Serial Review

J. Clin. Biochem. Nutr., 40, 157162, May 2007

Recent Advances in Indian Herbal Drug Research

Guest Editor: Thomas Paul Asir Devasagayam

Indian Medicinal Mushrooms as a Source of Antioxidant and

Antitumor Agents
Thekkuttuparambil A. Ajith1 and Kainoor K. Janardhanan2,*
1

Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur, Kerala-680 555, India
Department of Microbiology, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala-680 555, India

Received 19 September, 2006; Accepted 6 December, 2006

Summary Medicinal mushrooms occurring in South India namely Ganoderma lucidum,

Phellinus rimosus, Pleurotus florida and Pleurotus pulmonaris possessed profound antioxidant
and antitumor activities. This indicated that these mushrooms would be valuable sources of
antioxidant and antitumor compounds. Investigations also revealed that they had significant
antimutagenic and anticarcinogenic activities. Thus, Indian medicinal mushrooms are
potential sources of antioxidant and anticancer compounds. However, intensive and extensive
investigations are needed to exploit their valuable therapeutic use.
Key Words: antioxidant, antitumor, medicinal mushroom
compounds function in human system are increasingly being
established [3]. Medicinal mushrooms have an established
history of use in traditional oriental medicine. Many
traditionally used mushrooms from genera, Auricularia,
Flammulina, Ganoderma, Grifola, Lentinus, Trametes
(Coriolus) and Tremella have been demonstrated to possess
significant medicinal properties [2].
Great threat to human life by neoplastic diseases continues
to increase and thus the pursuit for anti-tumor drugs takes a
compelling urgency. Attempts have been made in many
parts of the world to explore the use of mushrooms and their
metabolites for the treatment of a variety of human ailments
[4]. The most significant medicinal effect of mushrooms and
their metabolites that have attracted the attention of the
public is their antitumor property. Lucas and his collaborators first demonstrated the antitumor activity of the higher
Basidiomycetes in 1957 [5].
The significant pharmacological effects and physiological
properties of mushrooms are bioregulation (immune enhancement), maintenance of homeostasis and regulation of biorhythm, cure of various diseases and prevention and

Introduction
Many clinically used drugs such as aspirin, digitoxin,
progesterone, cortisone, morphine, vincristine, vinblastine,
taxol and several others are derived directly or indirectly from
higher plants. Clinically important and well recognized drugs
of fungal origin are penicillin, griseofulvin, ergot alkaloids
and cyclosporine. Among the large resources of fungi, higher
Basidiomycetes especially mushrooms are unlimited sources
of therapeutically useful biologically active agents. There
are approximately 700 species of higher Basidiomycetes that
have been found to possess significant pharmacological
activities [1, 2]. Modern scientific studies on medicinal
mushrooms have expanded exponentially during the last two
decades not only in Japan, Korea and China but also in
USA and scientific explanation to show mushrooms derived
*To whom correspondence should be addressed.
Fax: 91-487-2307020, 2307868
E-mail: [email protected]
157

158

T.A. Ajith and K.K. Janardhanan

improvement from life threatening diseases such as cancer,

cerebral stroke and heart diseases. Mushrooms are also
known to have effective substances for antifungal, antiinflammatory, antitumor, antiviral, antibacterial, hepatoprotective, antidiabetic, hypolipedemic, antithrombotic and
hypotensive activities [6].
The oxidative properties of oxygen play a vital role in
diverse biological functions such as utilization of nutrients,
electron transport to produce ATP and the removal of xenobiotics [7]. While oxygen is essential for life, it also can
provoke damaging oxidative events within cells. Oxygen, by
its transformation to more reactive forms i.e., superoxide
radical (O2), hydroxyl radical (OH) and hydrogen peroxide
(H2O2) can nick DNA, can damage essential enzymes
and structural proteins and can also provoke uncontrolled
chain reactions, such as lipid peroxidation or autooxidation
reactions (e.g. polymerization of catecholamines) [8, 9].
Oxygen derived free radicals are generated during the
oxidative metabolism and energy production in the body and
are involved in the regulation of signal transduction and gene
expression, activation of receptors and nuclear transcription
factors. Overwhelming evidences indicate that oxidative
stress can lead to cell and tissue injury. In most of the cases
free radicals are secondary to the diseases but in some
instances they are causal. In addition to reactive oxygen
species (ROS), researches on reactive nitrogen species
(RNS) are gathering momentum, an area of enormous
importance in biology and medicine. Current hypothesis
favors the idea that lowering oxidative stress can be a health
benefit.
The antioxidant status in human reflects the dynamic
balance between the antioxidant defence and prooxidant
conditions and this has been suggested as a useful tool in
estimating the risk of oxidative damage [10]. ROS have been
implicated in the pathophysiology of various clinical disorders,
including ischemia, reperfusion injury, myocardial infarction,
rheumatoid arthritis, neurodegenerative, atherosclerosis, acute
hypertension, hemorrhagic shock and diabetes mellitus [7].

Selected Examples of Indian Medicinal Mushrooms

with Antioxidant and Antitumor Activities
Over the last 23 decades scientific studies carried out
in Japan, China, Korea and more recently in USA have
increasingly demonstrated the potent and unique health
enhancing properties of compounds and extracts of range
of medicinal mushrooms. However, only a limited number
of mushrooms available in India till now are investigated
for their pharmacological properties. Nevertheless, recent
investigations in our laboratory revealed that a number of
medicinal mushrooms occurring in South India possessed
promising antioxidant and anticancer properties.

Phellinus rimosus
Phellinus is a large and widely distributed genus of the
family Hymenochetaceae. (Donk) under the class, Basidiomycetes. The species are mostly confined to the plains/
tropical forests. Environmental factors such as temperature,
humidity, light and host trees are very important for development of basidiocarps. The dominant and most frequently
found species are Phellinus (P. senex), P. rimosus, P. badius,
P. fastuosus, P. adamantinus, P. caryophylli and P. durrissimus
[11]. About 18 species are found to occur in Kerala, most of
them are wood inhabiting [12]. P. rimosus (Berk) Pilat is
found growing on jackfruit tree trunks in Kerala. In Kerala,
this mushroom is commonly found on living Moraceae
members.
In Chinese medicine hot water extract of the fruiting
bodies of Phellinus species have been used for an extensive
range of ailments and it is believed to work as a miracle
drug refreshing the human body and prolong longevity
[13]. Recent studies have compared hot water extract of
Phellinus with other anticancer mushrooms. The Phellinus
extract showed the strongest evidence of tumor proliferation
suppression [14].
Ethyl acetate, methanol and aqueous extracts of the P.
rimosus were effective to scavenge O2 generated from
the photoillumination of riboflavin, OH generated from
Fentons reaction, nitric oxide radical released from aqueous
solution of sodium nitroprusside in a dose dependent manner
[1517]. The extracts inhibited dose dependently ferrous ion
induced lipid peroxidation in the rat whole liver homogenate.
The effective concentrations required to scavenge 50% of
generated radicals (IC50) are given in Table 1. Methanol
extract of P. rimosus effectively reduced ferric ion in FRAP
assay and scavenged DPPH radicals (Fig. 1).
All the three extracts when tested for antitumor activity
were found to inhibit the Daltons Lymphoma Ascites
(DLA) cell line induced solid tumor in mice and Ehrlichs
Ascites Carcinoma (EAC) cell line induced ascites tumor in
mice [18]. The antitumor effect was found to be higher for
the ethyl acetate extract than other extracts (Fig. 2). The
results indicated that the extracts of P. rimosus possessed
profound antitumor activity.
Ganoderma lucidum
Ganoderma lucidum (G. lucidum) and related species
have the longest historical usage for medicinal properties
dating back at least four thousand years [19]. In Japan it
is called Reishi and in China and Korea it is variously
called Ling Chu and Ling Zhi (Mushroom of immortality).
Traditionally it has been used widely in the treatment of
hepatopathy, chronic hepatitis, nephritis, hypertension,
arthritis, insomnia, bronchitis, asthma and gastric ulcer.
Scientific studies have confirmed that the substances
extracted from the mushrooms can reduce blood pressure,
J. Clin. Biochem. Nutr.

Indian Medicinal Mushrooms: Antioxidant and Antitumor Agents

159

Table 1. In vitro antioxidant activity of ethyl acetate (EtOAC), methanol (MeOH) and aqueous
(AQ) extracts of P. rimosus (Pr), G. lucidum (Gl), P. florida (Pf), and P. pulmonarius
(Pp).
IC50 (g/ml)
Extracts

Super oxide
scavenging

Nitric oxide
scavenging

Hydroxyl radical
scavenging

EtOAc

22.0 1.0
(Pr)

(Pf)

438.0 21.6
(Pr)

(Pf)

68.0 4.1
(Pr)
530.0 29.4
(Pf)

162 7.0
(Pr)
496.0 4.7
(Pf)

MeOH

25.3 1.2
(Pr)
152.5 2.5
(Gl)

(Pp)

(Pf)

126.7 12.6
(Pr)

(Gl)

(Pp)

(Pf)

93.0 10.3
(Pr)
560.0 0.1
(Gl)
476.7 24.6
(Pp)
263.3 24.9
(Pf)

282 12.8
(Pr)
873.5 7.2
(Gl)
960.0 10.0
(Pp)
320.0 10.0
(Pf)

AQ

126.0 5.1
(Pr)
475.0 25.0
(Gl)

(Pf)

31.0 4.5
(Pr)

(Gl)

(Pf)

71.0 4.7
(Pr)
140.0 2.0
(Gl)
263.3 24.9
(Pf)

318 2.4
(Pr)

(Gl)

(Pf)

Lipid peroxidation
inhibiting

Values are mean SD, n = 3. Names of mushrooms included in the parenthesis.

Fig. 2.
Fig. 1.

Ferric ion reducing and DPPH radical scavenging activities of methanol extract of P. rimosus. Values are
mean SD, (n = 4). Activities are expressed in equivalent concentrations of trolox.

blood cholesterol and blood sugar level as well as inhibition

of platelet aggregation.
Ganoderma species are famous tonic in Chinese medicines.
They are widely distributed in India on tree trunks. Ganoderma
belongs to the polyporaceae family of Basidiomycota.
Generally Ganoderma species are described as beneficial to all
viscera and non-toxic [20]. For 4000 years G. lucidum has been
Vol. 40, No. 3, 2007

Antitumor activity of ethyl acetate (EtOAc), methanol

(MeOH) and aqueous (AQ) extracts of P. rimosus (Pr),
G. lucidum (Gl), P. florida (Pf) and P. pulmonaris (Pp)
against EAC induced solid tumor in mice.

used as a part of Chinese and Japanese medicine especially

for the treatment of most of the human ailments including
chronic hepatitis, nephritis, hepatopathy, neurasthenia, arthritis,
bronchitis, asthma, gastric ulcer etc.
Extracts from fruiting bodies and mycelia of G. lucidum
occurring in South India were found to possess in vitro antioxidant activity [21, 22] and antimutagenic activities [22]

160

T.A. Ajith and K.K. Janardhanan

The results of the antioxidant assays showed that ethyl acetate, methanol and aqueous extract of G. lucidum effectively
scavenged the O2 and OH radicals (Table 1). However the
aqueous extract was not effective to inhibit the ferrous ion
induced lipid peroxidation [21]. The extract showed significant reducing power and radical scavenging property as evident from FRAP assay (Fig. 3) and DPPH radical scavenging assay (Fig. 4) [23]. The extract of G. lucidum also effectively to inhibited EAC cell line induced solid tumor in
mice when administered orally (Fig. 2) [21]. The prophylactic treatment by the extract could inhibit the tumor growth
significantly or increased the life span.
Pleurotus species
Pleurotus species have high medicinal value. Compounds
extracted from these mushrooms exhibit activity against
various chronic diseases including hypertension, hyper-

cholesterolemia [2426]. The medicinal beneficial effects of

Pleurotus species were discovered independently in different
countries. The awareness of their medicinal properties came
not only from Asia but from the folklore of central Europe,
South America and Africa [25].
Oyster mushrooms (Pleurotus species) are excellently
edible and nutritious, rank among one of the most widely
cultivated mushrooms in the world [27]. Species of Pleurotus
are found to possess significant antioxidant, anti-inflammatory
and antitumor activities [28, 29]. The methanol extract of
fruiting bodies of Pleurotus florida was found to possess

OH radical scavenging and lipid peroxidation inhibiting

activities (Table 1) [28]. The extract also showed significant
reducing power and radical scavenging property as evident
from FRAP assay (Fig. 3) and DPPH radical scavenging
assay (Fig. 4) [23].
Methanol extract of the fruiting bodies of Pleurotus
florida [28], Pleurotus pulmonarius [29] occurring in South
India showed profound antitumor activity against the
Ehrlichs ascites carcinoma (EAC) cell line induced solid
tumor model in mice (Fig. 2).

Current Status

Fig. 3.

Ferric ion reducing property of aqueous extract of

Pleurotus florida (Pf) and G. lucidum (Gl) using FRAP
assay. Values are mean SD, (n = 4). The reducing
capacity is expressed in equivalent concentrations of
ascorbic acid.

Fig. 4.

DPPH radical scavenging activity of aqueous extract

of Pleurotus florida (Pf) and G. lucidum (Gl). Values
are mean SD, (n = 4). The scavenging activity is
expressed in equivalent concentrations of ascorbic acid.

The National Cancer Institute (NCI), United States has

recently intensified its emphasis upon natural products such
as plants, marine organisms and selected class of microorganisms as sources for new drug discovery. Screening of
plant extracts for anticancer activity began at NCI in 1956.
Many of the currently available and clinically useful anticancer drugs are either natural plant products or derivatives of
natural products e.g. paclitaxel (Taxol) from Taxus brevifolia
and vincristin (Oncovin) from Catharanthus roseus [30].
Plants continue to offer a wide range of compounds with
diverse structure and activities in modern cancer therapy.
Ikekawa et al. [31] published one of the first scientific
reports on antitumor activity of extracts of mushrooms against
implanted Sarcoma 180 in animals. Soon after, three major
anticancer drugs, Krestin from cultured mycelium of Trametes
(Coriolus versicolor), Lentinan from fruiting bodies of Lentinus
edodus and Scizophyllan from Schizophyllum commune,
were developed [6, 32, 33]. While much attention has been
drawn to various immunological and anticancer properties
of these mushrooms they offer other potentially important
therapeutic properties including antioxidant, antihypertensive,
antidiabetic, anti-inflammatory, hepatoprotective etc. Several
mushroom derived compounds are now increasingly used in
Japan, Korea and China as adjuvant to standard radio- and
chemotherapy. The most encouraging effect is the ability of
these mushroom derived compounds when administered prior
to or during radio- or chemotherapy significantly reduced
the side effects from these treatments.
Reactive oxygen and nitrogen species are implicated in
J. Clin. Biochem. Nutr.

Indian Medicinal Mushrooms: Antioxidant and Antitumor Agents

the pathophysiology of several diseases. Oxidative damage

to DNA may initiate carcinogenesis. Most mushrooms
derived preparations and substances find their use not as a
pharmaceutical but as a novel class of dietary supplement
(DS) or nutraceuticals that fall very well into the concept of
functional food. Dietary chemotherapeutic agents may serve as
potent agents for enhancing therapeutic effect of chemotherapy,
radiotherapy and offer standard therapies for the treatment
of human cancer [34]. Mushrooms derived compounds have
been shown to possess potent antitumor activities in both
pre-clinical models and clinical trails. The safety criteria of
these compounds have been exhaustively studied with little
evidence of toxicity.

Conclusions
Recent investigations carried out in our laboratory showed
that medicinal mushrooms occurring in South India namely
Ganoderma lucidum, Phellinus rimosus, Pleurotus florida
and Pleurotus pulmonaris possessed profound antioxidant
and antitumor activities. This indicated that these mushrooms would be valuable sources of antioxidant an antitumor compounds. Investigations also showed that they had
significant antimutagenic and anticarcinogenic activies. Thus,
Indian medicinal mushrooms are potential sources of antioxidant and anticancer compounds. However, intensive and
extensive investigations are needed to exploit their valuable
therapeutic use.

References
[1] Mizuno, T.: Bioactive biomolecules and mushrooms: food
function and medicinal effects of mushroom fungi. Food Rev.
Int., 11, 721, 1995.
[2] Wasser, S.P.: Medicinal mushrooms as a source of antitumor
and immunomodulatory polysaccharides. Appl. Microbiol.
Biotechnol., 60, 258274, 2002.
[3] Zaidman, B., Yassin, M., Mahajana, J., and Wasser, S.P.:
Medicinal mushrooms modulators of molecular targets as
cancer therapeutics. Appl. Microbiol. Biotechnol., 67, 453
468, 2005.
[4] Jong, S.C. and Birmingham, J.M.: Medicinal benefits of the
mushroom Ganoderma. Adv. Appl. Microbiol., 37, 101134,
1992.
[5] Lucas, E.H., Montesono, R., Pepper, M.S., Hafner, M., and
Sablon, E.: Tumor inhibitors in Boletus edulis and other
holobasidiomycetes. Antibiot. Chemother., 7, 14, 1957.
[6] Wasser, S.P. and Weis, A.L.: Medicinal properties of
substances occurring in higher basidiomycetes mushrooms:
current perspective (review). Int. J. Med. Mushr., 1, 3162,
1999.
[7] Hemnani, T. and Parihar, M.S.: Reactive oxygen species and
oxidative DNA damage. Ind. J. Physiol. Pharmacol., 42,
440452, 1998.

Vol. 40, No. 3, 2007

161

[8] Bijalani, R.L.: Physiology of aging, in Understanding

medical Physiology, ed. By Bijlani, R.L., Jaypee Brothers
Medical Publications Private Ltd., New Delhi, pp. 3842,
1995.
[9] Halliwell, B. and Cross, C.E.: Oxygen-derived species: Their
relation to human disease and environmental stress. Environ.
Health Perspect., 102, 512,1994.
[10] Tiwari, A.K.: Antioxidant: New generation therapeutic base
for treatment of polygenic disorders. Curr. Sci., 86, 1092
1102, 2004.
[11] Sharma, J.R.: Ecology and distribution of Hymenochaetaceae,
in Hymenochaetaceae of India, ed. By Sharma, J.R., Botanical
Survey of India, Culcutta, India, pp. 910, 1995.
[12] Leelavathy, K.M. and Ganesh, P.N.: Polypores in Kerala.
Daya Publishing House, Delhi, India, pp. 5060, 2000.
[13] Ying, J.Z., Mao, X,L., Ma, Q.M., Zong, Y.C., and Wen, H.A.:
Icons of medicinal fungi from China (Transl. Xu, Y.H.), in Illustrations of of Chinese medicinal fungi, eds. By Ying, J.Z.,
Mao, X.L., Ma, Q.M., Zong, Y.C., and Wen, H.A., Science
Press, Beijing, pp. 579585, 1987.
[14] Mizuno, T.: Development of an antitumor biological response
modifier from Phellinus linteus (Berk.Et.Curt) Teng
(Aphillophoromycetideae) (review). Int. J. Med. Mushr., 2,
2133, 2000.
[15] Ajith, T.A. and Janardhanan, K.K.: Antioxidant and antiinfammatory activities of methanol extract of Phellinus
rimosus. Ind. J. Exp. Biol., 39, 11661169, 2001.
[16] Ajith, T.A. and Janardhanan, K.K.: Antioxidant and antihepatotoxic activities of Phellinus rimosus (Berk) Pilat. J.
Ethnopharmacol., 81, 387391, 2002.
[17] Ajith, T.A. and Janardhanan, K.K.: Chemopreventive activity of
a macrofungus Phellinus rimosus against N-nitrosodiethylamine
induced hepatocellular carcinoma in rat. J. Exp. Ther. Oncol.,
5, 309321, 2006.
[18] Ajith, T.A. and Janardhanan, K.K.: Cytotoxic and antitumor
activities of a polypore macrofungus, Phellinus rimosus. J.
Ethnopharmacol., 84, 157162, 2003.
[19] Zhao, J.D. and Zhang, X-Q.: Resources and taxonomy of
Ling Zhi (ganoderma) in China. Int. Symp.Gganoderma Res.,
Beijing, Bejing Medical University. 1994.
[20] Liu, G-T.: Recent advances in research of pharmacology
and Clinical application of Ganoderma (P. Karst) species
(Aphyllophoromycetideae) in China. Int. J. Med. Mushr., 1,
6367, 1999.
[21] Jones, S. and Janardhanan, K.K.: Antioxidant and antitumor
activity of Ganoderma lucidum (Curt.: Fr.) P. Karst.-Reishi
(Aphyllophoromycetideae) from South India. Int. J. Med.
Mushr., 2, 195200, 2000.
[22] Lakshmi, B., Ajith, T.A., Sheena, M., Nidhi, G., and
Janardhanan, K.K.: Antiperoxidative, anti-inflammatory and
antimutagenic activities of ethanol extract of the mycelium of
Ganoderma lucidum occurring in South India. Teratogen.
Carcinogen. Mutagen., 22, 113, 2003.
[23] Lakshmi, B., Tilak, J.C., Adhikari, S., Devasagayam, T.P.A.,
and Janardhanan, K.K.: Evaluation of antioxidant activity of
selected Indian mushrooms. Pharmaceutical Biol., 42, 179
185, 2004.

162

T.A. Ajith and K.K. Janardhanan

[24] Gunde-Cimmerman, N., Freidrich, J., Cimmerman, A., and

Benicki, N.: Screening fungi for the production of an inhibitor
of HMG CoA reductase, production of mevinolin by the
fungi of the genus Pleurotus. FEMS Microbiol. Lett., 111,
203206, 1993.
[25] Gunde-Cimmerman, N.: Medicinal value of the genus
Pleurotus (Fr.) P. Kaest. (Agaricales s.l., Basidiomycetes).
Int. J. Med. Mushr., 1, 6980, 1999.
[26] Wasser, S.P.: Medicinal mushrooms as source of antitumor
and immunomodulating polysaccharides. Appl. Microbiol.
Biotechnol., 60, 258274, 2002.
[27] Chang, S.T.: Global impact edible and medicinal mushrooms
on human welfare in the 21st century: non green evolution.
Int. J. Med. Mushr., 1, 17, 1999.
[28] Jose, N. and Janardhanan, K.K.: Antioxidant and antitumor
activity of Pleurotus florida. Curr. Sci., 79, 941943, 2000.
[29] Jose, N., Ajith, T.A., and Janardhanan, K.K.: Antioxidant,

[30]
[31]

[32]

[33]
[34]

anti-inflammatory and antitumor activities of culinarymedicinal mushroom Pleurotus pulmonarius (Fr.) Quel.
(Agaricomycetideae). Int. J. Med. Mushr., 4, 329335, 2002.
Peuzuto, J.M.: Plant derived anticancer agents. Biochem.
Pharmacol., 57, 121133, 1997.
Ikekawa, T., Uehara, N., Maeda, Y., Nakanishi, M., and
Fukuoka, F.: Antitumor activity of aqueous extracts of edible
mushrooms. Cancer Res., 29, 734735, 1969.
Mizuno, T.: The extraction and development of antitumoractive polysaccharides from medicinal mushrooms in Japan
(review). Int. J. Med. Mushr., 1, 930, 1999.
Ikekawa, T.: Beneficial effects of mushrooms, edible and
medicinal, a health care. Int. J. Med. Mushr., 3, 7982, 2001.
Sarkar, F.H. and Li, Y.: Using chemoprevention agents to
enhance the efficacy of cancer therapy. Cancer Res., 66,
33473350, 2006.

J. Clin. Biochem. Nutr.