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17(1): 01-12, 2022
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MEDICINAL EFFICACY OF EDIBLE MACRO FUNGUS Ganoderma


applanatum (PERS.) PA
(PERS.) T. – A REVIEW
PAT

SUKUMAR DANDAPAT1*, MANOJ KUMAR2, ROHIT SRIVASTAVA1 AND MANORANJAN PRASAD SINHA1
1
Department of Zoology, Ranchi University, Ranchi-834008, Jharkhand, INDIA
2
Department of Zoology, St. Xavier’s College, Ranchi-834001, Jharkhand, INDIA
e-mail: dr.sukumar2018@gmail.com

KEYWORDS ABSTRACT
Biochemical Disease Medicinal mushrooms are used in traditional medication. They are easily available and cost effective source for
Ganoderma the people of rural and tribal areas. In the present review, an attempt has been made to congregate the taxonomic,
applanatum Medicine mycochemical and pharmacological studies done on an important medicinal mushroomGanoderma applanatum.
Mushroom Extensive experimental studies prove that Ganoderma applanatum possesses antibacterial, antifungal, antiviral,
antioxidant, anticancer, anticholestromic, antidiabetic, nephroprotective, hepatoprotective, hypouricemic,
Received on : immunostimulatory properties, which help it to play role in prevention and treatment of many disease. Therefore,
17.09.2021 it is worthwhile to review therapeutic properties of G. applanatum to give an overview of its status to scientist
both modern and ancient.
Accepted on :
25.02.2022

*Corresponding
author

INTRODUCTION ethnic groups has proven to be extensive and profound,


consuming nearly 283 species of wild mushrooms as food
Improper nutrition and modern lifestyle are the two common and medicine out of the 2,000 species (Choudhary et
reasons for the growth of diseases and disorders all over the al.,2015).
world (Kozarski et al., 2015).It has been estimated by the
Mushrooms belonging to genus Ganoderma, commonly
World Health Organization (WHO) that about 80% of the
known as Reishi mushrooms, is the largest genus in the order
earth’s inhabitants rely on traditional medicine for their primary
Polyporales with more than 400 records, are known for their
health care (Krishnaiah et al., 2011). Since beginning of
medicinal importance in the Asian continent. Boundless
mankind nature is the most important source of medicines,
traditional medicinal uses of Ganoderma species have
and the bioactive compounds produced from traditionally
attracted the pharmaceutical industry recently (Loyd
used living organisms have been used directly as drugs or as
et al., 2018). Several studies reported that Ganoderma
lead compounds for drug development.Medicinal mushrooms
applanatum has many medicinal properties such as
have the potentiality to become real drugs of traditional and
antibacterial, antiviral, antitumor, antifibrotic, antiobesity,
evidence-based medicine (Lindequist et al., 2014).
antioxidative, and immunomodulatory (Luo et al., 2017 Gao
The mushrooms have been defined as a potential source of et al., 2019). The goal of the present review is therefore to
dietary fiber, high quality of proteins, essential amino acids, crystalize the knowledge of the effectiveness of Ganoderma
as well as the numerous vitamins and minerals, applanatum as a possible natural oral hypoglycemic,
polysaccharides, glycoproteins, unsaturated fatty acids, hypolipidemic, and hepatoprotective agent, or functional
phenolic compounds, ergosterols, lectins etc. (Gaoxing et food, in reducing hyperglycemia along with other vascular
al.,2018). In recent years innumerable studies have been complications reported by different workers apart from other
focusing on the therapeutic benefits of mushrooms,including aspects of medicinal efficacy of the species.Ganoderma
the immune boosting activity, anticancer, anti-inflammatory, mushrooms are important medicinal mushroom, being used
antioxidant, antifungal, antibacterial, antiviral and many other in clinical, pharmaceutical, and nutritional industries for the
medicinal properties (Rathore et al., 2017; Gaoxing et al., treatment of various diseases such as migraine, hypertension,
2018). asthma, hepatitis, cancer, and cardiovascular problems
It is estimated that nearly 1,40,000 mushroom species are (Mawar et al.,2020).
found all over the world and among them only 5 percent This review covers bioactivities of medicinal mushroom
could profit the mankind. Most edible and certain non-edible, Ganoderma applanatum from different countries of the world.
non-consumptions mushrooms have been recognized to In this context, we aimed to give an overview and
improve health from several thousand years ago (Bell et summarization of the nutritional, therapeutic benefits and other
al.,2022).Traditional mycological knowledge of most Indian bioactivities of G. applanatum in the present review. The

1
SUKUMAR DANDAPAT et al.,

review including the bioactive nutraceuticals in G. applanatum over 2000 years, and its powerful effects have been
and their functioning mechanisms, which could be conducive documented in ancient scripts (Wasser et al.,2005). In
to the better understanding of the correlations between the G. the supplement to Classic of Materia Medica (502-536 AD)
applanatum consumption and health improvement. and the Ben Cao Gang Mu by Li Shin-Zhen, which considered
Taxonomic and medicinal history to be the first pharmacopoeia in China (1590 AD; Ming
dynasty), the mushroom was attributed with therapeutic
The genus Ganoderma was established as genus in 1881 with
properties, such as tonifying effects, enhancing vital energy,
with single species G. lucidum (Curtis:Fr.) P. Karst from England
strengthening cardiac function, increasing memory, and
as the type species by Finnish mycologist Peter Adolf Karsten
antiaging effects (Wachtel-Galor et al.,2011).
and before Karsten this taxon was characterized as Boletus
lucidum by Curtis in 1781 (Karsten, 1881; Palanna et al.,2020). Classification (Anand and Chowdhry, 2013; CABI, 2020)
The mushroom G. applanatum was first reported by German Domain: Eukaryota
mycologist Christiaan Hendrik Persoon who made additions Kingdom: Fungi
to Linnaeus mushroom taxonomy. He gave it the binomial
Phylum: Basidiomycota
scientific name Boletus applanatus and this polypore was
transferred to genus Ganoderma in 1887 by the French Subphylum: Agaricomycotina
mycologist Narcisse Theophilr Patouillard (First Nature, 2021). Class: Agaricomycetes
From ancient time the mushroom of genus Ganoderma has Subclass: Agaricomycetidae
been used as traditional medicinal supplement in some Asian Order: Polyporales
countries such as China, Japan and India.The main product is
the dried fruit body of G. applanatum used as traditional Family: Ganodermataceae
Chinese medicine and it has also been reported as a medicinal Genus: Ganoderma
farming crop and is used as a flavor enhancer in Asian cuisine Species: Ganoderma applanatum
because of its rich mushroom flavor. In Japan it is known
Binomial name: Ganoderma applanatum (Pers.) Pat.
as kofuki-saru-no-koshikake and and in China as shu-she-ling-
zhi (Asian Anticancer Material Database, 2021). No ancient Distribution and Morphology
time period had been mention for the traditional medicinal The mushroom has been reported from different countries of
uses of G. applanatum. Asia, Europe, North America and South America. Thus their
Lingzhi has been recognized as a medicinal mushroom for distribution can be considered cosmopolitan (CABI, 2020). In

Photo plate 1: Fig.1, 2 representing the front and back side of the basidiocarp ofG. applanatum (Dandapat et al.,2019b) and Fig.3 representing
basidiocarp of G. applanatum in groups; Fig. 4 diagrammatic representation of the cultured mycelia of G. applanatum; Fig. 5 showinghyphae
of the cutis (a), basidiospores (b), tube layer hyphae (c) and context hyphae (d) ofG. applanatum (Saha et al.,2018); Fig. 6 microscopic view of
spores of G. applanatum (Kuo M, 2018).

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MEDICINAL EFFICACY OF EDIBLE MACRO FUNGUS

India this taxon was previously reported from Maharashtra, microelements like Mn, Zn, Co, Mo, Ni and Cu are also required
Dehradun, Punjab, Assam and Jharkhand (Saha et al.,2018; and they are generally part of enzymes and cofactors.
Dandapat et al.,2019).The macrofungus is saprobic, perennial Microorganisms also require growth factors, which are organic
but releasing spore in summer and autumn. G. applanatum compounds (Basu et al.,2015)
grows alone or in groups on dead logs of hardwood, sapwood A culture media used for the in vitro culture of fungal mycelia
and conifers, also on living trees (Anand and Chowdhry, is composed of four basic components- essential elements
2013). and minerals, an organic supplement supplying vitamins and
The term Ganoderma is derived from the Greek word ganos: amino acids, a source of fixed carbon and a gelling agent
shining and derma: skin.The mushroom G. applanatum has (Ajdari et al.,2011; Kumar and Mina, 2019). In addition,
been identified on the basis of morphology and reported from various types of C and N sources could be utilized by fungi
time to time. The bases of morphological identification are due to their ability in secreting various enzymes for the
basediocarp, hyphal system and spores. The report on degradation of the polymers into small molecules (Lee et al.,
identification of G. applanatum by different workers is 2007). This means that the type and concentration of C and N
presented in Table-1 and Photoplate-1includes the list of sources, C/N ratio, and vitamins are the important factors in
identified structure of G. applanatum. medium formulation for the enhancement of fungal growth

Table 1: Description of G. applanatum basediocarp, hyphae and spores.


Sl. Basediocarp Hyphal system Spore References
No.
1 Dull grey, grey-brown to brown, No description Brown, elliptical, blunt Anand and
fan shaped, hard woody in texture. at the distal end, thick-walled, Chowdhry,
Size: 5.7-6.2cm broad × 5.5-11 ornamented with minute spines. 2013
cm thick. Pores: 4.2-5.8 per mm,
white.Multi-seried tubes: 3.7-14
mm long, separation of a thin
tissue layer.
2 Sessile, dull, non-laccate, woody, Trimitichyphal system. Basidiospore:double walled, Saha et al.,
applanate. 50–86 × 30–35 mm Yellowish-brown generative truncate 7.5–9× 3.5–4.5¼ 2018
in diameter and 35–44 mm thick. hyphae:thin walled, 4.5–5.5 mdiameters. , Exospores: hyaline,
Upper surface greyish to reddish- ¼m wide, clamp connection thin walled.Endospore: pale yellow
brown with concentric zonation, present at septa.Dark brown to dark brown, elongated ridges
whitish pore surface. branched skeletal hyphae: 4.5–6
¼m wide, and the hyaline binding
hyphae: branched, 1.7–2.5 ¼m wide.
3 Semicircular, 10–30 cm across, The older layers of tube often stuffed Ellipsoid, a truncated end, double- Kuo M.,
8–14 cm deep, dull, unvarnished with white mycelial material. walled, brown to orangish brown, 2018
outer crust surface, furrowed in zones 6–9 x 4–5 µm
,brownish to grayish brown. white
pore surface, dirty brown in age,
with 4–6 tiny circular pores per mm.
4 15 to 50cm across and 5 to 10cm thick, No description Brown, Ellipsoidal to ovoid, truncate Paulet al.,
off-white margin and a brown top.Lower at one end, smooth,6.5-8.5 x . 2008;
surface with small round pores, typically 4.5-6¼m First Nature,
five per mm, are white when the fruiting 2021.
body is young, turning brown with age or
when bruised.
5 3–30 cm wide × 5–50 cm long × 1–10 No description Brown spores were released from
cm thick, hard as leather, woody. The the pores on the underside of the Ginns J,
tubes are 4–12 mm deep and terminate fruiting body. 2017;
in pores that are round with 4–6 per Meuninck J.
millimetre. 2017
6 Semicircular, 13 cm in diameter,wrinkled No description No description Dandapat
zones of brownish to greyish-brown et al., 2019b.
colour at outer surface and the lower
surface is white.

Culture and Growth and sporulation. Although potato dextrose agar (PDA) and
Microbial culture media can be of different type, depending malt extract agar (MEA) are generally known as the most
on the nutritional growth requirements of the microorganisms. common media for growth and sporulation of fungi (Carvalho
Microorganisms require about 10 macro elements namely C, et al., 2005) they are only suitable for laboratory scale and
O, H, N, S, P, K, Ca, Mg and Fe. The first six components are might not be economic at large-scale production. However
used in the synthesis of Carbohydrates, Lipids, Proteins and microorganisms flourish at different environments and have
Nucleic acids and the remaining four exist in the cell as cations some environmental growth requirements like pH, osmotic
and play a variety of roles. In addition to macroelements, conditions, light and temperature.

3
SUKUMAR DANDAPAT et al.,

Woo-Sik Jo et al. (Woo-Sik et al.,2009) conducted an acids, lipids, steroid, terpenoids, alkaloids, phenolic
experiment to obtain basic information regarding the mycelial compounds, tannins, flavonoids, saponins, glycoside etc
culture conditions of Ganoderma applanatum. They focused (Singh et al.,2014; Nagaraj et al.,2013;Dandapatet al., 2019b).
mainly on the effects of pH, temperature, culture media, and Two new benzopyran-4-one derivativesapplanatin A
effects of nutrient sources such as carbon, nitrogen, carbon/ (C16H16O6), B (C16H18O6) and a ganoderma aldehyde commonly
nitrogen ratio, vitamins, organic acid and mineral salt on the known as ganoderenic acids were isolated and identified by
growth of G. applanatum mycelia. They reported 6-9 pH, 25- column chromatography and 13C NMR from chloroform-
30ºC temperature, PDA, YMA (yeast malt agar), MCM methanol extract of fruiting bodies of the fungus G.applanatum
(mushroom minimal media) and dark conditions showed (Wang et al., 2007).Palmitic acid is a major antibacterial
maximum growth of G. applanatum mycelia. They also found compound that was isolated, quantified by HPLC and TLC
among the used 10 carbon sources mannose, among the 13 from methanolic extract of G. applanatum and the molecular
nitrogen sources yeast extract, 5:1 C/N ratio, vitamins like structure of the compound was determined by Mass and 1H
thiamine-HCl and biotin, organic acid like succinic acid and
NMR spectroscopy (Moradali, 2008).By using GC-Mass and
lactic acid, salts like MgSO4, 7H2O, KH2PO4 and NaCl were
showed excellent growth of G. applanatum mycelia. H1NMR bioactive chemical compounds G1 (C20H34O4) with
chemical structure [(19,19a-dihydroxy-2-methyl-2,3,4,
In a similar work on mycelial growth of G. applanatum for 5,6,7,8,9,10,11,12,13,14,15 tetrad ecahydrobenzo[b]
exo-polymer production, (Yong et al.,2009) it was reported
oxacycloheptadecin-17(19aH] belongs to tannin group and
that the growth of G. applanatum mycelia was highest and a
pH of 4 to 6. Glucose served as a main carbon source among another compound G2 (C21H28O2) with molecular structure[(2-
the studied five different carbon sources (glucose, maltose, (2-(2,5- dihydroxyphenyl) ethylidene)- 11-hydroxy-6,10-
arabinose, mannose and molasses) and corn steep powder dimethylundeca-5,9-dienoic acid] belongs to terpenoides
served as main nitrogenous source among other studied group were isolated and identified from the mycelia culture of
nitrogen sources (yeast extract, peptone, meat extract, malt G. applanatum which showed potent bactericidal activity
extract) for the maximum production of mycelia (10.65 g/L to (Muhsin et al., 2011).
11.87 g/L). It was also reported maximum yield of mycelia A chemical analysis of ethanolic extract of mushroom G.
(18.0 g/L) was achieved at the end of log phase (12 days). applanatum was carried out through gas chromotaghrophy
Mycochemistry of G. applanatum coupled to mass spectrometry and first time reported six new
compounds:4-metil-ergosta-22-en-3 α -ol; 4,4-dimetil-ergosta-
Woody mushrooms normally grow as parasites or saprophytes
5,7,25(26)-trien-3 -ol; ergosta-5,7,9,24(28)-tetraen-3 α –ol;
on living trees or sometimes associated with logs of wood and
4,4-dimetil-ergosta-7,24(28)-dien-3 –ol; 17-isopropil-”5,7-3-
tree stumps. Species of Ganoderma are well known to cause
odroxiandrostadieno;and estigmasta-5,22-dien-3 a–ol
different types of rots by decomposing lignin as well as
(Guzman et al., 2013). In another study GCMS analysis of
cellulose and other related polysaccharides in both
methanolic extract of G. applanatum was performed and
angiosperm and gymnosperm hosts (Singh et al.,2014).Some
identified some principal components a-terpinene, D-
species of Ganoderma have been reported to contain different
limonene, cis-2-methyl-4-pentylthiane-s, s-dioxide, α -cymene
chemical constituents such as polysaccharides, proteins, and -terpinolene which possessed cytotoxic potential on
amino acids, fatty acids, terpenoids, steroids, alkaloids, different tumour cells (Hakkim et al., 2016).
phenolic compounds, etc. (Paterson, 2006; Boh et al., 2007)
with anti-inflammatory, anti-tumor, anti-oxidant, immun Quantitative estimation of secondary metabolites of
omodulatory, anti-diabetic, anti-viral, anti-bacterial, anti-fungal mushroom G. applanatum has been done from different
properties (Paterson, 2006; Kao et al., 2013; Singh et al.,2014). regions of world and the results showed variation in the
amount and composition of secondary metabolites.Nagaraj
Production of secondary metabolites is a common feature of
et al.(2014), estimated phenol (71 ±0.02 µg/mg) and flavonoid
fungi. It consists of a relatively small number of enzymological
(45±0.01µg/mg) in high quantity compared to tannin
processes which convert a few important intermediates of
(12.82±0.02µg/mg), saponin (5.91±0.01µg/mg) and steroid
primary metabolism into a wide range of products (Bu’Lock,
(13.45±0.01µg/mg) from methanolic extract of G.applanatum.
1961).Furthermore, fungal secondary metabolites are derived
In a similar study Rajoriya et al. (2015) quantified proximate
from a few common biosynthetic pathways which branch off
secondary metabolite from G. applanatum fruiting body. They
the primary metabolic pathways and are often produced as
found phenol (11.60±0.20 mg/g), caretonoid(7.43±0.29 mg/
families of related compounds, often specific for a group of
g) and alkaloid (4.40±0.25 mg/g) in high amount compared
organisms (Dewick P.M., 2009). The MVA and MEP pathway,
to the other trace metabolites such as -carotene, lycopene,
the shikimic acid pathway, the acetate pathway are the major
pathways for the synthesis of fungal secondary metabolites ergosterol, tannin, ascorbic acid and flavonoids.
such as terpenoids, aromatic amino acids and Mohammadifar et al. (2020) also performed a comparison
phenylpropanoids, polyketides respectively. Fungal alkaloids study between antioxidant activity and bioactive compounds
are commonly produced from amino acid through terpenes of G. applanatum and G. lucidum and reported the extract of
or acetate pathway (Hansoon D., 2013).Qualitative G. applanatum contain 6.70 mg/g phenolic compound and
biochemical screening of different solvent extracts of G. 1.37 mg/g flavonoid compound. They also quantified
applanatum fruiting body were carried out and found the terpenoid acids,ursolic acid and oleanolic acid in trace and
extracts of this mushroom carry wide range of primary as well 1.55mg/g betulinic acid by HPLC method.
secondary metabolites such as carbohydrates, proteins, amino Pharmacological and medicinal activities

4
MEDICINAL EFFICACY OF EDIBLE MACRO FUNGUS

Antimicrobial activity and Chou, 1984; Yang et al., 2002; Qureshi et al., 2010). It
G. applanatum possess a wide range of bioactive compounds has been experimentally reported the Ganoderma mycelia
and they showed broad spectrum antibacterial, antifungal and and fruiting body extracts inducing protein leakage within
antiviral activities. The mushrooms showed antibacterial bacterial cells due to their rich content of flavonoids and
activities against both gram-positive and gram-negative bacteria nucleobases (Mishra et al., 2018). During pathogenic invasion
(Gao et al.,2005). Artur et al.,(1999), studied the bactericidal extract of medicinal mushrooms induced generation of free
activity of isolated sterols 5 α -ergost-7en-3 α -ol, 5 α -ergost- radicals such as reactive oxygen species, peroxide radicals,
7,22-dien-3 -ol, and 5,8-epidioxy-5 α ,8 α -ergost-6,22-dien- and superoxide radicals etc. within bacterial cells, leading to
3 -ol against pathogenic ATCC and MIP strain bacteria cellular membrane damage as well damage intra cellular
Bacillus cereus, Corynebacterium diphtheria, E. coli, P. components such as DNA, intermediate enzymes involve in
aeruginosa , Staphylococcus aureus , Staphylococcus membrane synthesis etc (Zhang et al.,2015; Mishra et
saprophyticus , and Streptococcus pyogenes. They reported al.,2018).
gram-positives bacteria were more sensitive (MICs of 0.003 to Viral infections are amongst the most common diseases
2.0 mg/mL; MBCs of 0.06 to 4.0 mg/mL) than the gram-negative affecting people worldwide. New viruses emerge all the time
bacteria (MICs of 1.0 to 4.0 mg/mL; MBCs of 2.0 to > 4.0 mg/ and presently we have limited number of vaccines and only
mL). few antivirals to combat viral diseases. Fungi represents a vast
source of bioactive molecules, which could potentially be
The crude extracts of G. applanatum are also well known for
used as antivirals in the future (Rikka et al., 2018).Antiviral
their antimicrobial activities. A broad range of antibacterial
activity of G. applanatum has not been widely explored.
and antifungal activity of petroleum ether, chloroform,
Elkhateeb et al., (2020) studied the antiviral activity of
methanolic and aqueous extracts of G. applanatum fruiting
methanolic extract G. applanatum on simian rotavirus SA-11
body were screened against MTCC pathogenic bacteria S.
strains by MTT assay method and they found the extract
aureus, B. subtilis, E. coli, P. aeruginosa, K. pneumonia, S.
exhibited TI (CC50/IC50) =3.4 against virus infection.
typhi and four dermatophytic fungi C. albicans,C. indicum, T.
rubrum and M. gypseum by agar well diffusion method Antioxidant activity
(Nagaraj et al., 2013). Among the studied bacteria S. typhi Antioxidants are any substance, that delays, prevents, or
showed lowest inhibitory effect against all the extracts (only 8 removes oxidative damage to a target molecule (Halliwell B.,
±0.24 mm zone of inhibition against methanolic ectract) and 2007).Antioxidant compounds are broadly classified into
S. aureus showed highest sensitivity (15±0.21 mm to 8± natural or primary and synthetic or secondary antioxidants.
0.21 mm zone of inhibition) against all the studied extracts. They are the chain breaking molecules which react with free
α Among the studied fungal strains C.albicans (10± 0.23mm to radicals and convert them into more stable products. They
5± 0.2mm ZOI) and C.indicum (7± 0.18 mm to 5± 0.1 mm are mainly derived from the natural sources such as
ZOI) showed high inhibition to all the extracts. antioxidant minerals, vitamins, secondary metabolites of plants
Monika et al. (2014), studied the antibacterial activity of isolated and higher fungi etc. Secondary antioxidants are compounds
exopolysaccharide from stationary cultures of G. applanatum that perform the function of capturing free radicals and
against E. coli and S. aureus strains. The exopolysaccharide stopping the chain reactions and include compound such as
showed 17.9mm inhibition zone of and 1mg/mL MIC against butylated hydroxyanisole (BHA), butylated hydroxytoluene
S. aureus but no inhibition was observed against E. coli. (BHT), tertiary butyl hydroquinone (TBHQ), nordi
hydroguaiaretic acid (NDGA) etc (Carocho et al.,2013;
Bactericidal activities of purified polysaccharides and hot alkali
Rasheed et al., 2019).
extract of wild G.applanatum were examined against some
other bacterial species such as Listeria monocytogenes, Oxidative stress is a phenomenon caused by an imbalance
Geobacillus stearothermophilus, Enterococcus faecalis, between production and accumulation of free radical species
Proteus hauseri, Salmonella enteritidis, Shigella sonnei and (reactive oxygen species, reactive nitrogen species, reactive
Yersinia enterocolitica(Klaus et al.,2016) and found the alkali sulfur species, reactive carbonyl species etc.) in cells and
extract (MIC: 0.039 mg/mL to 1.25 mg/mL; MBC: 1.25 mg/mL tissues and their intensity wise ranging from physiological
to 10.0 mg/mL) was most effective than the partially purified oxidative eustress to excessive and toxic oxidative distress
polysaccharide (MIC: 0.156 mg/mL to 5.0 mg/mL; MBC: 2.5 (Yan L.J., 2017). Free radicals are generated from both
mg/mL to 10.0mg/mL). Bacterial growth inhibitory activity of endogenous and exogenous sources. Immune cell activation,
methanol, ethanol, chloroform and aqueous extracts inflammation, ischemia, infection, cancer, excessive exercise,
G.applanatum has been studied by agar well diffusion and mental stress, and aging are all responsible for endogenous
broth dilution method against urethitis, cystitis, prostatitis and free radical production. Exogenous free radical production
pneumonia causing bacteria Proteus mirabilis (Dandapat et can occur as a result from exposure to environmental
al., 2016) and has been found that all the extracts, in both the pollutants, heavy metals, certain drugs, chemical solvents,
methods adopted, showed 100% inhibition indicating 1.98± cigarette smoke, alcohol, and radiations etc. (Valkoet al.,
0.01 to 3.02 ±0.03 mm ZOI with 800 µg/mL MIC. 2006; Valko et al., 2007).
It is reported that antimicrobial compounds such as terpenes, At low or moderate concentrations, free radicals play several
lectins, polysaccharides etc. act on the bacterial cytoplasmic beneficial roles such as elimination of intracellular pathogens,
membrane to make them more permeable for autolysis (Lin tumor cells, and play regulatory role in intracellular signaling
cascades (Pizzino et al.,2017). Oxidative distress is associated

5
SUKUMAR DANDAPAT et al.,

with several patho-physiological conditions and one on the related to the brain and lymph nodes (Rahman et al., 2014).
leading cause of cardiovascular diseases, chronic obstructive Chemical drugs for cancer treatment, such as cisplatin and
pulmonary disease, chronic kidney disease, neuro cyclophosphamide, can cause side effects, such as
degenerative diseases, and cancer including sarcopenia and nephrotoxicity, which are detrimental to the quality of life of
frailty etc. (Liguori et al.,2018).Chemical composition and patients (Aguirre et al., 2013). In addition to this toxicity, the
antioxidant potential of mushrooms have been intensively resistance of some cancer cells to treatment has led to the
studied and found edible mushrooms might be used directly need for the evaluation of alternative approaches (Yu et al.,
in enhancement of antioxidant defenses through dietary 2018).
supplementation to reduce the level of oxidative stress. Wild It has been reported the anti-cancer compounds of mushroom
or cultivatedmushrroms have been related to significant play crucial role as reactive oxygen species inducer, mitotic
antioxidant properties due to their bioactive compounds, such kinase inhibitor, anti-mitotic, angiogenesis inhibitor,
as polyphenols, polysaccharides, vitamins, carotenoids and topoisomerase inhibitor, leading to apoptosis, and eventually
minerals (Kozarski et al.,2015). checking cancer proliferation (Patel et al., 2012).The main
Ganoderma species are G. lucidum, G. sinensis, G.
In vitro antioxidant activity of G. applanatum petroleum ether, applanatum, G. tsugae, G. atrum, G. formosanum, G.
chloroform, methanol and aqueous extract were determined microsporum, and G. atrum. They have been studied and
by DPPH scavenging assay, reducing power assay, metal broadly explored for anticancerous and other medicinal
chelating assay, hydroxyl radical scavenging assay, superoxide properties (Yu et al., 2018).
radical scavenging assay. The methanolic extract showed
Antitumor effect of exo-polymer produced by G. applanatum
higher DPPH radical scavenging activity (IC50:135.13 µg/mL),
was investigated using sarcoma-180 bearing mice and
ferric reducing activity (0.85%), Fe2+ chelating activity (IC50: significant growth inhibition of solid tumor and increase natural
50.84 µg/mL), compared to the other extract, hydroxyl radical killer (NK) cell activity as well phosphatase activity was found
scavenging activity (IC50: 104.89 µg/mL to 112.78 µg/mL), (Yong-Tae et al., 2008). Antitumor activity of extracellular
superoxide radical scavenging activity (IC50: 111.94 µg/mL polysaccharide from cultured mycelia of G. applanatum was
and 120 µg/mL) compared to the other extract (Nagaraj et al., investigated in vitro by MTT assay against cervical carcinoma
2014).Rajoriya et al.(2015),studied and reported G. cell lines SiHa and CaSki (Monika et al.,2014). A significant
applanatum methanolic extract showed 91.64% DPPH radical cytotoxic activity with 42.8% and 34% decrease in cell viability
scavenging activity with IC50=6mg/mL.Antioxidant activity of of SiHa carcinoma at 22.88 5µg/mL and 228.5 5µg/mL
exoploysaccharide of G. applanatum mycelia was studied concentrations of the exopolysaccharides was observed
and reported, the exopolysaccharides of G. applanatum strain respectively. It has been reported that polysaccharides from
effectively scavenged hydroxyl radicals (63.9±0.1%) and Ganoderma species inhibited tumor growth via induction of
superoxide anion radicals (58.8±0.1) (Liu et al., 2015). apoptosis through mitochondrial pathways and immuno
Anticancer activity enhancement effects (Li et al., 2011).A dose dependent anti-
Cancer is a major public health problem, being one of proliferative activity of terpenoid compounds from methanolic
thehighest causes of death in both men and women in extract of G. applanatum was studied against triple negative
developed as well as developing countries (Baliga et al., 2012; breast cancer cells (MDA-MB-231) and cervical cancer cells
Rahman et al., 2014). Approximately 12.7 million new cancer (HEp-2) and found after 24 hours of treatment the carcinoma
cases and 7.6 millioncancer deaths occurred near 2008. By cells lost their adherence and morphology and were found to
the year 2020, predictions report that the incidence of cancer be necrotic (Faruck et al., 2016). Recently both in vivo and in
may increase 3-fold, with a disproportionate rise in cancer vitro anticancer study of G. applanatum secondary metabolites
cases and deaths in developing countries (Rahman et al., was carried out and reported that the G. applanatum inhibit
2014).Cancer occurs by successive mutations in genes that the proliferation and viability of colon cancer cell (Ccco-2)
changes cell functions. Chemical compounds have an obvious and decrease the volume of solid developed Ehrlich tumor by
role of forming gene mutations and cancer cells but other activating apoptosis through p53-independent and p53-
factors such as smoking,viruses, bacteria, and radiation rays dependent path ways (Elkhateeb et al., 2018).
are other carcinogenic factors, comprising about 7% of all Anti-inflammatory activity
cancers (Parkin D.M., 2006; Rahman et al., 2014). In general, Inflammation is considered to be part of the complex biological
cancer disrupts cellular relations and results in the dysfunction response to remove injury or harmful stimuli such as
of vital genes and this disturbance is affective in the cell cycle, pathogens, damaged cells, or irritation. Inflammation leads to
and leads to abnormal cell proliferation (Seto et al., 2010; many physiological symptoms such as fever, pain, and
Rahman et al., 2014). swelling, vasodilation, increased vascular permeability etc. In
Cancer in the broader sense refers to more than 277 different recent era nonsteroidal anti-inflammatory drugs (NSAIDs) are
types of cancer disease. In men commonly the highest commonly used to treat inflammation but long-term use of
percentage of cancer occurs in the prostate, lung and bronchus, NSAIDs induce side effects such as mucosal lesions, bleeding,
colon and rectum, and urinary bladder, and in women most peptic ulcers, intestinal perforation etc. (Sinha et al., 2013).
prevalence cancer occur in the breast, lung and bronchus, Side effects of NSAIDs are not limited only to GI-tract but extend
colon and rectum, uterine corpus and thyroid (Siegel et al., to serious situations such as acute renal failure, nephrotic
2016;Rahman et al., 2014) . For children, the highest syndrome, hypertension, and cardiovascular toxicity etc.
percentage types of cancer are blood cancer, and cancers (Meek et al., 2010).

6
MEDICINAL EFFICACY OF EDIBLE MACRO FUNGUS

Anti-inflammatory effects with anti-inflammatory compounds experimental rats as presented in Table 2.


of mushrooms involve a highly diversified group of Ganoderma applanatum exo-polymer (GAE) produced by
biochemicals. They include polysaccharides, terpenoids, submerged mycelial cultures substantially reduced the plasma
phenolic compounds, and many other low molecular weight glucose levels by as much as 22.0% in streptozotocin induced
molecules (Elsayed et al., 2014).Ganoderma extract treatment diabetic rats, when compared with the control group (Yang et
leds to significant increases in the percentages of CD4+, CD25+, al., 2007). Oral glucose tolerance test is a standard procedure
Foxp3+, Treg and IL-10+ Breg cells, together with a reduction to identify persons at high risk for type-II diabetes (Stern et al.,
in the plasma concentrations of several inflammatory cytokines 2002). It is a widely utilized method which has been used to
and down-regulated expression of the corresponding cytokine evaluate the α -cell function and insulin resistance (Stumvoll
related genes in systemic lupus erythematosus include et al., 2000). G. applanatum methanolic and chloroform
inflammation of the joints, joint pain, and edema (Cai et al., extracts(500mg/kg b.wt.) also significantly maintained the
2016).In an in vitro experiment ethanol extract of G. glucose homeostasis in alloxan induced diabetic rats by
applanatum showed dose dependent anti-inflammatory inhibiting the rise in plasma glucose levelscompared to post
activity. The ethanol extract of G. applanatum at a dose of 600 versus pre-prandial plasma glucose levels which is nearly
mg/kg showed maximum suppression of oedema (59.2%) in similar to normal control and positive control rats. The
the rat paw. Along with anti-inflammatory activity the extract presence of various secondary metabolites helps to restore
also prolonged the reaction time in mice to noxious thermal the capacity of pancreatic α -cells, stimulating insulin secretion
stimuli (Ede et al., 2012). and glucose uptake by the peripheral tissues (Ruby et al.,
Antidiabetic activity 2018; Hossain et al., 2021).
Diabetes mellitus is a group of physiological dysfunctions Hepatoprotective and Nephroprotective activity
characterized by hyperglycemia resulting directly from insulin The liver is one of the most important organs of the body and
resistance, inadequate insulin secretion, or excessive glucagon performs elementary role in the regulation of different
secretion. Type-1 diabetes (T1D) is an autoimmune disorder physiological processes, and its activity is related to different
leading to the destruction of pancreatic beta-cells and type-2 vital functions, such as metabolism, secretion, and
diabetes (T2D) is most common and is primarily a problem of storage.Hepatic diseases continue to be among the principal
progressively impaired glucose regulation due to a threats to public health, and they are a problem worldwide
combination of dysfunctional pancreatic beta cells and insulin (Adewusi and Afolayan, 2010; Madrigal-Santillan et al., 2014).
resistance (Blair M., 2016). Due to imbalance of specific Hepatic disease is a term that indicates damage to the cells,
receptors such as Glucagon-like peptide-1(GLP-1) receptor, tissues, structure, or liver function, which can be induced by
peroxisomes proliferator activated (a) receptor (PPARa), beta3 biological factors (bacteria, virus, and parasites) and
( α 3) ardent-receptor some enzymes like α glycosidase, autoimmune diseases (immune hepatitis, primary biliary
dipeptidyl peptidase IV enzyme etc. can cause diabetes cirrhosis), as well as by the action of different chemicals, such
mellitus (Nishita et al., 2016). as some drugs (high doses of paracetamol and antitubercular
In vivo antidiabetic activity of G. applanatum extract and drugs), toxic compounds (CCl4, thioacetamide, dim
secondary metabolites has been studied on streptozotocin ethylnitrosamine, D-galactosamine/lipopolysaccharide), and
and alloxan induced diabetic animal. Streptozotocin is a unquestionably, excessive consumption of alcohol (Deshwal
glucosamine nitrosourea compound that induces diabetes et al., 2011; Madrigal-Santillan et al., 2014). Injury to the
either by inactivation of the GLUT2 glucose transporter liver, whether acute or chronic, eventually results in an increase
in serum concentrations of total bilirubin (TB), aspartate
receptor of α -cells or by the destruction of α - cells (Graham
aminotransferase (AST), alanine aminotransferase (ALT) and
et al., 2011). Alloxan is a pyrimidine, structurally similar to
alkaline phosphatase (ALP) (Gowda et al., 2009). In normal
glucose and uric acid directly disrupt α -cell membrane
rats G. applanatum aqueous extract showed no significant
permeability and inhibition of tricarboxylic acid cycle and effect on TB, AST, ALT and ALP but significant elevation in
Ca2+- dependent dehydrogenases in the mitochondria causes serum albumin and protein level was observed (Dandapat et
ATP deficiency, cessation of insulin production, and eventual al., 2019). In an experiment significantly decrease AST, ALT,
α -cell death (Schmeltz et al., 2006). Hossain et al., (2021) ALP, total bilirubin and increase in albumin level in alloxan
reported very effective impact on blood glucose levels in induced diabetic rats group was observed compared to the
Table 2: Effect of Methanol extract (MEGA) and Aqueous extract (AEGA )on blood glucose level in different groups of experimental rats
(Hossain et al., 2021)
Groups Blood glucose level (mg/dl)
Day 1 Day 4 Day 7 Day 9
I: Normal control 96.50 ± 3.73 99.83 ± 4.96 97.00 ± 3.16 100.17 ± 3.49
II: Diabetic control 285.83 ± 11.48 a 290.50 ± 9.59 a 303.50 ± 6.06 a 305.83 ± 6.05 a
III: Diabetic + MEGA (250 mg/kg) 135.83 ± 6.79 a 127.83 ± 5.49 a
119.17 ± 4.26 a 108.33 ± 4.32 a
IV: Diabetic + MEGAb (500 mg/kg) 129.17 ± 2.99 a 117.50 ± 10.03a 108.00 ± 3.03 a 102.00 ± 3.69 a
V: Diabetic + AEGA (250 mg/kg) 149.33 ± 4.18 a 133.00 ± 5.69 a 127.67 ± 5.96 a 124.33 ± 4.89 a
VI: Diabetic + AEGA (500 mg/kg) 142.17 ± 4.17 a 127.67 ± 4.76 a 124.33 ± 4.41 a 110.33 ± 5.82 a
VII: Diabetic + glibenclamide (1 mg/kg) 123.50 ± 3.73 a 98.83 ± 7.63a 91.33 ± 4.27a 86.50 ± 6.22a
Groups III, IV, V, VI, and VII compared with diabetic control.a =p < .001, b= p < .01, c =p < .05.

7
SUKUMAR DANDAPAT et al.,

diabetic control group (TB- 1.38 ± 0.18 mg/dL,ALB- 2.87 ± reduce the serum LDL significantly. Low triglyceride levels
0.19 mg/dL, AST- 52.33 ± 4.72 mg/dL, ALT- 126.33 ± 5.79 can contribute to decreasing the availability of fatty acids for
mg/dL, ALP- 248.83 ± 5.46 mg/dL) when treated with 500mg/ esterification (Packard et al., 2020), increased catabolism of
kg G. applanatum methanolic extract (TB-1.35 ± 0.11 mg/dL, LDL, activation of tissue lipases, and decreased production of
ALB-3.20 ± 0.28 mg/dL, AST-25.00 ± 3.74 mg/dL, ALT-98.00 precursors of triglycerides (McCarty, 2001; Packard et al.,
± 4.38 mg/dL, ALP-224.17 ± 3.87 mg/dL) and aqueous extract 2020; Hossain et al., 2021).This observed restoration of the
(TB-1.33 ± 0.13 mg/dL,ALB-3.20 ± 0.30 mg/dL, AST-30.00 alloxan-evoked changes in the serum lipid profile shows the
± 5.10 mg/dL, ALT-98.83 ± 3.25 mg/dL, ALP-228.00 ± 5.22 protective nature and hypolipidemic effect of G.
mg/dL) (Hossain et al., 2021).It has also been reported applanatum.The suggestion is that reductions in intestinal
sulfated Ganoderma applanatum residue polysaccharides act cholesterol and bile acid absorption after the feeding of G.
as potent antifibrotic agent and reduce histopathological applanatum methanolic extract and G. applanatum aqueous
damages, down-regulated cytochrome P450 2E1 expression, extract may represent main mechanism for hypolipidemic
reduced serum AST and ALT, improved the anti-oxidative and mechanisms of G. applanatum(Nagaoka et al., 2005; Hossain
anti-inflammatory properties, inhibited TLR4/NF-kB signaling et al., 2021).
pathway, and reduced the release of inflammatory cytokines Hypouricemic activity
(Xinling et al.,2021). In recent years, a large body of evidence has accumulated that
Chronic kidney disease recognized as a major risk factor for suggests that hyperuricemia may play a role in the
the development of new acute kidney injury, and acute kidney development and pathogenesis of a number of metabolic,
injury now accepted to lead to de novo or accelerated chronic hemodynamic, and systemic pathologic diseases, including
and end stage kidney diseases (Ferenbachand Bonventre, metabolic syndrome, hypertension, stroke, and atherosclerosis
2016).Chronic kidney disease is most commonly attributed (Billiet et al., 2014). Hyperuricemia has long been established
to diabetes and hypertension (Coca et al., 2012). Acute kidney as the major etiologic factor in gout. It is the most well
injury (AKI) describes a sudden loss of kidney function that is understood and described type of arthritis. Gout is
determined on the basis of increased serum urea, creatinine, characterized with reoccurring inflammatory arthritis, which
uric acid levels and oliguria (Gowda et al., 2010;Kellum et al., is triggered by the crystallization of serum uric acid (SUA) in
2021).Dandapat et al., (2019), reported the aqueous extract the joints and is often caused by hyperuricemia (Choi et al.,
of G. applanatum showed a nephro protective activity in 2005) G. applanatum ethanolic and aqueous remarkably
nomal rat and significantly decrease serum urea lowered the level of serum uric acid via elevated urin uric acid
(57.62±0.74mg/dL),creatinine (0.86±0.008mg/dL) and uric levels in potassium oxonate and hypoxanthine induced
acid (14.24±0.73mg/dL) level compared to control treatment hyperuricemia mice, there by confirming the uricosuria effect
groups of rat (SU: 62.32±1.17 mg/dL; CRE: 0.93±0.01 mg/ (Yong et al., 2018). Ethanolic and aqueous extract did not
dL; UA: 22.5±0.70mg/dL). decrease the XOD activity; hence the hypouricemia effects of
Antihyperlipidemic activity G. applanatum may be raised by other methods, such as
Hyperlipidemia is a medical condition characterized by an uricosuria or anti npurine absorption pathways. It has been
increase in one or more of the plasma lipids, including reported renal transporters, including OAT-1, GLUT-9, and
triglycerides, cholesterol, cholesterol esters, phospholipids and URAT-1, are directly associated with the homeostasis of serum
or plasma lipoproteins including very low-density lipoprotein uric acid (Anzai et al., 2010; Yong et al.,2018). Both ethanolic
and low-density lipoprotein along with reduced high-density and aqueous extract of G. applanatum increased the mRNA
lipoprotein levels (Shattat G.F., 2014). Elevated levels of and protein levels of OAT-1, inducing the remarkably
cholesterol (hypercholesterolemia) and abnormal lipid profiles enhanced uric acid excretion by advancing the uric acid
(dyslipidemia) are important risk factors for cardiovascular transportation through OAT-1. The extracts also enhanced
disease (CVD) and the most common forms of the CVD are the excretion of uric acid by inhibiting the uric acid
hypertension, coronary heart disease (CHD), stroke, and heart reabsorption through GLUT-9. Further more, ethanol extract
failure etc (Mensah and Brown, 2007; Schaiff et al., 2008).In down regulated the level of URAT-1 protein (Yong et al., 2018).
vitro hypocholesterolemic activity of G. applanatum extract Notably, the upregulation of OAT-1 and down regulation of
was studied and reported that the cholesterol reduction activity GLUT-9 and URAT-1 correlated to urine uric acid provided
increases proportionally with the increase in concentration of the evidence that the synergistic activity of OAT-1, GLUT-9,
the extract, and elongation of incubation time (90.9±1.0% to and URAT-1 by G. applanatum contributed to the uricosuria
100.0±0 % reduction after 96 hours) (Elkhateeb et al., actions.
2020).Hossain et al., (2021),reported methanolic extract of
Anti- Alzheimer’s activities
G. applanatum significantly decrease total cholesterol, LDL
cholesterol and triglyceride in extract treated diabetic rats (TC: Alzheimer’s disease (AD) has progressive neuro degenerative
48.83 ± 2.79 mg/dL, LDL-C: 11.83 ± 2.32 mg/dL, Triglyceride: pathology with severe economic and social impact. AD is the
81.50 ± 2.74)compared to control rats (TC: 66.83 ± 2.71mg/ dementia associated with aging, which initially targets memory
dL, LDL-C: 26.67 ± 3.01mg/dL, Triglyceride: 107.50 ± and progressively destroys the functions of the brain, as the
4.14mg/dL). However a significant increase in HDL cholesterol neocortex suffers neuronal, synaptic, and dendritic losses.
(31.50 ± 1.87 mg/dL) of extract treated diabetic rats was There is currently no cure, although cholinesterase
observed compared to control group (28.00 ± 1.41 mg/dL). inhibitors provide effective temporary relief of symptoms in
The suppression of LDL oxidation by G. applanatum may some patients (Saify et al., 2014). Treatment of AD has been

8
MEDICINAL EFFICACY OF EDIBLE MACRO FUNGUS

dominated by the use of acetylcholinesterase (AChE) 1-9.


inhibitors. These drugs compensate for the death of cholinergic Anand, N. and Chowdhry, P.N. 2013. First report on five hitherto
neurons and offer symptomatic relief by inhibiting unreported macro fungi from Rajouri district of Jammu & Kashmir
acetylcholine (ACh) turnover and restoring synaptic levels of (J&K), India. Annals of Biological Research. 4(5): 62-70.
this neuro transmitter (Rees and Brimijoin, 2003). Nowadays, Anzai, N., Jutabha, P. and Endou, H. 2010. Renal solute transporters
drug research and development are based on the cholinergic and their relevance to serum urate disorder. Curr. Hypertens. Rev. 6:
hypothesis that supports the cognition improvement by 148-154.
regulation of the synthesis and release of acetylcholine in the Asian Anticancer Material Database. 2021. Ganoderma applanatum.
brain (Saify et al., 2014).Both methanolic and aqueous extract http://www.asiancancerherb.info/Shu%20She.htm
of G. applanatum showed cholineesterase inhibition activity Baliga, M.S., Thilakchand, K.R., Rai, M.P., Rao, S. and Venkatesh, P.
but the methanolic extract had high acetyl cholinesterase (1.45 2012. Aegle marmelos (L.) Correa (Bael) and its phytochemicals in
± 0.01 mg gallic acid equivalents per g extract) and butyryl the treatment and prevention of cancer. Integr. Cancer Ther. 12(3):
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2015). S. 2015. Evolution of bacterial and fungal growth media.
Immunemodulatory activity Bioinformation. 11(4): 182 – 184.
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Rheumatol. 852954.
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cytokines or cytokines inhibitor such as IL-4, IL-10, and IL-13 Biotechnol. Annu. Rev. 13: 266-231.
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Cai, Z., Wong, C.K., dong, J., Jiao, D., Chu, M., Leung, P.C., Lau,
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C.B.S., Lau, C.P., Tam, L.S. and Lam, C.W.K. 2016. Anti-inflammatory
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Immunomodulatory activity of G. applanatum Carocho, M. and Ferreira, C.F.R. 2013. A review on antioxidants,
exopolysaccharide was investigated using THP-1, an acute prooxidants and related controversy: Natural and synthetic
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by 752.17 pg/mL, representing an approximately 54-fold
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level to 190.52 pg/mL was observed after 24-hour Choudhary, M., Devi, R., Datta, A., Kumar, A. and Jat. H.S. 2015.
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