Recent discovery:

Medicinal Mycology A Cordyceps species that

Robert Dale Rogers genus of Ascomycetes, known to be
entomopathogenic (insect killing) fungi.
“is relatively easy to propagate
organically, leading to new
scientific findings of health
benefits and increased
consumer demand for the
fruiting body medicine.”
chong xia cao (“winter worm, summer
grass”) it is one of the most valuable

Y
artsa gunbu is the common name
for Cordyceps (Ophiocordyceps
sinensis [Berk] G. H. Sung,
Hywei-Jones & Spatafora) growing in
the mountains of Tibet and elsewhere
in China, and Nepal. Cordyceps is a
Its medicinal use was first recorded in
the 15th century Tibetan text An Ocean of
Aphrodisiacal Qualities. The fungi attack
one of several species of underground
ghost moth larvae (Thitarodes/Hepialus)
as part of their life cycle. Known as dong
medicinal mushrooms in the world. But
it appears the “Himalayan Viagra” gold
rush may be coming to an end. Climate
change and over-harvesting are part of
an unsustainable future.
Between 2001 and 2012, the

Cordyceps militaris
grown in culture.
Photo by Mike Withrow.

42 FUNGI Volume 10:1 Spring 2017


Constituents of Cordyceps
militaris fruiting bodies
Fruiting bodies contain cordycepin
(2’deoxyadenosine), adenosine
(33-37%) beta-D-glucans,
saccharides, nucleosides, mannitol,
sterols, cerebrosides including
cordycerebroside A, soyacerebroside I,
and glucocerebroside.
Cultivated fruiting bodies may also
contain trehalose, 6-hydroxy ethyl
adenosine, nicotinic amide, butyric
acid, beta-dimorphecolic acid, alpha-
dimorphecolic acid, palmitic acid,
linoleic acid, cordycepeptide A,
4-(2-hydroxy-3((9E,12E)-octadeca-
9-12-dinoyloxy)propoxy)-2-
(trimethylammonio)butanoate,
4-(2-hydroxy-3(palmitoyloxy)
propoxy0-2-(trimethylammonio-
butanoate, linoleic acid methyl ester.
temperature above 10,000 feet has
increased by an entire degree Fahrenheit.
The annual harvest is still 135 tons,
but the number of pickers has declined
in past few years. After prices topped
$50,000 per pound in some coastal
cities of China, things have cooled
considerably. At one time, harvesters
were earning an average of US$2,500
or 56% of their annual income from
selling the fungus. Daniel Winkler,
noted ethnomycologist and expert
on Tibetan Cordyceps, elaborates,
“Many big Chinese universities have
sent researchers, but they just want
to know how to cultivate it artificially,
to grow it in a lab. They completely
ignore what it means for the Tibetan
people.” He estimates that over one
million Tibetans pick, sell or trade the
fungus. The Tibetan mushroom has
been, however, resistant to commercial
production of fruiting bodies. Today,
much of the Cordyceps product on the
market is mycelium originating from
strains of an anamorph known as CS-4
which has 99.6% similarity in rDNA
sequence to O. sinensis.
This product is widely produced in
North America and Asia and is the most
common “Cordyceps” found on health
food store shelves. The presence of
cordycepin depends upon the method by
which mycelium is grown and harvested.
Product using liquid culture or
fermentation, grown in China, contains
polysaccharides but little cordycepin. A
product claiming 40% polysaccharides
means very little. Beta-D-glucan levels in
mycelium grain range in one study, from
7.85-10.9% (Chilton, 2016).
A fermented O. sinensis product,
corbrin capsule, has been investigated
for thyroid health. Work by He et
al. (2016) looked at 44 patients with
Grave’s disease and 56 patients with
Hashimoto’s thyroiditis. These patients
were divided into treatment and control
groups. After 24 weeks, the balance
between helper T and cytotoxic T cells
in both groups was restored due to
immune modulating effects.
But a close cousin (to O. sinensis) is
relatively easy to propagate organically,
leading to new scientific findings
of health benefits and increased
consumer demand for the fruiting body
medicine. Bei chong chaw or “northern
wormgrass” (C. militaris [L.] Fr.) is
widely used in TCM for immunity,
metabolism and the nervous system. It
is gaining increased popularity in both
the scientific and consumer worlds. (For
information on how YOU can cultivate
this fungus, see “Home Cultivator” in
this issue of FUNGI.)
Kang et al. (2015) studied the
effects of C. militaris for enhancing
cell-mediated immunity and safety. A
group of 79 healthy males was divided
into experimental and control, and
given one and a half grams daily of
capsules. The mushroom enhanced NK
(natural killer) cell activity, lymphocyte
proliferation and partially increased
Th1 cytokine secretion.
Submerged mycelium cultures of
O. sinensis and C. militaris have been
investigated for anti-tumor effect. Work
by Avtonomova et al. (2015) found doses
of O. sinensis and C. militaris given to
mice with subcutaneously inoculated
P388 leukemia cell lines lowered tumor
growth by 65% and 54% respectively.
However, the former product (O.
sinensis) accelerated the growth of the
tumor node almost two times, compared
to control, suggesting undesirable tumor
stimulating effect.
Cerebrosides, isolated from cultivated
fruiting bodies of C. militaris, inhibit
the pro-inflammatory iNOS protein
and reduce expression of COX-2,
suggestive of anti-inflammatory
activity (Chiu et al., 2016). Cordycepin
(3-deoxyadenosine) not only controls
tumor cell proliferation but induces
cancer cell apoptosis (Tian et al., 2015).
Cordycepin induces apoptosis (self-
programmed death) in vivo in human
breast cancer cells by reducing cell
viability, inhibition of cell proliferation,
induced mitochondrial dysfunction and
apoptosis; and by increasing activation
of caspase-8, caspase-9, caspase-3 and
Bax, and suppression of anti-apoptotic
protein, B-cell lymphoma 2 (Bcl-2)
(Wang et al., 2016). Cordycepin differs
from adenosine in that its ribose lacks
an oxygen atom at the 3’ position. The
compound possesses anti-viral activity
against influenza, HIV, murine leukemia
and Epstein-Barr (EBV) (Ryu et al.,
2014). Du et al. (2016) looked at the
presence of Epstein-Barr in various
tumor cells. They found cordycepin
enhanced the efficacy of conventional
chemotherapy (doxorubicin) in treating
EBV positive tumors.
Water extracts of C. militaris induce
in vivo apoptosis in liver and breast
cancer cell lines, via the caspase-
dependent mitochondrial pathway
(Song et al., 2016b). Cordycepin may be
useful on its own, or as an adjuvant in
the treatment of gallbladder cancer (Wu
et al., 2014). Ethanol extracts inhibit
human colorectal (RKO) cell lines, due
to induction of cell cycle arrest and
mitochondrial-mediated apoptosis
(Lee et al., 2015). Cordycepin appears
to reduce inflammation associated
FUNGI Volume 10:1 Spring 2017 43
with progression to intervertebral disc
degeneration (Li et al., 2016). Ethanol
extracts of C. militaris promote neurite
outgrowth, suggesting benefit for brain
and cognitive health (Phan et al., 2013).
The fruiting body, in work by
Bizarro et al. (2015), has been found
to increase cellular levels of p53 and
p21 and reduce growth of non-small
cell lung cancer cell lines. Cultivated
fruiting bodies activates p38, showing
potential to induce apoptosis in human
leukemia cancer cell lines (Chou et
al., 2015). Previous work by Cho et al.
(2014) examined hot water extracts
of C. militaris mycelia and cultivated
fruiting bodies. The fruiting body was
found more cytotoxic against human
leukemia cells, but when cordycepin
was supplemented in the mycelium to
levels found in fruiting body, the levels
of induced apoptosis were similar.
This is interesting as work by Chan et
al., (2015) looked at the composition
of fruiting body and mycelium in this
species. The fruiting body contained
0.11% cordycepin and mycelia content
was 0.182%, while ergothioneine
content was 782 mg/kg in former and
only 130 mg/kg in mycelium. The
fruiting body contains higher levels
of calcium, potassium, sulfur and
magnesium, while the mycelium was
richer in sodium and phosphorus.
The gene p53 is involved in protecting
from cancer by constantly surveying
the division of cells, inducing self-
programmed death (apoptosis) in
rogue cells. The book p53: the Gene
that Cracked the Cancer Code by Sue
Armstrong (2015) is well worth a read.
Extracts from fruiting bodies
suppress tumor growth of human
malignant melanoma cells by inhibiting
angiogenesis (Ruma et al., 2014). This is
the mechanism by which solid tumors
are denied the blood supply necessary to
feed them. A two week anti-fatigue study
of mice was conducted by Song et al.
(2015) using C. militaris fruiting bodies.
Compared to non-treated mice, the levels
of ATP increased, lactic acid reduced and
a number of pathways showed significant
benefit against fatigue.
Cordyceps has been found to
ameliorate the nephrotoxicity associated
with cyclosporine, an anti-rejection drug
used with organ transplant patients (Bao
et al.,1994). Cyclosporine was initially
44 FUNGI Volume 10:1 Spring 2017
derived from the anamorph of Cordyceps
subsessilis (Tolypocladium inflatum).
The use of C. sinensis with low
doses of cyclosporine, shows benefit
in kidney transplant patients and
less complications than drug alone.
Levels of IL-2 were similar but the
anti-inflammatory cytokine IL-10 was
significantly higher in Cordyceps group
(Ding et al., 2011). Recent work has
found water extracts of the fruiting
body of C. militaris protects against
glomerulonephritis, by reducing
inflammatory cytokine levels (Song
et al., 2016a). Exopolysaccharides
produced by C. militaris decrease
production of uric acid and provide
more potential efficacy of kidney
protection than the drug allopurinol
(Ma et al., 2014).
A combination of fruiting body and
mycelium shows strong hypoglycemic
activity with lowered levels of
cholesterol and triglycerides in a mice
study by Yu et al. (2015). It appears
to lower blood glucose by increasing
insulin sensitivity, and PPAR-gamma
expression in adipose tissue that
restored triglyceride and cholesterol
levels. Recent work (Liu et al., 2016)
with rat models found supplementation
with Cordyceps protects pancreatic
beta cells. Previous work found it
improved the activity and secretory
function of the pancreatic islet beta
cells. Cordycepin and the mushroom
C. militaris were studied for the ability
to suppress bone loss and inhibit
osteoblast differentiation. Work by Kim
et al. (2015) suggests supplementation of
both may be useful in helping maintain
bone health.
Cordycepin, isolated from C.
militaris, has been studied for its anti-
depressant effects. Work by Tianzhu et
al. (2014) found cordycepin up-regulates
BDNF (brain derived neurotrophic
factor) and down-regulates serotonin
levels (5-HT2AR) and inflammation in
the hippocampus.
Despite its higher production costs,
the availability of fruiting bodies of C.
militaris is poised to be the next wave
in the medicinal mushroom market.
Studies by Zhu et al. (2013) suggest
the fresh fruiting bodies are superior
to dried when compared, for immune
modulation. Freeze-drying, fresh fruiting
body tinctures, or extracts may be more
optimal. In China, the fruiting bodies are
often grown on silkworm castings.
References Cited
Armstrong, S. 2015. p53: the Gene that
Cracked the Cancer Code. Bloomsbury
Sigma. London, Oxford, New York.
Avtonomova, A.V., L.M. Krasnopolskaya,
M.I. Shuktueva, E.B. Isakova, and
V.M. Bukhman. 2015. Assessment
of antitumor effect of submerged
culture of Ophiocordyceps sinensis and
Cordyceps militaris. Antibiot Khimioter
60(7-8): 14-17.
Bao, Z.D., Z.G. Wu, and F. Zheng. 1994.
Amelioration of aminoglycoside
nephrotoxicity by Cordyceps sinensis in
old patients. Zhongguo Zhong Xi Yi Jie
He Za Zhi. 14(5): 271-273.
Bizarro, A., I.C. Ferreria, M. Sokovic,
L.J. van Griensven, D. Sousa, et al. 2015.
Cordyceps militaris (L.) link fruiting
body reduces the growth of a non-small
cell lung cancer cell line by increasing
cellular levels of p53 and p21. Molecules
20(8): 13927-13940.
Chan, J.S., G.S. Barseghyan, M.D. Asatiani,
and S.P Wasser. 2015. Chemical
composition and medicinal value of
fruiting bodies and submerged cultured
mycelia of caterpillar medicinal fungus
Cordyceps militaris CBS-132098
(Ascomycetes). International Journal of
Medicinal Mushrooms 17(7): 649-659.
Chilton, J. 2016. A new analytical
fingerprinting method for quality
control of medicinal mushroom
products. International Society for
Mushroom Science. Science and
Cultivation of Edible Fungi. Baars &
Sonnenbert (Eds.).
Chiu, C.P., S.C. Liu, C.H. Tang, Y. Chan,
M. El-Shazly, C.L. Lee, et al. 2016.
Anti-inflammatory cerebrosides from
cultivated Cordyceps militaris. Journal
of Agricultural and Food Chemistry
64(7): 1540-1548.
Chou, S.M., W.J. Lai, T.W. Hong, J.Y. Lai,
S.H. Tsai, Y.H. Chen, S.H. Yu, et al. 2014.
Synergistic property of cordycepin in
cultivated Cordyceps militaris-mediated
apoptosis in human leukemia cells.
Phytomedicine 21(12): 1516-1524.
Chou, S.M., W.J. Lai, T. Hong, S.H. Tsai,
Y.H. Chen, C.H. Kao, R. Chu, T.L.
Shen, and T.K. Li. 2015. Involvement
of p38 MAPK in the anticancer activity
of cultivated Cordyceps militaris.
American Journal of Chinese Medicine
 43(5): 1043-1057.
Ding, C., P.X. Tian, W. Xue, X. Ding,
H. Yan, X. Pan, X. Feng, et al. 2011.
Efficacy of Cordyceps sinensis in long
term treatment of renal transplant
patients. Front Biosci (Elite Ed)
3: 301-307.
Du, Y., J. Yu, L. Du, J. Tang, and W.H. Feng.
2016. Cordycepin enhances Epstein-
Barr virus lytic infection and Epstein-
Barr virus-positive tumor treatment
efficacy by doxorubicin. Cancer Letters
376(2): 240-248.
He, T., R. Zhao, Y. Lu, W. Li, X. Hou,
Y. Sun, M. Dong, and L. Chen. 2016.
Dual-directional immunomodulatory
effects of corbrin capsule on
autoimmune thyroid diseases. Evidence
Based Complementary and Alternative
Medicine (Article ID 1360386).
Kang, H.J., H.W. Baik, S.J. Kim, S.G. Lee,
H.Y. Ahn, J.S. Park, S.J.Park, et al. 2015.
Cordyceps militaris enhances cell-
mediated immunity in healthy Korean
men. Journal of Medicinal Food 18(10):
1164-1172.
Kim, J., H. Lee, K.S. Kang, K.H. Chun,
and G.S. Hwang. 2015. Cordyceps
militaris mushroom and cordycepin
inhibit RANKL-induced osteoclast
differentiation. Journal of Medicinal
Food 18(4): 446-452.
Lee, H.H., S. Lee, K. Lee, Y.S. Shin, H. Kang,
and H. Cho. 2015. Anti-cancer effect of
Cordyceps militaris in human colorectal
carcinoma RKO cells via cell cycle arrest
and mitochondrial apoptosis. DARU
Journal of Pharmaceutical Sciences doi:
10.1186/s40199-015-0117-6.
Li, Y., K. Li, L. Mao, X. Han, K. Zhang,
C. Zhao, and J. Zhao. 2016. Cordycepin
inhibits LPS-induced inflammatory
and matrix degradation in the
intervertebral disc. Peer Journal 10(4):
e1992. 10.7717(peerj.1992).
Liu, H., D. Cao, H. Liu, K. Liu, W. Mai,
H. Lan, W. Huo, and Q. Zheng. 2016.
The herbal medicine Cordyceps
sinensis protects pancreatic beta
cells from streptozotocin-induced
endoplasmic reticulum stress.
Canadian Journal of Diabetes doi:
10.1016/j.jcjd.2016.02.001.
Ma, L., S. Zhang, Y. Yuan, and J. Gao.
2014. Hypouricemic actions of
exopolysaccharide produced by
Cordyceps militaris in potassium
oxonate-induced hyperuricemic mice.
Current Microbiology 69(6): 852-857.
Phan, C.W., P. David, M. Naidu, K.H.
Wong, and V. Sabaratnam. 2013.
Neurite outgrowth stimulatory effects
of culinary-medicinal mushrooms
and their toxicity assessment
using differentiating Neuro-2a and
embryonic fibroblast BALB/3T3.
BMC Complementary and Alternative
Medicine 13: 261.
Ruma, I.M., E.W. Putranto, E. Kondo,
R. Watanabe, K. Saito, Y. Inoue, et al.
2014. Extract of Cordyceps militaris
inhibits angiogenesis and suppresses
tumor growth of human malignant
melanoma cells. International Journal
of Oncology 45(1): 209-218.
Ryu, E., M. Son, M. Lee, K. Lee, J.Y. Cho,
S. Cho, S.K. Lee, Y.M. Lee, H.
Cho, G.H. Sung, and H. Kan. 2014.
Cordycepin is a novel chemical
suppressor of Epstein-Barr virus
replication. Oncoscience 1(12):866-881.
Song, J., Y. Wang, M. Teng, G. Cai, H. Xu,
H. Guo, Y. Liu, D. Wang, and L. Teng.
2015. Studies on the anti-fatigue
activities of Cordyceps militaris fruit
body extract in mouse model. Evidence
Based Complementary Alternative
Medicine doi: 10,1155/2015/174616.
Song, J., Y. Wang, M. Teng, S. Zhang,
M. Yin, et al. 2016b. Cordyceps
militaris induces tumor cell death via
the caspase-dependent mitochondrial
pathway in HepG2 and MCF-7 cells.
Molecular Medicine Reports 13(6):
5132-5140.
Song, J., Y. Wang, C. Liu, Y. Huang, L.
He, X. Cai, J. Lu, Y. Liu, and D. Wang.
2016a. Cordyceps militaris fruit body
extract ameliorates membranous
glomerulonephritis by attenuating
oxidative stress and renal inflammation
via the NF-kB pathway. Food and
Function 7(4): 2006-2015.
Tian, X., Y. Li, Y. Shen, Q. Li, Q. Wang,
and L. Feng. 2015. Apoptosis and
inhibition of proliferation of cancer
cells induced by cordycepin. Oncology
Letters 10(2): 595-599.
Tianzhu, Z., Y. Shihai, and D. Juan. 2014.
Antidepressant-like effects of
cordycepin in a mice model of chronic
unpredictable mild stress. Evidence
Based Complementary Alternative
Medicine doi: 10.1155/2014/438506.
Wang, D., Y. Zhang, J. Lu, Y. Wang, J.
Wang, Q. Meng, R.J. Lee, D. Wang,
and L. Teng. 2016. Cordycepin, a
natural antineoplastic agent, induces
apoptosis of breast cancer cells via
caspase-dependent pathways. Natural
Product Communications 11(1): 63-68.
Wu, W.D., Z.M. Hu, M.J. Shang, D.J.
Zhao, C.W. Zhang, D.F. Hong, and
D.S. Huang. 2014. Cordycepin down-
regulates multiple drug resistant
(MDR)/HIF-1alpha through regulating
AMPK/mTORC1 signaling in GBC-SD
gallbladder cancer cells. International
Journal of Molecular Sciences 15(7):
12778-12790.
Yu, S.H., S.Y. Chen, W.S. Li, N.K.
Dubev, W.H. Chen, et al. 2015.
Hypoglycemic activity through a
novel combination of fruiting body
and mycelia of Cordyceps militaris in
high-fat diet-induced type 2 diabetes
mellitus mice. Journal of Diabetes
Research 2015:723190.
Zhu, S.J., J. Pan, B. Zhao, J. Liang,
W. Ze-Yu, and J.J. Yang. 2013.
Comparisons on enhancing the
immunity of fresh and dry Cordyceps
militaris in vivo and in vitro. Journal of
Ethnopharmacology 149(3): 713-719.
FUNGI Volume 10:1 Spring 2017 45