobic metabolite [83]. Cephalosporolides C, E, and F, ten-membered macrolides (C10H14O4), 2-carboxymethyl-4-(3′-hydroxybutyl) furan, and pyridine-2, 6-dicarboxylic acid (C7H5NO4) were also extracted from C. militaris [84]. C. militaris lectin showed no hemagglutination activity in human ABO erythrocytes but had agglutination activity in mouse and rat erythrocytes [85]. Cerebrosides with anti-inflammatory and anti-PTP1B activities were isolated in C. militaris [86, 87]. Recently, C. militaris genome mining revealed a possible gene cluster for acyl-CoA: cholesterol acyltransferase inhibitor beauveriolides (Fig. 7.8) [88].

Fig. 7.8
Two molecular structures of beauveriolide-1 on the left and beauveriolide-2 on the right.

Chemical structure of beauveriolides [88]

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Apart from the metabolites described above, genomic analysis of C. militaris identified secondary metabolite clusters of seven polyketide synthases (PKS), five NRPS-PKS, eight non-ribosomal peptide synthetases (NRPS), and four terpene synthases (TS). Many more metabolites should be expected to be dug out.

4 Pharmaceutical and Therapeutic Potential of Cordyceps militaris

Cordyceps has long been used as a tonifying kidney and lung health medicine, as well as to treat asthma, tuberculosis, chronic bronchitis, and other respiratory illnesses. Evidence showed that C. militaris are beneficial to act as anti-angiogenic, anti-inflammatory, antitumor, antioxidant, anti-aging, immunomodulatory, antimicrobial, antiviral, anti-protozoal, insecticidal, anti-fibrotic, hypolipidemic, liver protection, and lung protection. The pharmaceutical and therapeutic potential of C. militaris and the samples used were listed in Table 7.2.

Table 7.2 List of pharmacological effects of Cordyceps militaris
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5 Safety and Toxicity

Mycotoxin contamination in food and feed has long posed a threat to human and animal health [126]. C. militaris has been consumed for many years, and its safety has also been demonstrated because the genome lacks genes known to be responsible for human mycotoxins [127]. The sub-chronic toxicity experiments of submerged mycelial of C. militaris in rats for 90 days showed that the threshold of no adverse reaction of C. militaris hyphae to male and female SD rats was 4000 mg per kg BW per day [128]. C. militaris extract has a good effect on mild liver dysfunction by inhibiting lipid accumulation and slowing down the progression of fatty liver [129]. It was proved that cordycepin is a non-toxic and non-mutagenic compound by test and in rat model. The hematological, blood chemistry, and tissue microanatomical characteristics of rats fed cordycepin daily for 30 consecutive days were not significantly different from those of normal rats [130].

However, the production of highly effective cordycepin and penstatin is a key criterion for the selection of strains for mass production. Similar to the side effects of pentostatin and adenosine analogues, there have been anecdotal reports of the adverse effects of nausea and diarrhea after ingestion of products with high levels of cordycepin/pentostatin [66].

6 Industry and Application

In traditional Chinese medicine, Cordyceps fungi have been employed for centuries. For various biological and pharmacological activities of C. militaris, there are many applications in functional food, healthcare fields, as well as skin care product in China, Japan, Korea, and other East Asian countries. Mass production of C. militaris inoculated on cereal substrates and silkworm pupae has long been successful. Currently, cordyceps have turned to be a big industry. Without taking into account the yield of C. militaris in South Korea, Japan, Vietnam, and Thailand, yearly output amounts to 90, 559 tons in 2018 and annual value of production was about 10 billion RMB in China.

Fruiting bodies have been commercially cultivated on a large scale, not only for medicine and healthcare products but also for direct consumption in supermarkets as edible fungi. There are a great number of products of dry or fresh fruiting bodies of C. militaris on the market (Fig. 7.9). The famous cordyceps recipe is made with duck. C. militaris chicken soup is also popular (Fig. 7.10).

Fig. 7.9
A: 3 photographs, 2 photos of the packed products of fresh fruiting bodies with labels in a foreign language, and a photo of an opened box with fresh fruiting bodies. B: 4 photographs of packed products of dry fruiting bodies, 2 in packets and 2 in bottles with labels in a foreign language.

Fresh and dried fruiting bodies of Cordyceps militaris in the market. (a) products of fresh fruiting body; (b) products of dry fruiting body

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Fig. 7.10
7 photographs of varieties of dishes cooked with Cordyceps militaris. One photo is at the center and the other 6 are arranged around it.

Dishes cooking with Cordyceps militaris

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In 2009, the Ministry of Health of the People’s Republic of China officially recognized C. militaris as a novel food. The fruiting bodies of C. militaris have also been processed into a variety of different products, including cordyceps noodle, drink, tea, and so on (Fig. 7.11). In addition, 36 officially healthy foods are made from C. militaris. Most of them were used for improving the immunity. C. militaris is used in cosmetic, and there are products of mask, lotion, moisturizer, and so on (Fig. 7.12). In recent years, it has been reported that the solid-based residues (SBRs) of Cordyceps mushroom fruiting body can be used as a potential source of crude extracts for cosmetics and can be further used as multifunctional ingredients in cosmetics and cosmeceuticals [131]. Nowadays, an enormous industry building on C. militaris has been flourished in China.

Fig. 7.11
11 photographs of packed noodles, beverages, tea, health food, candy, and health products processed from Cordyceps militaris in A to F. The labels of all the packs are in a foreign language.

Processed foods of Cordyceps militaris. (a) noodle; (b) beverage; (c) tea; (d) health food; (e) candy; (f) health products with high cordycepin content

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Fig. 7.12
3 photographs of a sachet of face masks, bottles with liquid and a spray bottle with lotions are the cosmetic products extracted from Cordyceps militaris.

Cosmetics of Cordyceps militaris

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C. militaris mycelia powder (Z20030034) and capsule (Z20030035) (Fig. 7.13) which are manufactured by Jilin Zhong sheng Pharmaceutical Co., Ltd. have been approved by the Ministry of Health of the People’s Republic of China. The pharmacological effects of the medicines are shown in the drug instruction.

Fig. 7.13
A photograph of a capsule box and 2 cards with text in a foreign language.

Capsule (Z20030035) manufactured by Jilin Zhong sheng Pharmaceutical Co., Ltd., China

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7 Perspective

7.1 Cordyceps militaris and the Other Species of Cordyceps s.l.

Cordyceps s.l. include three families of Hypocrealean fungi, i.e., Cordycipitaceae, Ophiocordycipitaceae, and Clavicipitaceae. Only a few fungi of cordyceps have been employed in traditional medicine, such as Ophiocordyceps sinensis, C. militaris, and C. cicadae (syn. Isaria cicadae). Among them, C. militaris, C. cicadae, and O. guangdongensis have been approved as novel foods by the Ministry of Health of the People’s Republic of China. All the related fungi were called as Cordyceps fungi. Here, we called on that the accurate species name should be used both in the scientific research and industrial production in case of confusion.

7.2 In-Depth Investigations of the Secondary Metabolites of Cordyceps militaris

Except cordycepin, the polysaccharides of other pharmacologically active compounds need to be identified and elucidated in relation to their structure and function. In contrast to the few known metabolites, C. militaris genome encodes a series of biosynthetic gene clusters with the potential to generate a large number of unknown compounds. Full elucidation of the production capacities of different secondary metabolites is an urgent need in the future.

7.3 Quality Control for Cordyceps militaris Products

Although C. militaris has become a massive industry and various products have been in market, there are no special active components for the products except the common ones such as polysaccharides and adenosine. One of the major problems limiting development in modern industry is the lack of quality control over medicinal fungi and other traditional Chinese medicines. Chemical (secondary metabolites) and protein fingerprinting should be the choice for the quality control in industry.

8 Conclusions

Cordyceps militaris has attracted considerable research and commercial interest because it contains active compounds beneficial to human health, and the fruiting bodies are relatively easy to grow with a short growth period. We believe the fruiting body and the products of C. militaris will benefit mankind more and more in the future.