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Food and Nutrition Sciences, 2014, 5, 1095-1105
Published Online June 2014 in SciRes. http://www.scirp.org/journal/fns
http://dx.doi.org/10.4236/fns.2014.512119
How to cite this paper: Finimundy, T.C., Dillon, A.J.P., Henriques, J.A.P. and Ely, M.R. (2014) A Review on General Nutrition-
al Compounds and Pharmacological Properties of the Lentinula edodes Mushroom. Food and Nutrition Sciences, 5, 1095-
1105. http://dx.doi.org/10.4236/fns.2014.512119
A Review on General Nutritional Compounds
and Pharmacological Properties of the
Lentinula edodes Mushroom
Tiane Cristine Finimundy1, Aldo José Pinheiro Dillon2, João Antônio Pêgas Henriques1,
Mariana Roesch Ely1
1Laboratory of Genomics, Proteomics and DNA Repair, Institute of Biotechnology, University of Caxias do Sul,
Caxias do Sul, Brazil
2Laboratory of Enzyme and Biomass, Institute of Biotechnology, University of Caxias do Sul, Caxias do Sul, Brazil
Email: mrely@ucs.br
Received 1 March 2014; revised 20 April 2014; accepted 30 April 2014
Copyright © 2014 by authors and Scientific Research Publishing Inc.
This work is licensed under the Creative Commons Attribution International License (CC BY).
http://creativecommons.org/licenses/by/4.0/
Abstract
Lentinula edodes is a macrofungus with great potential for therapeutic applications and serves as a
model for investigating functional fungi properties and isolating pure compounds for pharmaceu-
tical use. Mushrooms have a great nutritional value and present medicinal molecules including
polysaccharides, terpenoids, sterols and lipids, that participate actively in several human disor-
ders and modulate mechanisms involved in the in the immune system regulation. This review will
focus on general nutritional compounds and pharmacological properties of L. edodes.
Keywords
Lentinula edodes, β-Glucans, Therapeutic Applications, Review
1. Introduction
Over the past 25 years, new natural drugs have been approved for the treatment of human diseases. Natural
products play a very important role in the process of discovery and development of drugs, including the treat-
ment of chronic diseases such as cancer [1]. For hundreds of years, medicinal mushrooms are used as decoctions
and essences, and are applied as alternative medicine in Korea, China, Japan and eastern Russia [2]. A wide va-
riety of compounds that occur naturally have proven active to protect against the development of tumors [3] and
inflammatory processes [4]. The most investigated compounds are polysaccharides which are present in the
whole structural composition mushrooms, among many effects are the antitumor and activation of the host
T. C. Finimundy et al.
1096
immune response [5]. A number of polysaccharides have been isolated from basidiomycete [6] and are
represented as homo- and heteropolymers, especially β-configuration glucans. One of the active compounds re-
sponsible for the immune effects is in the form of complex polysaccharides known as β-glucans, which are ubi-
quitously found in bacterial cell walls or yeast [7] [8]. The genus Lentinula sp. grows in gregarious on fallen
wood of a wide variety of deciduous trees, in a warm, moist climate. Most of these are raised for artificial
cultivation of shiitake mushroom and occurs naturally throughout Southeast Asia [9]. Lentinula edodes species
is the most famous (Figure 1), and has been used as a model to investigate the functional properties and isolate
pure compounds for pharmaceutical use.
L. edodes has shown to present medicinal compounds, including polysaccharides, terpenoids, sterols and li-
pids, which are effective in treating various tumors and infections, among other activities which are still being
studied [10].
In vitro and in vivo investigations have demonstrated the medicinal effect of glucans as modulators of humor-
al and cellular mediators of interleukin (IL), activators of macrophages, T-helper and natural killer (NK), pro-
tecting the body against bacteria, viruses, fungi and parasites. Modulation of the anti-inflammatory response has
also investigated [5]. In Japan, β-glucan is used as natural immunostimulant for cancer treatment since 1980.
β-Glucans are also effective against allogeneic, syngeneic, and even autochthonous tumors [11].
The literature has reported the presence of various compounds such as fractionated extract from mycelium L.
edodes (LEM) and the aqueous precipitate extract extracted from the mycelium (LAP). Both LEM and LAP
contains various sugars such as galactose, arabinose, xylose, mannose and fructose, among others [12]. These
extracts have revealed a strong anti-tumor activity in vivo. From the fractionation of LEM, lignin (80%), carbo-
hydrates (10%) and protein (10%) are obtained, together with a complex known as EP3 immuneactive [9] [13].
From the harvest of the mycelium, we also obtained amino acids (serine, threonine, alanine and proline), the
KS-2 peptide, α-mannan, which are capable of inducing the production of interferon and effectively inhibit the
development of cancer [14] [15].
Numerous clinical trials are currently under study in the USA and several European countries. Others Basi-
diomycetes species also present biologically active compounds of β-glucans like Pleuran for Pleurotus sp and
Lentinan for L. edodes [16]. Some of these important effects will be discussed in this review.
2. General Nutrition Componentes of L. edodes
Mushrooms have a great nutritional value since they are quite rich in protein, with an important content of es-
sential amino acids and fiber. The dietary fiber present in L. edodes (Shiitake) consist of soluble and insoluble
structures. In the water-soluble are found the β-glucans and proteins. In the non-soluble fraction, salts are ex-
tracted only with acids or alkalis, and found the polyuronide (acidic polysaccharide), hemicellulose, β-glucan
chains with heterosaccharide, lignin, and chitin. They also provide a nutritionally significant content of vitamins
(B1, B2, B12, C, D, and E) [17]. Are shown in Table 1 the main compounds. The aroma components include
alcohols, ketones, sulfides, alkanes, fatty acids, among others [13] [18]. The main constituents which are volatile
like matsutakeol (1-octen-3-ol) ethyl, n-amyl ketone and the characteristic aroma of shiitake was identified as
1,2,3,5,6-Pentathiepane [19]. Edible mushrooms are a high nutritional quality of food and have been used as an
Figure 1. Morphology of the Lentinula edodes.
T. C. Finimundy et al.
1097
Table 1. Main compounds found in edible mushrooms.
Fatty acid Free sugars Polysaccharides Trace elements
Soluble Insoluble Vitamins Minerals
Linoleic Trehalose Heteroglycans heteroglycan Pro-vitamin D-2 Fe
Palmitic Glycerol Heterogalactans polyuronide Pantothenic acid Mn
Tetradecenoic Mannitol Heteromannans β-glucan B1 Ca
Oleic Arabinol Xyloglucans Chitin B2 K
Stearic Mannose
B6 Zn
Myristic Arabinose
B12 Cd
alternative to dietary protein supply in countries with high malnutrition rate. The chemical and nutritional cha-
racteristics of mushrooms vary in function after harvest, and processing.
3. Immunomodulation and Anti-Tumour Effects of L. edodes
Edible mushrooms have been reported to generate beneficial effects on health and in the treatment of disease
through its immunomodulatory and antineoplastic properties [20]-[22].
Investigations related to the presence of anti-tumor substances present in mushrooms started in Japan in the
late 1960’s. Evaluations conducted with macrofungi confirmed the effectiveness of the extracts of the fruiting
bodies and mycelia in the inhibition of various cancer cell lines [2] [23]-[25]. The immunomodulatory effects of
the mushrooms are well described in the literature and are related to the increased function of monocytes in the
production of Interleukin-1 [11] [26] and expression of cytokines. Molecules like glucans are relatively resistant
to the stomach acid and are trapped by macrophage receptors present on the intestinal wall as the dectin-1, the
toll-like receptor 2 (a class of proteins that play a role in immune system) and lactosylceramides The β-glucans
with its various structures have different affinities for these receptors to elicit different host responses [16]. In
vivo studies showed that the analysis of cytokine expression after administration of β-glucan isolated from L.
edodes (lentinan) revealed a significant increase in mRNA levels of Interleukin-1α, interleukin-1β, tumor necro-
sis factor-α (TNF-α) and interferon-δ (IFN-δ).
This result indicates a good response in the homeostasis of various diseases (Figure 2) [27] [28].
To date its anti-tumor activity remains unclear as some authors relate this activity with increasing cell-medi-
ated immune response [29] [30]. However, other authors have shown anti-tumor activity with a direct effect on
the cell, without involving the immune system [31].
In a study to investigate the effect of lentinan on T cells, when administered intraperitoneally, resulted in
complete tumor regression in mice inoculated with cells FBL-3 (erythroleukemia).
The immunological effect was further confirmed when the inhibition of tumor growth stopped by administra-
tion of monoclonal antibodies against CD4 and CD8 prior to administration of β-glucan [32] [33]. These effects
could be helpful in a number of disease states, but the significance of some of these findings in terms of poten-
tial medicinal value still has to be established [34]-[36]. A recent clinical study showed that chemo-immuno-
therapy using lentinan prolongs the survival of patients with advanced gastric cancer, as compared to chemothe-
rapy alone [37]. In a study conducted by Lee et al. [38] crude water-soluble polysaccharides obtained from L.
edodes by hot water extraction and ethanol precipitation activated macrophages and showed the increased of ni-
tric oxide (NO), cytokines and phagocytosis expression.
An innovative strategy was suggested by Chen [39], using β-glucans to deliver nanoparticles containing che-
motherapeutic agents to the site of the colon cancer and, thus, improving the therapeutic efficacy.
The anti-tumour effects of shiitake feed in murine models has interact with the effects of lentinan, which has
been reported to prevent both chemical and viral carcinogenesis [40] [41].
Hazama et al. [42] demonstrated the efficacy of oral administration of lentinan in the treatment of advanced
colorectal cancer (Figure 3). Shimizu et al. [43] also revealed good results in advanced pancreatic cancer, both
with increased parameters of survival. Multicenter studies also looked at the effectiveness of the administration
of lentinan in patients with hepatocellular carcinoma, resulting in increased survival time of these patients [44]
[45].
T. C. Finimundy et al.
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Figure 2. Immune system activation and cytokine production.
Figure 3. Neutralization of immunosup-
pressive factors.
Yamaguchi et al. [46] suggests the concomitant use of L. edodes mycelia (LEM) extracts to chemotherapy,
resulting in a synergistic action to improve the quality of patients life. Another compound derived from the ex-
tract of L. edodes, the Active Hexose Correlated Compound (AHCC), also proved effective as adjunctive thera-
py in patients with cancer [47]-[49]. According to Ritz [49], oral supplementation with AHCC demonstrates a
potential clinically relevant agent that enhances the immune system.
Studies have shown that some active substances present in L. edodes exert a protective effect against mutage-
nesis and carcinogenesis [50]. Aqueous extracts of L. edodes demonstrated direct inhibition of the proliferation
of breast cancer cells in vitro and show to have immunostimulating properties in terms of mitogenic activity and
co-mitogenic (Figure 4) [51]. In addition, antimutagenic and antigenotoxic effects evaluated by micronucleus
and the comet test showed that extracts of shiitake have a antigenotoxic and antimutagenic activity in vivo [52]
[53].
However, further studies to define the relationship between exposure to the mutagen, the required amount of
Shiitake mushroom intake and the frequency of mutations, are still needed [52]. Basically, their antitumor abili-
ties are influenced by the molecular mass, branching configuration, conformation, and chemical modification of
the polysaccharides [36].
4. Antioxidant Effects of L. edodes
Our body has antioxidant defense systems that are often insufficient to completely prevent the damage caused
by oxidative stress [54]. Thus, natural products such as mushrooms containing bioactive compounds can be used
to help reduce such damage in the body [55]. As nutraceuticals, they activate endogenous protective system,
generation important antioxidant role for the homeostasis of the organism [18] [35] [54]. Several studies have
demonstrated the antioxidant properties of L. edodes for different; the extract on conditions. Study has performed
Tumor specific Ag
Macrophages
Granulocytes
β -glucan fragments
bind CR3
Tumor Cell
β-glucan
Dectin-1
Citokines ativation (IL-1, IL-2...IFN)
LT β-glucan
Tumor Cell
T cell receptor
NK
T. C. Finimundy et al.
1099
tests with aqueous extract of the fruiting body [24], fractions of different molecular weight of polysaccharides
[56], crude extract of polysaccharide (LEP) [57] [58] and exudates obtained from the mycelium (DE) [59]. All
reports have shown antioxidant activity with high phenolic content (Table 2).
5. Antiviral Activities of L. edodes
Recent studies have determined the antiviral activity of extracts from LEP on the replication of poliovirus type 1
(PV-1) and bovine herpes virus type 1 (BoHV-1) and the results were anti-virus activity in promoting [60].
The isolated compound lentinan suppressed the activity of HIV-1 reverse transcriptase. In combination with
antiretroviral 3'-azido-3'-deoxythymidine (AZT) lentinan suppressed the in vitro expression of surface antigens
of HIV more efficiently compared to AZT monotherapy. It was also shown that it can increase the in vitro anti-
retroviral effect on HIV replication [61].
Tochikura et al. [62] tested many substances using non-sulfated polysaccharides (EP-LEM) and achieved in-
hibition for HIV-1, HIV-2 and HTLV-1. In another study, various fractions of LEM caused inhibition of infec-
tivity and cytopathic effect of HIV [63] [64]. The mechanism of action is unclear, but it suggests that it may be
related to activation of macrophages and stimulation of IL-1 [9]. A list of different extracts and its anti-viral ac-
tivity is shown in Table 3.
Tumor Cell
TNF-R
MHC-1
β-glucan
TNF-R
activated
Apoptosis
Caspase-8
NF-κB
Figure 4. Direct action for induction of apoptosis and increased
expression of MHC-1.
Table 2. Positive response against tumor cell line using different extracts of L. edodes.
Extract Cell line Reference
Low temperature aqueous total extract Hep-2, HeLa in vitro [24]
Isolated Lentinan FBL-3 erythroleukemia cells [81]
Methanol aqueous total extract In vitro cell line MCF-7 [51]
Mycelia-oral ingestion Mouse (Colon-26) [82]
Mycelia-oral ingestion Mouse (B16 melanoma) [83]
Isolated α-(1,4) glucans A549 in vitro [28]
Ethyl acetate fraction MDA-MB-453, MCF-7, MCF-10F, RPMI-8226, IM-9 in vitro [84]
T. C. Finimundy et al.
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Table 3. L. edodes mycelia extracts and anti-viral activity.
Extract Microorganism References
Isolated lentinan derivate sulphated West Nile virus [10]
Hot water total extract
Ethanolic total extract
Poliovirus type 1 (PV-1) [60]
Isolated polysaccharide Bovine Herpes virus type 1 (BoHV-1) [63]
Isolated lentinan
Isolated laccase HIV-1 [64] [85]
Polysaccharide sulphated
Polysaccharide nonsulfated HIV-2 [61] [62]
Glycyrrhizin sulphated Lentinan sulphated HTLV-1 [62]
6. Antimicrobial Activities of L. edodes
It has been reported that extracts of shiitake possess antibacterial activity enhancing host immunity against in-
fections [34] [50] [64] [65]. Hatvani [63] used solvents like chloroform and ethyl acetate in dried mushroom and
demonstrated bactericidal activity. Lenthionine, a cyclic organosulfur compound partially responsible for the
taste of shiitake showed inhibitory effects against Staphylococcus aureus, Bacillus subtilis and Escherichia coli.
Several studies have shown the ability of the extract of L. edodes to inhibit oral pathogens, mainly causing cavi-
ties and gingivitis [66]-[70].
According to Spratt et al. [71], the fraction of low molecular weight (LMM) isolated from the aqueous extract
of L. edodes also has potential activity against oral pathogens in vitro. A list of different extracts and its antimi-
crobial activity is shown in Table 4.
7. Other Biological Activities of L. edodes
The hypoglycemic effect of an exo-polymer produced from a submerged culture of the L. edodes mycelium was
investigated in rats with induced diabetes, and obtained a reduction in plasma glucose level compared to the
control group. The reduction of cholesterol and triglyceride was also observed [72]. In a study by Akamatsu et
al. [73], fractions obtained from aqueous extraction of L. edodes was examined for its hepatoprotective effect in
injured rats. The reduced levels of aspartate aminotransferase and alanine aminotransferase in the blood were
observed. These hepatoprotective effects are explained by the presence of polyphenols contained in fractions [72]
[74] [75]. Polyphenols contained in both fractions are considered to be potential candidates for expressing the
hepatoprotective effects [35] [76].
Cardiovascular disease is the leading cause of cholesterol levels in the blood throughout the world and is an
important risk factor for the high mortality, therefore hypocholesteremic effects are of great importance. The
ability of shiitake in lowering sanguine cholesterol was first reported in the 1960s [12]. To date, some studies
demonstrate the ability of L. edodes in both decrease very low density lipoproteins (VLDL) as well as high den-
sity lipoproteins (HDL), preventing the increase of blood pressure [45] [77].
The consensus is that regular consumption of fruits and vegetables reduce the risk of cardiovascular disease
(CVD). This is due to the antioxidant activity and immunomodulation exerted by these class of food [78]. Evi-
dence also shows that mushrooms may protect against chronic disease like CVD. Oxidative stress and inflam-
mation are closely linked to atherogenesis [68]. The mechanism of action is due to a significant reduction in
binding of quiescent monocytes and also stimulated by cytokines [78] [79].
The main active component isolated from L. edodes associated to this function is the eritadenine. It reduces
the lipid components of serum lipoproteins both in animals and in humans [80]. According to Isoda et al. [44],
the oral administration of this compound proved to be effective and demonstrate low toxicity, although only
10% is absorbed in the gastrointestinal. As intravenous administration, it proved completely ineffective, and
quickly eliminated from circulation and excreted by the kidneys.
8. Conclusion
The L. edodes is a macrofungus, that presents a variety of nutrition compounds, with great potential for thera-
peutic application. The activity and use of this macrofungus are unquestionable in some of the most important
T. C. Finimundy et al.
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Table 4. L. edodes extracts against antimicrobial activity.
Extract Microorganism References
Low molecular weight Actinomyces naeslundii [69] [86]
Dry aqueous extract total Bacillus cereus [65]
Dry aqueous extract total Bacillus subtilis [65] [87]
Dry aqueous extract total Enterococcus faecalis [65]
Isolated liquid medium Listeria monocytogenes [87]
Dry aqueous extract total Staphylococcus aureus [65]
Dry aqueous extract total MRSA [65]
Low molecular weight Fusobacterium nucleatum [86] [69]
Isolated liquid medium Klebsiella pneumoniae [87]
Isolated liquid medium Proteus mirabilis [87]
Ethanol extract total and dry aqueous Pseudomonas aeruginosa [65]
Low molecular weight Yersinia enterecolitica [86]
areas of applied biotechnology. Medicinal value of mushroom intake has become a matter of great significance,
particularly in preventing or treating serious chronic conditions such as cancer and cardiovascular disease. From
a pharmacological point of view, safety is the primary issue and research in this direction is desired. To date, L.
edodes has shown to present a great potential for the production of useful bioactive metabolites that serve as a
rich resource for drugs. Further research however is needed to establish content and bioactivity of the many
compounds found in edible mushrooms.
Acknowledgements
This work was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
(CAPES) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).
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