Cordyceps Polysaccharides

Cordyceps Reishi


Cordyceps, parasitic fungi grown on the larva of caterpillar, is a unique and precious edible and medicinal herb in Traditional Chinese Medicine (TCM), and has long been used in traditional therapies. Polysaccharide, one of the bioactive constitutents of Cordyceps, exhibits a wide range of bioactivities. In recent years, with the development of agamotype and submerged fermentation technologies of Cordyceps, production reached an increased level. Meanwhile, research on Cordyceps polysaccharide attracted increasing attention because of its multi-pharmacological functions such as immunomodulation, anti-tumor, antioxidant, hypoglycemic, renal and liver protective effects, etc. This chapter will provide detailed information on the extraction, purification, chemical composition, chain conformation and pharmacologic function of polysaccharides from various Cordyceps species, especially Cordyceps sinensis (Berk.) Sacc. and Cordyceps militaris (Fr.) L.

d General comments

The unworkably complex traditional taxonomy of Cordyceps (Kobayasi, 1941, 1982) led to species identifications based more often on magnificent watercolored illustrations (Kobayasi & Shimizu, 1983) or photographs (Sung, 1996) than on taxonomic descriptions. The phylogenetic reclassification of fungi has transfigured Cordyceps: two new families were segregated from the Clavicipitaceae, and hundreds of Cordyceps species reassigned among four genera and in each of these families (Sung et al., 2007). Cordyceps (sensu stricto) includes species with pale to brightly colored fleshy (soft) stromata, perithecia on or immersed in (and perpendicular to the surface of) the stroma or subiculum. Metacordyceps species form fibrous to tough stromata with a stipe expanding into a cylindrical or clavate apical fertile part, pale to yellow–green or greenish or purplish, and hosts that are usually buried in soil. Few Elaphomyces species attack insects (cicada nymphs or other subterranean insects), and these form fibrous, pale to brownish stromata with a fertile (apical) knob or (lateral and subapical) pads or cushions containing perithecia. Ophiocordyceps species usually form darkly pigmented stromata arising from hosts buried in soil or decaying wood, stromata may be wiry to clavate/fibrous, and most perithecia occur on the stromatic surface or in patches or lateral pads below the tip of the stroma. Among the genera into which Cordyceps (sensu lato) was split, Ophiocordyceps now includes the most species followed by Cordyceps in its newly restricted

Torrubiella Boud., Clavicipitales

This genus is separated from Cordyceps by the absence of erect stromata, the perithecia being borne directly on or around the host. Of the 54 species recorded (Kobayasi and Shimizu, 1982), most are confined to either spiders or Homoptera. Kobayasi and Shimizu (1982) noted twelve species on ‘scale insects’. There is only one reliable record from Coccidae – T. confragosa Mains as a pathogen of Saissetia sp. (Evans and Samson, 1982). This species was described by Mains (1949) from ‘large scale-insects’ (Coccidae) in Brazil. Evans and Samson (1982) were also able to link this teleomorph with an anamorph – Verticillium lecanii (Zimm.) Viégas. Verticillium lecanii is commonly recorded on a range of Homopteran insects and has been widely reported from Coccidae (Table 2.1.1). Torrubiella lecanii Johnston was described by Johnston (1918) on soft scales (Saissetia hemisphaerica) from Cuba in association with V. lecanii, but the type has apparently been lost and this record cannot be confirmed. Moreover, the illustration is not typical of T. confragosa but is similar to that of T. sphaerospora Samson, van Reenen and Evans, reported from “Coccidae” in Ghana (Samson et al., 1989).

Jinshuibao Capsule

Jinshuibao Capsule (Golden Water Treasure Capsule), made from cultured Cordyceps mycelia, is widely used in China for improving kidney function in patients with chronic kidney disease. Although it is believed to be as safe in clinical practice as wild Cordyceps, a precious Chinese medicine, it has been reported to cause adverse skin reactions [168].

A 27-year-old man with nephritis developed recurrent edema of the face and both legs. He was given oral Jinshuibao three capsules tds, in combination with prednisone and dipyridamole. About 10 hours after the first dose, he developed erythema with severe itching in the chest, back, and limbs, and sporadic rashes. He reported having used oral dipyridamole without a similar experience. The Jinshuibao was then stopped, and he was given oral chlorphenamine and intravenous dexamethasone 5 mg. The erythema and rash gradually diminished over 2 days.

2.3.3 Fungi

As mentioned above, because of their unusual and very visible appearance, fungal infections by Cordyceps were observed in silkworms in the early Chinese silk industry. The first published record of Cordyceps was a report of “vegetable growths” by the French scientist René-Antoine Ferchault de Réamur (1683–1757) (Réamur, 1734–1742). Hagen (1879) observed an epizootic of fungi in a dung fly that occurred in 1867. Cohn (1855) described a fungus that he named Empusa on the house fly, but there was debate over the name because Empusa is also a genus of orchid. The German physician J. B. Georg W. Fresenius (1808–1866) proposed the name Entomophthora (Fresenius, 1856). The Russian scientist Eli Metchnikoff (beginning in 1878) found a fungus, which he called green muscardine (Entomophthora anisopliae), on the wheat cockchafer, a serious pest in Russia (Metchnikoff, 1879) (later named Metarrhizium anisopliae by Sorokin (1883) and now spelled Metarhizium). Metchnikoff found that larvae could be infected by being placed in soil contaminated with conidia. He cultured the fungus on artificial medium consisting of sterilized beer mash, and put forth some of the earliest proposals to use a pathogen for the control of insects (Steinhaus, 1975). Several other European scientists suggested the use of fungi against flies, the nun moth (Lymantria monacha), grasshoppers, and others (Tanada and Kaya, 1993). The first fungal infection of an aquatic insect, Coelomomyces in mosquito larvae, was described by Keilin (1921).


β-d-glucan is a major type of bioactive polysaccharide commonly found in edible fungi, especially LentinusCordyceps, and Ganoderma, which are among the most popular and treasured edible and medicinal fungi since ancient times in China. The β-glucans isolated from LentinusCordyceps, and Ganoderma were a kind of homopolysaccharide with backbones of β-(1 → 3)-linked, β-(1 → 6)-linked, and/or β-(1 → 4)-linked d-glucan, and the branching point located at O-6, O-3, or O-4 position. Among them, a characteristic structure of linear β-(1 → 3)-d-glucan with (1 → 6)-β-d-Glcp side chains is frequently reported. For example, lentinan from Lentinus edodes (yield 5%, w/w) has been applied in adjuvant therapy for cancer diseases through the enhancement of immune system. In particular, β-(1 → 3)-glucan with triple helical chain conformation was most effective. Other kinds of chemical structures, including β-(1 → 6)-d-glucan, β-(1 → 4)-d-glucan, as well as a mixed β-(1 → 3)(1 → 4)(1 → 6)-backboned d-glucan, were also reported. This chapter aims to summarize the advances in research of β-glucans derived from LentinusCordyceps, and Ganoderma species, focusing on their isolation methods, purification processes, detailed structures, and chain conformation. Besides, a range of functional activities are comprehensively reviewed, including immunomodulatory, antitumor, anticancer, antivirus, antioxidant activities, etc. Potential for further developments and applications is also briefly discussed.

4.56.3 Conclusions

Many animal- and plant-based food delicacies such as Kopi Luwak coffee, birds’ nests, Argan oil, cordyceps, some cheeses, and honey are the result of unique and sometimes quirky animal or plant bio-processing, each providing its own unique signature effect. To understand bio-processed food delicacies, food scientists must use a wide variety of information from different sources in order to understand how the original raw food was bio-processed. Information includes animal/plant physiology and biochemistry, environmental aspects (e.g., food sources, growing/living conditions, and migration patterns), cultural significance, ecological role, etc. Likewise, physical and chemical information is obtained from a variety of laboratory tests and investigative tools. All information regardless of its source provides clues which, when put together, provide a comprehensive ‘picture’ of the delicacy being investigated.

Such a comprehensive approach is required not only to characterize and document genuine food delicacies, but also to authenticate genuine food delicacies. Unfortunately, they are also needed to detect food delicacies that have deliberately been altered (adulterated) with the use of a variety of techniques and raw ingredients, often producing fakes which cannot be identified by mere visual inspection. Being able to detect these adulterated food delicacies quickly and reliably is imperative to protect the animal/plant source, the integrity of the genuine product, genuine producers, and ultimately the consumers. And that is advantageous to all!


Cordyceps is regarded in Traditional Chinese Medicine as a premier “kidney tonic” that may prevent gentamicin-induced nephrotoxicity in animals. Cordyceps ameliorated deterioration of tubule metabolism and ion transport (Tian, 1991a), promoted DNA synthesis of kidney cells, lessened urinary β-N-acetylglucosaminidase and lysozyme levels, and delayed proteinuria (Tian, 1991b, 1991c). A comparative clinical study of Cordyceps (3-5 g/day) was conducted in 51 patients with chronic renal failure. In all, 28 received Cordyceps and showed a significant increase in renal function and T-lymphocyte subsets, including the T helper cell ratio, compared with the control group (Guan, 1992).

Cordyceps spp.

Cordyceps species are an entomopathogenic fungi widely used in traditional Chinese medicine. Das et al. (2010) reported that different constituents from Cordyceps species possessed antioxidant/antiaging, antimicrobial, immunomodulatory, antiinflammatory, and antitumor effects. Cordycepin as the major constituent of C. militaris, detected from fruiting bodies, is actually a derivative of the nucleoside adenosine (Fig. 5.4). These days this molecule could be produced industrially because of its antibacterial, insecticidal, and antitumor activities. Among other products isolated from C. militaris are polysaccharides and ergosterol with a number of biological effects: antioxidant, antiinflammatory, antimetastatic, antitumor, immunomodulatory, steroidogenic, hypoglycaemic, and hypolipidaemic. Polysaccharides extracted from fruiting bodies of C. militaris showed immunostimulating properties and stopped growth of melanoma cells tested in vivo on mouse model (Lee and Hong, 2011). Rao et al. (2010) also proved that different extracts and compounds of C. militaris possessed antiinflammatory, antiproliferative, and antiangiogenic activity. Polysaccharidic extracts are responsible for the in vitro antioxidant capacity of C. militaris (Chen et al., 2013; Wang et al., 2012a,b).

Another bioactive compound from C. militaris is cordymin. This peptide was studied for its antifungal properties, and found to inhibit mycelial growth of Bipolaris maydisMycosphaerella arachidicolaRhizoctonia solani and Candida albicans. Cordymin also displayed antiproliferative activity toward breast cancer cells (MCF-7) (Wang et al., 2012a,b). Mannitol and trehalose were found in C. militaris by Reis et al. (2013). These compounds showed good diuretic, free-radical activities and antitussive effects (Das et al., 2010). Citric acid was detected in higher percentage (Reis et al., 2013) in this mushroom. This compound plays an important role in human metabolism especially for structure of bones (Hu et al., 2010). p-Hydroxybenzoic acid was the only phenolic acid compound presented in the extract of C. militaris (Reis et al., 2013). Hydroxybenzoic and hydroxycinnamic acids are the basic structure of phenolic acids. These compounds exhibited antioxidant activity because of their possibilities to be good free radical scavengers, on peroxyl and hydroxyl radicals, peroxynitrites, and superoxide anions (Carocho and Ferreira, 2013). Stearic acid, palmitic acid, linoleic acid, and oleic acid were detected as major fatty acids in this species. Polyunsaturated fatty acids were dominant with 68.87%, whereas saturated fatty acids were presented with 23.40%, and 7.73% was monounsaturated fatty acids (linoleic acid 68.00%) (Reis et al., 2013). The importance of unsaturated fatty acids is that they could protect against cardiovascular disease and decrease blood lipids. Moreover C. militaris is a great source of nonfat compounds. Reis et al. (2013) found that δ-tocopherol is the only form of tocopherols isolated from this species. This work represents the first result considering to organic and phenolic acids, and vitamin E isolated from C. militaris. Authors showed that this extract possessed a number of biological activities: reducing power inhibition, lipid peroxidation inhibition, scavenges free radicals, and high antimicrobial effects. Extract of C. militaris showed much better antibacterial activity than commercial antibiotics, and antifungal activity was better than mycotics against Penicillium ochrochloronP. funiculosum, and Trichoderma viride. This study proved that extracts of C. militaris could be used as a good alternative to synthetic antimicrobial agents in prevention and treatment of different plant, animal, human pathogenic species, and food-borne pathogens. It could be applied as a good preservative in food production and in mushroom and plant cultivation. Methanolic extract of C. militaris tested in previous studies exhibited an inhibitory effect on cell growth against a few human tumor cell lines, but did not affect tumor porcine liver primary cells. Methanolic extracts of C. militaris, mycelia, and fruiting body also confirmed this effect in other human tumor cell lines (Liu et al., 2014; Reis et al., 2013). Cordycepin isolated from Cmilitaris inhibited growth of human leukemia cell by inducing apoptosis (Jeong et al., 2011). Authors concluded that this effect is probably due to the generation of reactive oxygen species, activation of caspases, mitochondrial dysfunction, and cleavage of poly(ADP-ribose) polymerase protein. Apoptosis of human leukemia cells induced by cordycepin is caused by a cascade involving an ROS-mediated caspase pathway. Two acidic polysaccharide fractions, were extracted in fruiting bodies of C. militaris, cultivated one, and evaluated for proliferation of mouse splenocyte activity in vitro (Wu et al., 2012). Both fractions possessed dose-dependent mitogenic effects on mouse splenocytes, and could synergistically promote murine T- and B-lymphocytes induced by Con A and LPS. These results are valauble for the explanation of the connection between polysaccharide structures and their biological activities. Bizarro et al. (2015) tested the mechanism of action of C. militaris methanolic extract on lung cancer cell line (NCI-H460). The extract decreased cellular proliferation, induced cell cycle arrest at G0/G1, and increased apoptosis, and increased the levels of p53 and p21. An increase in p-H2A.X and 53BP1 levels, the number of 53BP1 foci/cell (all indicative of DNA damage), were also observed after treatment with the extract. This extract affected NCI-H460 cellular viability through a mechanism involving DNA damage and p53 activation, which supports the using use of extract as a source of bioactive compounds, which may be used in anticancer strategies.


The family Clavicipitaceae (Hypocreales and Ascomycota) includes saprotrophic and symbiotic species associated with insects and fungi (Cordyceps spp.) or grasses, rushes, and sedges (Balansia spp., Epichloë spp., and Claviceps spp.). In a phylogenetic context, the Clavicipitaceae has been considered to be a monophyletic group derived from within the Hypocreales. The most primitive and widespread members of the family are soil saprophytes and insect pathogens. The soil-inhabiting genera are deeply rooted in phylogenetic trees based on gene sequences (Figure 1), suggesting that they are the most primitive members of the family. These are often identified as species of the teleomorphic genus Cordyceps. Frequently Clavicipitaceae found in soil are known only in their anamorphic states. These include several hyphomycetous soil genera (e.g., AcremoniumChaunopycnisPaecilomycesMetarhiziumLecanicilliumBeauveria, and Hirsutella).The family Clavicipitaceae is distinguished by its wide host range and diverse ecologies. To explain the evolutionary history of the family, it has been proposed that interkingdom host jumps occurred among the animal, fungal, and plant hosts species. Recent studies based on multigene phylogenetic analysis and ancestral character state reconstructions have further shown that the grass endophytes were derived from insect parasitic species through a process of successive host jumping.