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Ganodermataceae: Natural Products and Their

Related Pharmacological Functions

Xuanwei Zhou,* Juan Lin, Yizhou Yin, Jingya Zhao,*

Xiaofen Sun and Kexuan Tang*

*Plant Biotechnology Research Center, School of Agriculture and BiologyState Key Laboratory of Genetic Engineering, School of Life Sciences

Fudan-SJTU-Nottingham Plant Biotechnology R&D Center

Fudan University, Shanghai 20030, China

Abstract: The objective of this paper is to review the natural products and the pharmacological

functions ofGanodermataceae family. Presently, studies on the bioactive components of

Lingzhi are focused on polysaccharides and triterpenes/triterpenoids compounds. New

Ganoderma polysaccharides, including their molecular weights, glycosyl residue compositions,

glycosyl linkage and branches, are summarized in this paper. Also presented are new types of

triterpenes and their characteristics from Lingzhi. Taking Ganoderma lucidum as an example,

we reviewed its pharmacological functions in anti-tumor and immune-modulating activities

for treating hypoglycemosis, hepatoprotection, and the effect on blood vessel system. Based

on the advances in Lingzhiresearchin the past few decades, both G. lucidum and G. sinense

are considered as the representative species of medicinal mushroom Lingzhiin China. Until

2001, G. tsugae was only advised to be used as the materials of the health products. The

biologically-active components related to pharmacological functions of these three species

were studied more than other Ganodermataceae family species; however, which have been

used in less modern folk medicine.

Keywords: Ganoderma; Polysaccharides; Triterpenoids; Pharmacology.

Introduction

Ganoderma is a genus of wood decaying polypore fungi of economic importance. It is

named as Reishi in Japan, Ganoderma in US, and Lingzhi in China. Several species

compose the raw materials used for synthesis of human health products. In China, Lingzhi

is regarded as an herb of longevity and has been used by humans for thousands of years,

and strains have been commercially cultivated for the preparation of health products

Correspondence to: Dr. Xuanwei Zhouor Dr. Kexuan Tang, Plant Biotechnology Research Center, School of

Agriculture and Biology, Fudan-SJTU-Nottingham Plant Biotechnology R&D Center, Shanghai Jiao Tong University,

Shanghai 200030. Tel: (+86) 21-6293-2002, Fax: (+86) 21-6564-3552, Email: [email protected]

or [email protected]

The American Journal of Chinese Medicine, Vol. 35, No. 4, 559574

2007 World Scientific Publishing Company

Institute for Advanced Research in Asian Science and Medicine

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since 1970s. Lingzhi is ranked as rare and precious in the ancient Chinese medical

encyclopedias Shen Nongs Ben Cao Jing, and Ben Cao Gang Mu written by Li Shi-

zhen, a famous herbal scholar in the Ming Dynasty. Up to now, traditional medicineshave held an important status in health care systems in developing countries, and Lingzhi

has been one of the most prescribed traditional medicines. Today, the largest users of

traditional medicines are Chinese. Among the 98 genus distributed throughout China,

there are two species, Ganoderma lucidum (Leyss. ex Fr.) Karst. and G. sinense Zhao, Xu

et Zhang, which are written in pharmacopoeia of China in 2005 (Chinese Pharmacopoeia

Committee, 2005). One species, G. tsugae Murr, was regarded for its use in health products

(Chen et al., 2004). However, white rot fungi are believed to be themost effective materials

of health products derived from fungal microbes. Previous studies have focused on the

investigation of resources (Jia et al., 2003), analysis of the nutritional components (Zhou

et al., 1998), and cultivation of fresh body and preparation of health products (Wanget al., 1999). Recently, there has been an increasing interest instudying the relation between

the structure and function of active components. Most are focused on polysaccharides

and triterpenoids compounds, which are considered as new active compounds, and their

pharmacological functions.

Lingzhi is the most important and widely distributedwhite rot fungi of a wide variety

of hardwoods and commonly used as health products (Wu et al., 2004). Resent studies

have concentrated on the medicinal properties of these fungi (Deng et al., 2005). Except

for two compounds (polysaccharide and ganoderic acid), little is known about lectin and

other medicinal proteins from Lingzhi. In this report, we describe the productsof various

biotechnological applications under different culturing conditions, with emphasis on its

valuable bioactive compounds which include not only ganoderic acid and polysaccharides,

but also proteins and other metabolites.

Natural Products

Lingzhi contains numerous bioactive natural components (e.g., polysaccharides, ganoderic

acids, ergosterols, proteins, unsaturated fatty acids, vitamins and minerals) (Niu et al.,

2002), which contain properties conducive for normalizing and balancing the body,

and as a result, they can enhance health and aid in relief of a multitude of diseases.Lingzhi extracts have preventive and curative effects on diseases such as: heart disease,

hypertension, hepatitis, diabetes, neurasthenia, tumor and cancer. It has also been reported

that some components have inhibitory effects on the growth of human immunodeficiency

virus (HIV) (el-Mekkawy et al., 1998). It is expected that future investigations will lead

to finding other roles of Lingzhi in prevention and treatment of diseases that affect human

health.

Polysaccharides

Polysaccharides, usually extracted from Lingzhi using the water extract and alcohol

precipitating method, are the most important components, and represent a class of

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structurally-diverse biological macromolecules with wide-ranging physiochemical

properties (Chen et al., 1998; Bao et al., 2001a). The importance of polysaccharides

(including protein/peptide bound polysaccharides) in pharmaceuticals has a long history,and has received considerable attention in recent years (Lin et al., 2005). Research on the

anti-tumor and immune-modulating activities of medicinal mushrooms, including Lingzhi,

had been reported as early as in 1960s, and recent extensive studies on the anti-tumor

ingredient(s) contained in these fungi, especially polysaccharides and protein-conjugated

polysaccharides have been conducted (Chen et al., 2005a).

For many years, Ganoderma polysaccharides (Ganopoly) had been the emphasis in

Lingzhi research. More than 200 polysaccharides have been isolated from the fruiting

bodies, spores, mycelia and cultivation broth of Lingzhi (Bao et al., 2002a; Bao et al., 2001b;

Peng et al., 2005a; Peng et al., 2005b). The major bioactive polysaccharides isolated from

Ganoderma species are glucans, -1-3 and -1-6 D-glucans. Ganopoly mainly consists ofneutral polysaccharides of glucose units; about one third of the polysaccharides consist of

(13)--D-glucan containing -(16)-D-glucosyl branches. Previous literature reported

that most of the anti-tumor glucans contained a branched glucan core with (13)--,

(14)-- and/or (16)--linkages and have an average molecular weight of 1,050 kDa

(Bao et al., 2001a and b).

However, there are significantly different amount of bioactive (13)--D-glucan

polysaccharide contents present in the fruiting bodies obtained by using solid culture

method and the fermentation broth obtained by liquid fermentation method. These

differences are caused by the variations in fungal strains and in the culture methods(Zhang

and Zhang, 2005). Additionally, the molecular weight of the active polysaccharides varies

by the different extraction methods and materials (such as mycelia, fruiting bodies or

spore power). It is clear that there are qualitative and quantitative differences in active

polysaccharides obtained from fruiting bodies and products of liquid fermentation. The

methods for polysaccharide extraction, isolation and purification are described in the

literature (Huie et al., 2004). The chemical characteristics of the most recent studies on

Ganopoly are summarized in Table 1.

Triterpenes/Triterpenoids

Triterpenes/triterpenoids is one of the most important biologically active components of

Lingzhi. The groups of triterpenes have received considerable attention because of their

well-known pharmacological activities. Since the first isolation of two new triterpenes,

ganoderic acids A and B, from the dried epidermis ofG. lucidum by Kubota et al. (1982),

more than 130 oxygenated triterpenes (mostly lanostane-type triterpenes) have been isolated

from the fruiting bodies, spores, mycelia and culture media of Lingzhi (Huie et al., 2004).

These triterpenes could be divided into the C30, C27 and C24 compounds according to the

number of carbon atoms and based on the structure and the functional groups (Gao et al.,

2005a; Luo and Lin, 2002). In general, triterpenoids have molecular weights ranging from

400~600 kDa and their chemical structures are more complex than the group of lanostanesbecause of their highly oxidized state.

PHARMACOLOGICAL FUNCTIONS OF NATURAL PRODUCTS FROM GANODERMA

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Table1.

NewGanopolyanditsPhysicalandChemicalCharacteristics

No.

Name

Molecular

Weight

Glycosyl

ResidueCompositions

(M

olarratioofca.)

GlycosylL

inkageandBranches(Characteristic

Signals)

Source

Ref.

1

/

/

nGlu:nFru=7:1

/

Fruitingbody

Che

netal.,

2001

2

/

/

nGlu:nFru=7:1

/

Mycelia

3

/

/

N

Glu:nFru=2:1

/

Fermentationliquid

4

PL-1

8.3

103

nRha:nGal:nGlc=1:4:13

PL-1glucanpossessedabackbonecomposedof1

,4-

linked-g

lucopyranosylresidueswithbranching

points

atO-4ofglucosesidechainsandgalactosesidechains.

Fruitingbody

Baoetal.,

2

002a

5

PL-3

6.3

104

Glu

PL-3glucanpossessedabackbonecomposedof1

,3-

linked-D

-glucopyranosylresidueswithbranchin

g

pointsatO

-6ofglucosylresidueswith1,6-linked

-D-

glucosesidechains.

Fruitingbody

6

PL-4

2.0

105

nMan:nGlu=1:13

Consisted

ofaprimarystructureof1,3-,and1,4-

linked-D

-glucopyranosylresiduesand1,6-linked

-D-mann

opyranosylresidueswithbranchesatO

-6

ofglucosy

lresiduescomposedof1,6-linked-D-

glucopyranosylresidues.

Fruitingbody

7

/

4.2

104

nGlu:nGal

:nMan:nXyl:nAra:nRha=

5.82:2.23

:1.00:1.35:0.72:0.51

Consisted

ofaprimarystructureof1,3-linked-D

-

glucopyranosylresidues,withbranchingpointsat

O-6

andO-4.

Fruitingbody

Luoetal.,

1998

8

/

3.7

104

nGlu:nGal

:nMan:nXyl:nFuc:nRha=

5.35:2.67

:1.00:1.19:0.38:0.37

Consisted

ofaprimarystructureof1,3-linked-D

-

glucopyranosylresidues,withbranchingpointsat

O-6

andO-4.

Mycelia

9

GLIS

/

nGlu:nGal:nMan=3.0:1:1

/

Fruitingbody

Zhangetal.,

2002

10

GLPG

5.13105

nRha:nXyl:nFru:nGlu=0.549:

3.614

:3.167:0.556:6.89

Mainlyco

nsistedof-D-glucopyranosylresidues,and

alsoafew

-D-glucopyranosylresidues.

Fruitingbody

Lin

etal.,

2003

11

GLPW

5.85105

nRha:nXyl

:nFru:nGal:nMan:nGlu=

0.793:0.964

:2.944:0.167:0.387:7.94

Mainlyco

nsistedof-D-glucopyranosylresidues,and

alsoafew

-D-glucopyranosylresidues.

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Table1.

(Continued)

No.

Name

Molecular

Weight

Glycosyl

ResidueCompositions

(M

olarratioofca.)

GlycosylL

inkageandBranches(Characteristic

Signals)

Source

Ref.

12

SeGLP-1

/

nGlu:nMan:nXyl:nGal:nRha=

0.23:1

.00:0.72:0.25:0.09

Abackboneof-D-glucopyranosylresidues.

Mycelia

An

etal.,

2001

13

SeGLP-2

/

nXyl:nGal:nGlu:nRha=

1.63

:25.59:1.00:0.86


Mycelia

14

LB-NB

4.7

104

Glu

Abackboneof-(13)-linkedD-glucopyranosyl

residues,linkedwithsingleterminalglucosylresidueat

theC-6of

every4.4glucosylresiduesinthemain

chain

Spore

Baoetal.,

2000

15

SP

1.0

104

D-Glu


residues,withbranchesofmono-,di-andoligosaccharide

sidechain

ssubstitutingattheC-6ofglucosylresiduesin

themainc

hain.

Spore

Baoetal.,

2

001b

16

/

1.26105

D-Glu


residues,withbranchesofmono-,di-andtrisacch

aride

sidechain

ssubstitutingattheC-3orC-4ofglucosyl

residuesinthemainchain.

Spore

Baoetal.,

2

001a

17

PSGL

/

D-Glu


residues,linkedwithsingleterminalglucosylresidueat

theC-6of

glucosylresiduesinthemainchain.

Spore

Baoetal.,

2

002b

18

GLPL1

0.41104

Glu


Fruitingbody

Zha

oetal.,

2003

19

GLPL3

0.41105

Glu+Gal


Fruitingbody

20

SGL--2

5.37104

nGlu:nGal=12.31:1


residues,with1,4-linked-D-galactosesidechain

s.

Spores

Zha

oetal.,

2005

21

Lzps-1

0.8

104

Glu


residues,with1,6-linked-D-glucosesidechains.

Spores

Jian

getal.,

2005


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These fat-soluble components in Lingzhi were heavily studied during the 1980s. Up

to 2000, the total of triterpene compounds were summarized to 112 kinds and represented

24 structures (Lin, 2001). Currently, about 136 triterpene structures have been isolated (Liet al., 2005)and these are listed in Table 2 (Gao et al., 2005a).

Bioactive Components

Protein, Peptides and Amino Acids

Several active proteins have been isolated from Lingzhi, while some other proteins

exist in the polysaccharide-peptide complex. In early 1989, a novel protein was isolated

from the mycelial extract of G. lucidium (Kino et al., 1989; Tanaka et al., 1989). The

protein was named ling zhi-8 (LZ-8) and its complete amino acid sequence, biochemicaland immunological properties have been described (Miyasaka et al., 1992). The LZ-8

was shown to be mitogenic toward mouse splenocytes in vitro and immune-modulating

in vivo by reducing antigen-induced antibody formation and by completely preventing the

incidence of autoimmune diabetes in non-obese diabetic mice. In addition, an antifungal

protein(Wang etal., 2006) and other biologically active proteins (Ngai et al., 2004; Tian

and Zhang, 2005) have also been isolated from Lingzhi.

In many plant and animal materials, bioactive peptides (BAP), defined as peptides with

molecular masses < 6 kDa, have been found to possess antioxidant properties. Whereas,

research has shown that the Lingzhi peptide is the major antioxidant component. Up till

now, there have been a few bioactive peptides isolated from the water-soluble fraction of

G. lucidum (Sun et al., 2004). Moreover, in a previous study, the various amino acids, which

are necessary for human body and have a high nutritional value and medicinal properties,

had been reported. In general, the contents of the aspartic acid, glutamic acid, alanine and

leucine from mycelia, fruiting body and spore powder were higher than other amino acids.

The contents of amino acid are different in various Ganoderma species(Zhang and Zhang,

1996).

Other Active Compounds

In recent years, there has been interest in the cholesterol lowering properties of the

mushrooms. Since then, cholesterol has been isolated from ethanol extraction ofG. lucidum

followed by column chromatography for the first time. The compound was characterized

as 24-methyl- cholest-5, 22-dien-3-ol by spectroscopy (Wang et al., 2005). Hajjaj et al.

(2005) have reported the isolation and identification of the 26-oxygenosterols ganoderolA,

ganoderol B, ganoderal A, and ganoderic acid Y and theirbiological effects on cholesterol

synthesis in a human hepaticcell line in vitro. Meanwhile, steroids such as 5-ergosta-7,

22-dien-3-ol or 5,8-epidioxy-5, 8-ergosta-6, 22-dien-3-ol were also isolated from

G. applanatum and proved to be weakly active against many gram-positive and gram-

negative microorganisms (Lindequist et al., 2005). On the other hand, well-known anti-microbial compounds were also isolated from Lingzhi, such as applanoxidic acid A,

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Table2.NewTriterpenesoftheG.

lucidum

*

No

.

Name

MolecularFormula

Types

mp/C

[]D

Source

Ref.

1

LucidendicacidO

C27H38O7

L

ucidunicacid

/

+71

Fruitingbody

Mizushinaeta

l.,1999

2

Lucideniclactone

C27H40O7

Ganolactone

/

+13

Fruitingbody

3

LucidenicacidP

C29H42O8

L

ucidunicacid

135137

14.7

Fruitingbody

Iwatsukietal.,2003

4

MethyllucidenatesP

C30H44O8

Methyllucidenates

8385

77.6

Fruitingbody

5

MethyllucidenatesQ

C28H46O6

Methyllucidenates

130131

58.5

Fruitingbody

6

8,9-dihydroganodericacid

J

C30H44O7

G

anodericacid

205208

24

Fruitingbody

Maetal.,2002

7

Methly8,9-dihydroganodericacidJ

C31H46O7

Me

thyllucidenate

202205

52

Fruitingbody

8

20-hydroxylganodericacidG

C30H44O9

G

anodericacid

175177

42

Fruitingbody

9

LucidenicacidN

C27H40O5

L

ucidenicacid

202204

119.5

Fruitingbody

Wuetal.,2001

10

MethyllucidenateF

C28H38O6

Me

thyllucidenate

205207

120.0

Fruitingbody

11

CompoundVI

C28H8O8

L

ucidenicacid

185186

96

Fruitingbody

Luoetal.,

2002

12

CompoundVII

C31H44O9

L

ucidenicacid

196197

108

Fruitingbody

13

LucidenicacidLM1

C27H40O6

L

ucidenicacid

130131

140

Fruitingbody

Luoetal.,2001

14

GanodericacidLM2

C30H42O7

G

anodericacid

228230

132

Fruitingbody

LuoandZhao,2002

15

Ganodericacid

C30H44O7

G

anodericacid

243245

155.3

Spores

Minetal.,2000

16

Ganodericacid

C30H44O7

G

anodericacid

/

160.0

Spores

17

Ganodericacid

C30H44O7

G

anodericacid

249251

153.3

Spores

18

Ganodericacid

C30H42O7

G

anodericacid

143145

213.3

Spores

19

Ganodericacid

C30H44O8

G

anodericacid

212214

128.0

Spores

20

Ganodericacid

C30H42O8

G

anodericacid

131133

71.3

Spores

21

LucialdehydeA

C30H46O2

L

ucialdehyde

/

32.2

Fruitingbody

Gaoetal.,2002

22

LucialdehydeB

C30H44O3

L

ucialdehyde

/

32.2

Fruitingbody

23

LucialdehydeC

C30H46O3

L

ucialdehyde

/

18

Fruitingbody

24

GanodericacidSz

/

G

anodericacid

/

Fruitingbody

Lietal.,2

005

*Revisedfromreference:Gaoetal.,2005a.


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isolated from G. annulare, showed weak antifungal bioactivity against Trichophyton

mentagrophytes (Smania et al., 2003).

Pharmacological Functions

The extracts from the spore, mycelium and fruit bodies of Lingzhi have long been

considered for good health. It can help enhance bodys immune system and improve

metabolic functions (Lin et al., 2002; Pero et al., 2005). Biological activities and

pharmacological functions reported for Ganoderma species include aspects of various

effects on physiological function of human organs and systems.

Anti-Tumor Effects

Tumor diseases are one ofthe main causes of death in the world. The inhibition of growth

of differenttumors was detected in about200species of Lingzhi.Ganoderma species and

its extracts have been known as a traditionalremedy, used in traditionalChinese medicine

forprevention and treatment ofcancer and several other diseases(Yang et al., 2005).

It is generally accepted that the antitumor and anticancer effects ofpolysaccharides

arise from the enhancement of the bodys immune system rather than direct cytocidal

effects(Lin et al., 2002). There is evidence that-D-glucans induce a biologicalresponse

by binding to membrane complement receptor type 3 on immune effectors cells. The

ligand-receptor complex can be internalized. The intercellular events that occur afterglucan-receptorbinding have notbeen fully determined untill now (Zhou and Gao, 2002).

The antitumourpolysaccharides differ greatly in theirsugarcomposition and consequently

in chemicalstructure, but one common feature istheirrelatively high molecular weight.

It hasbeen reported thatpolyglucans with a highermolecular weight(1046Da)tend to

have greater watersolubility and therefore have a more effective antitumour activity.For

example, Zjawiony (2004)regarded that higher anti-tumor activity of-glucansseemsto

be correlated with highermolecular weight, lower level ofbranching and greater water

solubility.Based on the results ofmodern scientificresearch, molecular weight, degree of

branching, number ofsubstituents, aswell as ultrastructure, including the presence ofsingle

and triple helices, significantly affectthe biological activities of-glucans(Adachi et al.,2002).Anti-tumor activity and underlyingmechanisms ofthe Ganopoly had been explored

in mice. The overallfindings indicated thatGanopoly showed antitumor activities with a

board spectrum of immuno-modulation activities and may represent a novelpromising

immunotherapeutic agent in cancertreatment(Gao et al., 2005b).

Immune-Modulating Activities

The bodys immune systems are the defense systemthatkeep a person healthy and protect

ourbodies against infections and illnesses. The immune systemsconsist of immune organs

which include the thymus, bonemarrow, spleen, lymph node, etc.The immunocyte includesbyUNIVERSIDADAUTONOMADEL




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thymus dependentlymphocyte (T cell), bursa-dependentlymphocyte (Bcell), naturalkiller

cell, and K cell.Millions ofthe immune cytokines including the interleukins, interferons

and variousstimulating factors are also the members ofthe immune systems. The currentpractice of ingesting phytochemicalsto supportthe immune system orto fight infections

isbased on the centuries old tradition (Tan and Vanitha, 2004).An aqueousGanopoly

hasbeen marketed as an over-the-counterproduct forchronic diseases including cancer

and hepatopathy in many Asian countries.Materials in different developing stages (e.g.

the mycelia, the fruiting body and the spore power orthe water-extraction oftheirs)can

provide different effect on immune enhancement, immunosuppression and immunological

recovery.In these studies, more investigationsstartto focus on the Ganopoly, especially

its effects on the immunocyte and immunological activities(Hao and Li, 2004; Kuo et al.,

2006).As a biological immune-modulator, Ganopoly affects the bodys immune system

through the following pathways:(1)By activating macrophage, Ganopoly facilitates theT-lymphocytestransferring to cytotoxic T cells, enhancesthe number and activity ofthe

B-lymphocytes and the naturalkillercells.(2)Ganopoly can activate the reticuloendothelial

system and the complementsystem; induce the various immune factors, such asINF, TNF

and so on.(3)Itmay influence the Nerve Endocrine Immune System.(4)Ganopoly can

facilitate the RNA, DNA and protein synthesis in cells, enhance the contents ofthe cGMP

and cAMP in cells as well(Habijani et al., 2001).

In orderto prove the immune-modulator effect of Lingzhi, Chinese scientists didmany

experiments.For example, Chen et al.(2004)reported the identification of a glycoprotein

fraction, isolated from the water-soluble extract of G. lucidum, that can stimulate

spleen cellproliferation and cytokine expression. Subsequently they carried out further

purification of the active fraction to enrich the immune-modulating activity, as well as

the detailed analysis of cytokine expression, especially that of GM-CSF and IFN-c.

Apart from glycoprotein, the polypeptides fromGanoderma species were also bioactive

compounds on immune enhancement. Lentinan fromG. lucidum are used in clinics(i.e.

0.51.0mg lentinan per day, intravenous), especially in China, for the adjuvant tumor

therapy (immunotherapy) in addition to the majorcancertherapieslike surgical operation,

radiotherapy and chemotherapy(Tan andVanitha, 2004).

Hypoglycemic Treatment

Hypoglycemia is an abnormal glucose metabolicphenomenon caused by many factors,

which could cause the patientsto have a low level ofblood glucose (

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treated with Ganopoly (1800mg three times daily for12 weeks). The mean post-prandial

glucose values had decreased to 11.8mM after12 weeks oftreatment(Gao et al.,2004).

The mechanism ofGanopoly for the treatment of diabetes was studied. The resultsshowed thatGanopoly promoted insulin release when the glucose level was between

5.6mM and 16.7mM due to the promotion of the GLUT2protein expression and the

subsequent facilitation ofCa2+ inflow into the pancreaticBcells(Zhang and Lin, 2003).

Actually, the substancesplaying a role in hypoglycemic treatment were not glycansbut

peptidoglycans.

Hepatoprotection

Lingzhi and its extracts can prevent liver damage induced by alcohol, and also have a

certain protective action for liver damage induced by CCl4 and D-GalN in rats (Chen

et al., 2001;Liu et al., 2000). Studies on the effects oftriterpenoids isolated fromG. lucidum

on immunologicalliver injury model in mice in vivo, indicated thatthe triterpenoids had

significant protective effects against immunological liver damage induced by bacille

calmette-guerin (BCG)plus lipopolysaccharide (LPS) in mice both in vivo and in vitro

(Wang and Lin, 2000).

Preceding research proved that the extracts from G. lucidum show in vitro anti-

hepatotoxic activity in the galactosamine-induced cytotoxic test with primary cultured

rat hepatocytes.In vivo, two fractions of a total triterpenoids extract of G. lucidum

(75% ethanol) can protectmice against hepatic necrosis induced by chloroform and

D-galactosamine. The hepatoprotective effects were perhaps related to the ability to

promote the activity ofscavenging enzymes for hepatic free radicals in mice, and thus

to raise the ability of antioxidation in mice (Lin et al., 2002).In another aspect, Chinese

doctorsproved thatthe polysaccharide-containing preparation ofG. lucidum had curative

effect on patients with chronic hepatitis B. Following treatment with Ganopoly for

6months, the aminotransferase levels of33%patients(17/52)return to normalvalues, 13%

patients(7/52) had cleared hepatitisBsurface antigen fromserum, whereas none ofthe

controls had normal enzyme values or had lostHBsAg. The drug was well-tolerated (Gao

et al., 2002).Itreported thatthe triterpene extracts from G. lucidum had anti-tumor effects

by inhibiting growth of hepatoma cells via suppression ofprotein kinase C, activatingmitogen-activated protein kinases and G2-phase cellcycle arresting, and then preventing

cell growth of human liver(Lin et al., 2003).

Effects and Mechanism on Cardiovascular System

Reactive oxygen species and increased levels of blood lipids are key elements in the

pathogenesis of atherosclerosis, one of the main causes of death in industrialcountries.

The control ofblood lipids, especially cholesterol, is important forreducing the risk of

the development orprogression of atherosclerosis.Chen et al. (2005a) investigated the

effect ofGanopoly on blood lipid and lipoperoxidation in the experimental hyperlipidemicbyUNIVERSIDADAUTONOMADEL




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rats, the results showed that Ganopoly can regulate lipid metabolism, enhance the

antioxidation and reduce the lipid peroxidation in the rats with hyperlipidemia.In order

to explore the therapeutic mechanism for atherosclerosis, the effect of Ganodermalucidum on counteracting lipid peroxidation in cultured vascular smooth muscle cell

(VSMC) was investigated, the results indicated that lingzhi can counteract the lipid

peroxidation in VSMC and itstherapeuticmechanism for atherosclerosismay be related

to the counteraction of lipid peroxidation and enhancement of endogenous antioxidase

activity (Du et al., 2003). Other reports had previously indicated that triterpenoids

isolated fromG. lucidum possessed the ability to inhibit the biosynthesis ofcholesterol,

and contributed to atherosclerosis protection by inhibition of angiotensin converting

enzyme or ofplatelet aggregation. The difference ofGanopoly and triterpenoids affecting

the cardiovascularsystem, and their acting mechanism had been demonstrated by many

experiments(Lindequistet al., 2005; Lin, 2004;Du et al., 2003; Zhang et al., 2001; Luoet al., 2005).

Lingzhi may affectcholesterol synthesis (Frye and Leonard, 1999); the oxygenated

sterols from G. lucidum can inhibit cholesterol biosynthesis via conversion of acetate

ormevalonate as a precursor ofcholesterol(Hajjajet al., 2005). Some triterpenes from

G. lucidum, such as ganoderic acid F, contribute to atherosclerosisprotection by inhibition

of angiotensin converting enzyme or ofplatelet aggregation (Su et al., 1999).

Apart from previously mentioned pharmacological functions, by the folk ofChina,

Lingzhi is used in the treatment of fatigue, coughing, asthma, insomnia, indigestion,

hypertension, high cholesterol and neurosis.Itcan also reduce the side effects and pain

during chemotherapy and radiotherapy forcancerpatients.However, it also can cleanse the

blood, detoxify and regulate endocrine function, and helppromote longevity and strengthen

health. The scientists have confirmed and proved the effectiveness of Lingzhi.

Conclusions

The family of Ganodermataceae consists of a large group of tree fungi of the class

Polyporaceae, specifically the genus Ganoderma and other related genera. The typical

species of Lingzhi isG. lucidum (Fr.) Karst. Lingzhi hasbeen considered an extremely

valuable Chinese herbalmedicine since ancienttimes.Uptill now, more than 100 Lingzhispecies are distributed all overthe world, about98species have been reported in China,

and among them only 18species are being studied. The number ofspeciesthat have been

commercially cultivated were only 23species(Chen and Li, 2004).Only very few species

have been subjected to systematicpharmacological tests and clinical applications, while

many are yetto be studied further.

The bioactive components of Lingzhi include polysaccharides, triterpenoids, low

molecular weightproteins, and sterols, etc., which are health productsmaterialsthat have

been verified by many scientificreports.Except for a few molecularmechanisms oftheir

pharmacological functions, most are notcompletely clear. There are much differences in

methodology between Eastern and Western medicine.Unlike Western medicine in whichtherapeutic effects are usually derived from a single chemicalsubstance in the drugs, the

PHARMACOLOGICAL FUNCTIONS OFNATURAL PRODUCTS FROMGANODERMA

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pharmacological activities of herbalmedicine invariably arise from a mixture ofactive

ingredients in the herbalmaterials (Huie, 2002).Although the resources are abundant

in China, very few Lingzhi species are cultivated and used as human health products.In future, Chinese scientistsshould enhance to study the development and utilization of

more Lingzhi resources, breed a few new species which have a differentcurative effect

(ormedicinalcomponents and contents), attach importance to the molecularmechanisms

ofpharmacological functions, and conform to internationalmedicinalmaterialsmarket

requirement.

In developing countries, including those in Asia,Africa and mostAfrican Union (AU)

states, traditionalmedicines are importantbut often unacknowledged ascomponents ofthe

health care system.Pharmaceuticalchemists in these countries are well equipped to bridge

the gapbetween traditional and western allopathicmedical systems (Springfield et al.,

2005). The application ofstandard pharmaceuticalmethodsto the quality assurance, safetyassessment and efficacy testing of Lingzhiconstitutesthefirststep in the process ofbringing

them fromthe field into the clinic, dispensary and hospital.Although traditionalmedicines,

including Lingzhi, were not accepted inmany countries ofthe world, we believe that itwill

play an importantrole in human health care in the near future, since intercommunion and

cooperation activities are enhanced in areas ofscience and technology.

Acknowledgments

This research isfinancially supported by Shanghai Science and Technology Committee

(No.05dz05007) and School ofAgriculture and Biology, Shanghai Jiao Tong University.

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