The Pharmaceutical Benefits of Cordyceps
The Pharmaceutical Benefits of Cordyceps
The Pharmaceutical Benefits of Cordyceps
Review:
The endless nutritional and pharmaceutical benefits of the Himalayan
gold, Cordyceps; Current knowledge and prospective potentials
Abstract. Elkhateeb WA, Daba GM. 2020. Review: The endless nutritional and pharmaceutical benefits of the Himalayan gold,
Cordyceps; Current knowledge and prospective potentials. Biofarmasi J Nat Prod Biochem 18: 70-77. As a traditional medicine,
Cordyceps has long been used in Asian nations for maintaining vivacity and boosting immunity. Numerous publications on various
bioactivities of Cordyceps have been investigated in both in-vitro as well as in vivo studies. Nevertheless, the role of Cordyceps is still
arguable whether it acts as food supplement for health benefits or a real healing drug that can be prescribed in medicine. The Cordyceps
industry has developed greatly and offers thousands of products, commonly available in a global marketplace. In this review, focus will
be on introducing the ecology of Cordyceps and their classification. Moreover, elucidation of the richness of extracts originated from
this mushroom in nutritional components was presented, with description of the chemical compounds of Cordyceps and its well-known
compounds such as cordycepin, and cordycepic acid. Furthermore, highlights on natural growth and artificial cultivation of famous
Cordyceps species were presented. The health benefits and reported bioactivities of Cordyceps species as promising antimicrobial,
anticancer, hypocholesterolemic, antioxidant, antiviral, anti-inflammatory, organ protective agent, and enhancer for organ function were
presented.
Partial Clavicipitaceae
Drechmeria 2
Hypocrella 50
Metacordyceps 4
Metarhizium 35
Nomuraea 3
Pochonia 3
Podocrella 4
Figure 1. Cordyceps sinensis (Collector: Soraj25: Locality:
Regiocrella 2
Nepal, Mid-Western, Jumla, Nepal, hosted by
Sphaerocordyceps 2
http://mycoportal.org)
Tyrannicordyceps 5
Total: 10 110
Ophiocordycipitaceae
Blistum 1
Didymobotryopsis 3
Elaphocordyceps 1
Haptocillium 8
Hirsutella 78
Hymenostilbe 22
Ophiocordyceps 155
Paraisaria 2
Perennicordyceps 4
Polycephalomyces 12
Purpureocillium 3
Syngliocladium 5
Synnematium 1
Tolypocladium 39
Trichosterigma 1
Total: 15 335
Figure 2. Cordyceps militaris (Collector: Marjan Kustera:
Cordycipitaceae Locality: Gabrovac, Serbia, hosted by http://mycoportal.org).
Akanthomyces 13
Ascopolyporus 7
Beauveria 31 Classification of the genus Cordyceps was previously
Beejasamuha 1
within family Clavicipitaceae, order Hypocreales (the old
Cordyceps 175
Coremiopsis 2 genus Cordyceps Fr.). Currently, many genera have
Engyodontium 5 segregated from the genus Cordyceps such as
Gibellula 21 Metacordyceps, Tyrannycordyceps (placed in family
Hyperdermium 2 Clavicipitaceae); Elphcordyceps, Ophiocordyceps (in
Insecticola 2 family Ophiocordycepitaceae); Sphaerocordyceps, and
Isaria 83 remaining Cordyceps species (placed in Incertae sedis
Lecanicillium 21 within Hypocreales). Due to their special nutritional and
Microhilum 1 healing values, Cordyceps is widely spreading in China,
Phytocordyceps 1
with a huge existing domestic market. In Chinese market,
Pseudogibellula 1
Rotiferophthora 27 Cordyceps is known as ‘Dongchong Xiacao (worm in
Simplicillium 8 winter, herb in summer; O. sinensis (Berk.) Sung et al.
Torrubiella 66 2007) which is the most expensive type and only produced
Total: 18 467 from the Tibetan Plateau; other Cordyceps species in the
markets are termed ‘fake Dongchong Xiacao’.
Total: 3 families, 43 genera and 912 species
Note: The data is counted from Catalogue of Life:
http://www.catalogueoflife.org/, access in June 2017)
72 B I OF A R MA S I J NA T P R O D B IOCH E M 18 (2): 70-77, August 2020
trials using various organic substrates by Yue et al. (1982). Anticancer activities of Cordyceps
For commercial production of C. militaris stromata, cereals Various Cordyceps originated bioactive compounds
including rice have been widely used (Wen et al. 2008; having promising anticancer activity that were previously
Chen et al. 2011). Also, using substrates such as wheat reported (El-Hagrassi et al. 2020). For example, cordycepin
grains, cottonseed coats, corn cobs, corn grain, bean showed antitumor activity against B16 melanoma cells
powder, millet, and sorghum have shown promising results (Yoshikawa 2004 and 2007). In addition, cordycepin
(Chen and Wu 1990; Zhang and Liu 1997; Gao and Wang inhibited the mammalian target of rapamycin complex 1 in
2008, Wei and Huang 2009). The optimum organic gallbladder cancer cells in-vitro resulting in loss of cancer
substrate currently used is a mixture of rice and silkworm cell viability and apoptosis (Wong et al. 2010; Ferreira et
pupae (Shrestha et al. 2005, Sung et al. 2006; Jin et al. al. 2010; Wu et al. 2014). C. militaris was found to inhibit
2009). Furthermore, brown rice, malt, and soybean were U937 cells growth in a dose-dependent manner and limit
found to be important sources of nutrition for C. militaris human leukemia (Park 2005). Cordyceps has shown
in comparison with chemical media (Xie et al. 2009). C. promising results in slowing and inhibiting the growth of
militaris cultivation needs a relatively low level of nitrogen cancer cells (Santhosh Kumar et al. 2014) and in some
(Gao et al. 2000) which may explain lower yields when cases could reduce tumor size (Nakamura et al. 2003).
using insects in comparison with higher yields reached Clinical trials on cancer patients have been conducted in
when cereals were used in the culture. Plant hormones such many Asian countries, showing talented results in reducing
as colchicines, 2, 4-D, citric acid triamine can promote C. tumor size (Wang et al. 2001), improving tolerance for
militaris stroma production. Also, potassium, calcium, and chemotherapy and/or radiation (Zhou et al. 1998) and in
magnesium salts can increase the yield of fruiting bodies stimulating the immune system which, hence, enhances the
(Xiao et al. 2010). efficiency of chemotherapy (Shin et al. 2003). Crude
Mycelia production for the aim of large scale extract of C. militaris showed potent anticancer activity in
production of bioactive compounds is also achievable and a xenograft mouse model with RMA cell-derived tumors
has been performed in submerged culture (Huang et al. (Park et al. 2017). Additionally, some Cordyceps species
2006; Xie et al. 2009; Das et al. 2010). C. militaris have anti-leukemia activities and better suppressive effects
cultivation has been improved, which results in successful of chemotherapy on bone marrow function as a model for
production of high yield of stromata and elevated cancer treatment (Liu et al. 2008; Wong et al. 2010;
cordycepin content (Sun et al. 2009; Du et al. 2010). Ferreira et al. 2010).
Production of fruiting bodies has been studied for three
successive generations (Hong et al. 2010; Xiao et al. 2010; Hypoglycemic and hypocholesterolemic effect
Shrestha et al. 2012; Xiaoli et al. 2014). Cordyceps are found to regulate and also lower the
blood sugar levels by improving metabolism of glucose and
conserving hepatic glycogen (Zhao et al. 2002; El-Hagrassi
CORDYCEPS AND HEALTH BENEFITS et al. 2020). Cordyceps can increase secretion of
glucokinase and hexokinase which are glucose regulating
The genus Cordyceps species are extensively studied enzymes secreted by the liver (Kim et al. 2017).
due to the uncountable number of medical-biological Polysaccharides are the key player in showing the
activities used by their extracted compounds, with various hypoglycaemic activity of Cordyceps. For example, CS-
medical and nutritional values. In traditional Chinese F30, a polysaccharide extracted from C. sinensis culture
medicine, the main use of Cordyceps has been in the mycelium has been reported for its promising
treatment of asthma and other bronchial conditions, and hypoglycaemic effect (Kiho 1996). Additionally, the
giving energy and sexual power. Recent research now plasma glucose level was reduced quickly after intravenous
confirms the competence of Cordyceps in many other administration of CS-F30 in normal and streptozocin-
fields. One of the advances of modern research has been induced diabetic mice (Kiho 1996). Another
the discovery of cordycepin, which has a potent polysaccharide (CS-F10), was purified from a hot-water
antibacterial action against majority of bacterial species extract of C. sinensis cultured mycelia and consists of
that have currently developed resistance to other commonly galactose, glucose, and mannose in a molar ratio of
used antibiotics. Cordyceps showed remarkable activity 43:33:24. CS-F10 lowers the plasma glucose level in
during treating tuberculosis and human leukemia, as shown normal, adrenaline-induced hyperglycaemic and diabetic
in many clinical trials in Asia and elsewhere (Halpern mice. Hypercholesterolemia is an indicator for high risk of
Georges 2007). Cordyceps was shown to improve the cardiovascular attack. El-Hagrassi et al. (2020) reported the
maximum amount of oxygen and to improve respiratory role of C. militaris in lowering the total cholesterol level
function. Other components produced by Cordyceps and the level of triglycerides. A hot-water extract of C.
sinensis include the deoxynucleoside 2', 3' deoxyadenosine. sinensis mycelia has been found to reduce total cholesterol
Also, Quinic acid derived from cordycepin obtained from concentration in the serum of mice, by reducing LDL(low-
Cordyceps, exerts antimicrobial and antiviral activities. density lipoprotein) hypocholesterolemic activities (El-
Many studies have reported the potency of Cordyceps Hagrassi et al. 2020). A hot-water extract of C. sinensis
sinensis in healing heart rhythm disturbances such as mycelia has been found to reduce total cholesterol
chronic heart failure and cardiac arrhythmia (Mishra and concentration in the serum of mice, by reducing LDL) and
Yogesh 2011; Wang et al. 2012).
74 B I OF A R MA S I J NA T P R O D B IOCH E M 18 (2): 70-77, August 2020
very-low-density lipoprotein, and increasing good cooling effects. On the respiratory system, C. sinensis has a
cholesterol concentration (HDL cholesterol) (Koh 2003). potent relaxant action on bronchi, noticeably increases
secretion of adrenaline from the adrenal glands, and also
Improving kidney functions and liver disorders participates in tracheal contraction caused by histamine; it
Some clinical trials revealed that the administration of additionally has an expectorant, antitussive, and anti-
C. sinensis could significantly improve kidney function and asthmatic effects, and it also inhibits pulmonary
boost overall immunity of patients diagnosed with chronic emphysema. On the endocrine system, C. sinensis has
renal failure (Guan et al. 1992). Additionally treating effects as a male hormone. Polysaccharides extracted from
patients with gentamicin-induced kidney damage helped in Cordyceps can increase corticosterone levels in plasma.
recovering 89% of normal kidney function in a relatively Cordyceps is used in traditional medicine for decades to
short time (Zhou et al. 1990). The mode of kidney improve men's fertility. A study has proven the positive
enhancing action of Cordyceps is explained by its ability to effect of using C. militaris mycelium on sperm motility,
protect sodium pump activity of tubular cells, increase 17- morphology, productivity, and enhancement of sexual
ketosteroid and 17-hydroxycorticosteroid levels in the activity (Lin et al. 2007). Cordyceps extracts contain
human body, reduce content of calcium in certain tissues, adenosine, deoxyadenosine, related adenosine type
and accelerate regeneration of tubular cells (Zhou et al. nucleotides, and nucleosides which help in stabilizing
1990; Xu et al. 1995; Wang et al. 1998). Cordyceps is heartbeat and correcting heart arrhythmias (Pelleg and
commonly used for the treatment of chronic hepatitis B and Porter 1990).
C. Using the antiviral drug, lamivudine, plus mixed
extracts of Cordyceps with other medicinal mushrooms Cordyceps as anti-inflammatory
showed promising results for treating hepatitis B (Wang Commonly, the famous cordycepin is the compound
and Shiao 2000; Ng and Wang 2005; Zhou et al. 2009). On causing the anti-inflammatory activity of numerous
the other hand, daily consumption of Cordyceps improved Cordyceps species (Won and Park 2005; Kim et al. 2006;
liver functions in patients suffering from post-hepatic Yang et al. 2011). C. militaris ethanolic extracts of cultured
cirrhosis (Zhu and Liu 1992; Zhou et al. 2009). Cordyceps fruiting bodies and mycelia exerted an anti-inflammatory
extracts is used to help in the healing of both chronic activity on the chick embryo chorioallantoic membrane
hepatitis B and C (Wang and Shiao 2000). angiogenesis, and in the croton oil-induced ear edema in
mice (Won and Park 2005). On the other hand, an alkaline
Cordyceps as antioxidant and antiaging activities extract of C. militaris, showed a strong anti-inflammatory
One of the most potent bioactivities reported for effect against formalin-induced nociception and LPS-
Cordyceps extracts is their ability to protect cells from induced peritonitis in mice, due to containing a potent anti-
being damaged by free radicals. This activity is inflammatory compound (linear b- (1R3)-D-glucan)
corresponding to polysaccharide fraction (Yu et al. 2007; (Smiderle et al. 2014; Park et al. 2015). Adenosine is also
Wang et al. 2012). Cordyceps sinensis has potent extracted from Cordyceps species with numerous activities
antioxidant and anti-aging properties (Yamaguchi et al. related to avoiding tissue damage as anti-inflammatory
2000; Ji et al. 2009). Also, many studies elucidated the properties (Nakav et al. 2008; Tsai et al. 2010; Liu et al.
antioxidant effect of extracts obtained from C. militaris 2015).
(El-Hagrassi et al. 2020). The fruiting bodies extract of C.
militaris showed strong DPPH radical scavenging activity, Cordyceps as antiviral agents
which indicated high antioxidant activity, while the Many studies reported that cordycepin extracted from
fermented mycelia extract had stronger total antioxidant C. militaris can inhibit infection with human
activity, and reducing capability (Dong et al. 2014). immunodeficiency virus (Mueller et al. 1991). Cordycepin
Cordyceps has been used for centuries as a remedy for has shown antiviral activities against different viruses such
weakness and fatigue by residents living in the high as plant viruses, and human viruses (influenza virus,
mountains of Tibet to give them energy which is achieved Epstein-Barr virus, murine leukemia virus) (Ryu et al.
by increasing cellular ATP (Holliday et al. 2008). 2014). Till now, the mode of killing or inhibiting actions of
Nowadays, Cordyceps is utilized by athletes to overcome cordycepin is not fully understood, but number of studies
weakness and fatigue, and to increase endurance and boost have elucidated the ability of cordycepin to inhibit
energy levels (Liu et al. 1997). Moreover, clinical trials numerous protein kinases (Glazer and Kuo 1977; Jin et al.
connecting chronic fatigue with aging patients revealed that 2011; Elkhateeb et al. 2019). On the other hand crude
treatment with C. sinensis resulted in improvement of extract of fruiting bodies of C. militaris showed promising
fatigue and dizziness, increasing cold intolerance, and in-vitro antirotavirus SA-11 agents activities (El-Hagrassi
amnesia (Mizuno, et al. 1999; Chen et al. 2013; Wu et al. at al. 2020).
2014).
Cordyceps side effects and safety
Cordyceps for organs and glands protection Cordyceps is generally safe in recommended dosage
Cordyceps sinensis also has clear effects on other organ and no major side effects were reported. (Das et al. 2010).
systems (Chen 1995; Zhang and Yuan 1997; Guo and Guo
2000; Xu 2006). For example, in the central nervous
system, C. sinensis has sedative, anticonvulsant and
ELKHATEEB et al. – The endless story of the Himalayan gold Cordyceps 75
CONCLUDING REMARK Elkhateeb WA, Daba, GM, Thomas PW, Wen TC. 2019. Medicinal
mushrooms as a new source of natural therapeutic bioactive
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