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A new highly oxygenated triterpene named ganoderic acid α has been isolated from a methanol extract of the fruiting bodies of Ganoderma lucidum together with twelve known compounds. The structures of the isolated compounds were determined by spectroscopic means including 2D-NMR. Ganoderiol F and ganodermanontriol were found to be active as anti-HIV-1 agents with an inhibitory concentration of 7.8 μg ml−1 for both, and ganoderic acid B, ganoderiol B, ganoderic acid C1, 3β-5α-dihydroxy-6β-methoxyergosta-7,22-diene, ganoderic acid α, ganoderic acid H and ganoderiol A were moderately active inhibitors against HIV-1 PR with a 50% inhibitory concentration of 0.17–0.23 mM.
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Research Institute for Traditional Sino-Japanese Medicines, Toyama Medical and Pharmaceutical
University, 2630 Sugitani, Toyama, 930-0194, Japan, $Institute for Virus Research, Kyoto University,
53 Kawara-machi, Showgoin, Sakyo-ku, Kyoto, 606-8397, Japan and %Osaka Prefectural Institute of
Public Health, 3-69 Nakamichi 1-chome, Higashinari-ku, Osaka, 537-0025, Japan
(Received 20 October 1997)
Key Word IndexÐGanoderma lucidum; Polyporaceae; bioactive plant products; anti-HIV-1;
HIV-1-protease; triterpene; ganoderiol F; ganodermanontriol.
AbstractÐA new highly oxygenated triterpene named ganoderic acid ahas been isolated from a methanol
extract of the fruiting bodies of Ganoderma lucidum together with twelve known compounds. The structures
of the isolated compounds were determined by spectroscopic means including 2D-NMR. Ganoderiol F and
ganodermanontriol were found to be active as anti-HIV-1 agents with an inhibitory concentration of
7.8 mgml
for both, and ganoderic acid B, ganoderiol B, ganoderic acid C1, 3b-5a-dihydroxy-6b-methoxy-
ergosta-7,22-diene, ganoderic acid a, ganoderic acid H and ganoderiol A were moderately active inhibitors
against HIV-1 PR with a 50% inhibitory concentration of 0.17±0.23 mM. #1998 Elsevier Science Ltd. All
rights reserved
Over the past decade, substantial progress has been
made in de®ning strategies for the treatment of
human immunode®ciency virus (HIV)-infected dis-
ease, acquired immunode®ciency syndrome (AIDS),
where natural products can serve as a source of
structurally novel chemicals that are worth investi-
gating as speci®c inhibitors of HIV as well as its
essential enzymes, protease (PR) and reverse tran-
scriptase (RT).
The fruiting body of Ganoderma lucidum
(Japanese name: Reishi) is one of the valuable
crude drugs, which has long been used in China
and Japan as a traditional Chinese medicine or a
folk medicine for the treatment of various kinds of
diseases [1]. Several biologically active triterpenes
and sterols have been isolated from this mushroom
and proved eective as cytotoxic [2, 3], antiviral [4]
and antiin¯ammatory agents [5, 6]. Polysaccharides
and glycoproteins possessing hypoglycemic [7, 8]
and immunostimulant [9±13] activities have also
been isolated from a water extract. In the course of
our continuing search for natural products as anti-
HIV agents, a methanol extract of the fruiting
bodies was found to be moderately active for inhi-
bition of HIV-1-induced cytopathogenicity (com-
plete inhibition at 31.3 mgml
in MT-4 cells) and
of its essential enzyme, protease (PR) (ca. 50% inhi-
bition at 100 mgml
). Therefore, this extract was
selected for further fractionation. When subjected
to bioassay-guided fractionation, the extract yielded
several active compounds. This paper describes the
isolation of thirteen compounds, and their inhibi-
tory eects against HIV-1 and its enzyme PR.
Isolation and structure determination of compounds
isolated from the fruiting bodies of Ganoderma luci-
Bioactivity-guided fractionation of the methanol
extract enriched the anti-HIV-1 and HIV-1-PR in-
hibitory eects in two fractions B and C. Final
puri®cation of the active compounds was achieved
by repeated column chromatography and HPLC to
give thirteen compounds, 4,5,8and 9from frac-
Phytochemistry Vol. 49, No. 6, pp. 1651±1657, 1998
#1998 Elsevier Science Ltd. All rights reserved
Printed in Great Britain
0031-9422/98/$ - see front matter
PII: S0031-9422(98)00254-4
*Author to whom correspondence should be addressed.
Fax +81-764-34-5060, E-mail: saibo421@ms.toyama-
tion B, and 1±3,6,7and 12 from fraction C. Three
compounds 10,11 and 13 were also obtained from
fraction A. The structures of the known compounds
were identi®ed on the basis of their spectroscopic
properties when compared with those reported for
ganoderic acids A (2) [14±16], B (3) [14±16], C1
(4) [16, 17] and H (5) [18, 19], ganoderiols A (6) [20],
B(7) [20] and F (8) [21], and ganodermanontriol
(9) [20], (all were previously isolated from the same
mushroom). In addition, ergosterol (10), ergosterol
peroxide (11, previously isolated from the sponge
Ascidia nigra) [22], cerevisterol (12) [23, 24] and
3b-5a-dihydroxy-6b-methoxyergosta-7,22-diene (13)
(both were previously isolated from the mushroom
Agaricus blazei) [24] were identi®ed (Fig. 1).
Compound 1was obtained as an amorphous
powder, [a]
). A molecular formula
of C
was estimated from a molecular ion at
m/z 574 [M]
in its EI-MS. The UV absorption at
254 nm and the IR band at 1650 cm
suggested the
presence of a conjugated ketone group. The
H NMR spectrum of 1analyzed by the aid of
Fig. 1. Structures of compounds isolated from a methanol extract of the fruiting bodies of Ganoderma
S. EL-MEKKAWY et al.1652
H COSY and HMQC experiments showed signals
for seven methyls (including two as doublet at d
0.97 and 1.17), and three methine protons at d3.27
(dd,J= 11.0 and 4.8 Hz), 4.80 (t,J= 8.5 Hz) and
5.62 (s) (Table 1). In addition, a singlet at d2.23
for an ester methyl was also seen. The
and DEPT spectra demonstrated signals character-
istic for eight methyls, seven methines (including
three oxymethines at d66.2, 77.3 and 79.1), and ele-
ven quaternary carbons (including ®ve carbonyls at
d170.2, 181.0, 193.9, 199.0 and 206.1) (Table 1).
These data suggested a highly oxygenated lanos-
tane-type triterpene close to the structures of 3,5
and ganoderic acids G (14) [18] and K (15) [25].
However, the dierence in chemical shift between
C-8 and C-9 (6.1 ppm) in 1suggested that its substi-
tution pattern in rings B and C was similar to that
of 5, when compared to that reported for 5(about
6.0 ppm) and 3/14 (about 16.5 ppm). The EI-MS
(Fig. 2a) showed prominent fragment ions at m/z
514 [M-HOAc]
corresponding to the loss of an
acetoxyl group (as acetic acid) from the molecule,
and successive losses of 18 mass units (m/z 496 and
478) indicating the presence of two hydroxyl
groups. The fragment ions m/z 417 [a]
and 115
(resulted from the cleavage between C-22 and
C-23) suggested the same side chain as in related
ganoderic acids. Acetylation of 1with Ac
dine yielded a triacetate (1a) (EI-MS m/z 658 [M]
two additional ester methyl proton signals at d2.05
and 2.10), thereby providing evidence for the pre-
sence of two hydroxyl groups in 1.
The precise connectivities of 1were established
by interpretation of the HMBC data summarized in
Table 1. Long-range correlations between H-5 and
C-7/C-9; H-30 and C-8; H-19 and C-9; and H-12
and C-11 con®rmed the diketone substitution at C-
7 and C-11. Correlations between H-18 and C-12,
and between H-12 and a carbonyl carbon signal at
d170.2 (IR, 1730 cm
) revealed the connectivity of
the acetoxyl group at C-12. Since H-28 and H-29
were shift-correlated with C-3, a hydroxyl group
was concluded to be located at C-3. On the other
hand, the
H correlations between H-15 and H-
16a and H-16b led to the presence of the other hy-
droxyl group at C-15.
The relative stereochemistry of 1was con®rmed
by measuring the NOESY and NOE dierence
spectra of 1a as shown in Fig. 2b. The NOE
observed between H-3 (d4.48, dd,J= 11.3,
4.9 Hz), H-29 (d0.91) and H-5 (d1.65), con®rmed
the b-con®guration of the acetoxyl group at C-3,
which was equatorially oriented. Similarly, the b-
con®guration of the acetoxyl group at C-12 was
inferred from the correlations observed between H-
12 (d5.67) and the proton signal at d1.42 (H-30).
Appreciable enhancement of H-15 (d5.89) upon ir-
radiation of H-30, and vice versa, together with no
evidence of spatial correlations between H-15 and
H-18 (d0.89), con®rmed the b-con®guration of an
acetoxyl group at C-15 (d68.9). The NOE between
H-17 (d2.54) and both of H-12 and H-30 (in the
NOESY spectrum of 1) con®rmed the con®guration
at C-17. As regards the stereochemistry at C-25, the
absolute con®guration was suggested to be R, when
compared with that of ganoderic acid H (3, given
the name ganoderic acid C by Hirotani et al. [26])
having the same side chain which was con®rmed by
X-ray analysis. On the basis of the above ®ndings,
compound 1was determined as 12b-acetoxy-
oic acid and named ganoderic acid a.
Inhibitory eects of isolated compounds on HIV-1-
induced cytopathogenicity, HIV-1-protease and HIV-
1-reverse transcriptase
Investigation of anti-HIV-1 and PR-inhibitory ac-
tivities of compounds 1-13 showed that some com-
pounds had moderate inhibitory activity (Table 2).
In the primary screening test for anti-HIV-1 ac-
tivity, compounds 8and 9were found to inhibit
HIV-1 induced cytopathic eect (CPE) in MT-4
cells with a 100% inhibitory concentration (IC)
value of 7.8 mgml
for both compounds, and the
IC value for both was a half of the respective cyto-
toxic concentration (CC) value.
As for HIV-1 PR inhibitory eects, the activity
was determined by analyzing the hydrolysates of a
Table 1. NMR Spectral Data of Compound 1(in CDCl
1 33.1 t2.70, 1.18
2 27.2 t1.68 (2H)
3 77.3 d3.27 dd (11.0, 4.8) C-28, C-29
4 39.0 s
5 51.2 d1.56 d(14.5) C-4, C-6, C-7, C-9, C-10,
C-19, C-28, C-29
6 36.6 t2.65, 2.54 C-5, C-7, C-8, C-10
7 199.0 s
8 145.6 s
9 151.7 s
10 40.3 s
11 193.9 s
12 79.1 d5.62 sC-11, C-13, C-14, C-18,
13 47.9 s
14 58.5 s
15 66.2 d4.80 t(8.5)
16 38.0 t2.75, 1.92
17 44.6 d2.54
18 12.1 q0.81 sC-12, C-13, C-14, C-17
19 17.9 q1.33 sC-1, C-5, C-9, C-10
20 29.4 d2.24
21 21.5 q0.97 d(6.5) C-17, C-20, C-22
22 48.5 t2.46, 2.30
23 206.1 s
24 46.6 t2.40, 2.80
25 35.1 d2.91
26 181.0 s
27 17.1 q1.17 d(6.5) C-24, C-25, C-26
28 27.8 q1.02 sC-3, C-4, C-5, C-29
29 15.5 q0.88 sC-3, C-4, C-5, C-28
30 21.2 q1.72 sC-8, C-13, C-14
CO 170.2 s
CO 20.9 q2.23 sCH
Anti-HIV agents from Ganoderma lucidum 1653
synthetic substrate in the presence or absence of the
isolated compounds using a HPLC method. Of the
tested compounds, 3and 7were found to be
the most active against HIV-1 PR with an IC
0.17 mM for both compounds. Other compounds
such as ganoderiol F (8), ganoderic acid C1 (4), 3b,
5a-dihydroxy-6b-methoxyergosta-7,22-diene (13),
ganoderic acid a(1), ganoderic acid H (5) and
ganoderiol A (6) inhibited the enzyme activity to a
similar extent (IC
=0.18±0.32 mM).
However, all compounds examined did not show
any inhibitory activity against another essential
enzyme, HIV-1-RT, at concentrations below
0.25 mM.
In the present experiment, we found that D
-lanostadiene-type triterpenes had relatively
strong anti-HIV-1 activity. On the other hand,
-lanostene-type triterpenes and ergostane-type
compounds 10±12 had no inhibition of HIV-1-
induced cytopathic eects.
As to HIV-1-protease, we could not obtain any
conclusive ®ndings on the structure-activity re-
lationship. Lanostane-type triterpenes showed IC
of 0.17±0.32 mM, while ergosterol derivatives had
no inhibitory activity. However, it was reported
that synthetic cosalane and its derivatives had an
anti-HIV-1 eect as well as inhibitory eects on RT
and PR [27]. Several triterpenes have been described
Fig. 2. (a) Proposed mass fragmentation pattern of 1. (b) Stereostructure for 1and 1a as indicated by
dierence NOE and NOESY spectra.
S. EL-MEKKAWY et al.1654
as antiviral compounds. Glycyrrhizin shows some
limited activity against a whole range of viruses
including HIV-1 [28]. Salaspermic acid [29] and sub-
erol (a lanostane-type) [30] inhibit HIV-1 in H9
cells in the upper micromolar range. Bile acid de-
rivatives are slightly active at 10
M against HIV-1
in MT-4 cells [31]. Betulinic acid derivatives
(lupane-type) have been described as potent inhibi-
tors of the cytopathogenicity of HIV-1 in CEM 4
and MT-4 cells without aecting HIV-1 RT or PR
activity [32]. When compared with other triterpenes
reported, compounds 8and 9can be used as leads
to develop other related compounds with potential
anti-HIV-1 activity.
Mps: uncorr. Optical rotations: in CHCl
soln at
20±268C. UV: in MeOH. IR: in KBr. EI-MS: ioniz-
ation voltage 70 eV.
H and
C NMR: 500 MHz
and 125 MHz, respectively.
Fruiting bodies of Ganoderma lucidum (Leyss. ex
Fr.) Karst. (Polyporaceae) were obtained from Alps
Chemical Industries Co. (Takayama, Japan) and
Linzhi General Institute of Co. Ltd. (Tokyo,
Japan), and their specimens were deposited at the
Museum of Materia Medica, Toyama Medical and
Pharmaceutical University (Toyama, Japan).
Enzymes and chemicals
Recombinant HIV-1 PR (purity 96% by SDS-
PAGE) was purchased from Bachem
Feinchemikalien AG (Bubendort, Switzerland).
Recombinant HIV-1-RT was obtained from Eiken
Chemicals Co. Ltd. (Osaka, Japan). A template-pri-
mer, (rA)
for the RT assay was obtained
from Pharmacia (Uppsala, Sweden). [Methyl-H
thymidine 5'-triphosphate (dTTP) (speci®c activity,
1.70 TBq mmol
) was obtained from Amersham-
Japan (Tokyo, Japan).
Isolation procedure
The chipped fruiting bodies of G. lucidum (5 kg)
was extracted with MeOH (3 20 l) at room temp.
to give 182 g of a solid extract. The MeOH extract
was suspended in 50% aq. MeOH (2 l), the organic
solvent was removed and ®ltered through a column
of Diaion HP-20 (2 l), washed with H
O and then
with MeOH. The MeOH eluate was evaporated in
vacuo to give 163 g of a solid extract. The MeOH
eluate (100 g) was chromatographed on silica gel,
and elution was started with hexane, CHCl
30% MeOH in CHCl
to give three fractions, fr. A
(18 g), fr. B (40 g) and fr. C (26 g). CC/silica gel
±EtOAc, 6:4) of fr. A (3 g) followed by
MPLC/silica gel (C
CO, 7:3) aorded 10
(365 mg), 11 (62 mg) and 13 (10 mg). Repeated CC
of fr. B (5 g) using silica gel (C
CO, 7:3),
RP-2 (40% aq. MeOH), MPLC/Si gel (C
CO, 7:3), and ®nally MPLC/silica gel (5%
MeOH in CHCl
) gave 4(8 mg), 5(9 mg), 8
(36 mg) and 9(16 mg). Similarly, repeated CC of fr.
C (4 g) yielded 1(40 mg), 2(43 mg), 3(47 mg), 6
(6 mg), 7(15 mg) and 12 (14 mg).
lanosta-8-en-26-oic acid (ganoderic acid a;1)
Amorphous powder, [a]
,c1.0). IR
max cm
: 3450 (OH), 1750 (carbonic acid C.O),
1730 (ester C.O), 1700 (C.O) and 1650sh (conju-
gated C.O). UV l
(log E) nm: 254 (3.8). EI-MS
m/z 574 [M]
, 532 [M ÿCH
, 514
[M ÿHOAc]
, 496 [M ÿHOAc ÿH
, 478
Table 2. Inhibitory Activities of Compounds from Ganoderma lucidum against
Protease and Proliferation of HIV-1
Compound IC (mg/ml) CC (mg/ml) IC
Ganoderic acid a(1) NE >1000 0.19
Ganoderic acid A (2) (1000) >1000 >1.0
Ganoderic acid B (3) NE >1000 0.17
Ganoderic acid C1 (4) NE >1000 0.18
Ganoderic acid H (5) NE >1000 0.20
Ganoderiol A (6) NE >1000 0.23
Ganoderiol B (7) (7.8) 500 0.17
Ganoderiol F (8) 7.8 15.6 0.32
Ganodermanontriol (9) 7.8 15.6 >1.0
Ergosterol (10) NE 1000 >1.0
Ergosterol peroxide (11) NE 15.6 >1.0
Cerevisterol (12) NE 31.3 >1.0
3b-5a-Dihydroxy-6b-methoxy ergosta-7,22-diene (13). NE 15.6 0.18
IC, the minimum concentration for complete inhibition of HIV-1 induced CEP in MT-4 cells by
microscopic observation. CC, the minimum concentration for appearance of MT-4 cell toxicity by
microscopic observation. NE, not eective. (), concentration at which weak anti-HIV-1 activity
was observed.
Anti-HIV agents from Ganoderma lucidum 1655
[M ÿHOAc ÿ2H
, 417 [a]
, 306 [g + H]
115 [e]
3b,15b-Diacetylganoderic acid a(1a)
Amorphous powder,
): d0.89
(3H, s,H
-18), 0.91 (3H, s,H
-29), 0.96 (3H, d,
J= 6.5 Hz, H
-21), 1.00 (3H, s,H
-28), 1.24 (3H,
-19), 1.24 (3H, d,J= 7.0 Hz, H
-27), 1.42
(3H, s,H
-30), 1.65 (1H, H-5), 2.05 (3H, s,CH
CO), 2.10 (3H, s,C
-CO), 2.25 (3H, s, CH
4.48 (1H, dd,J= 11.3, 4.9 Hz, H-3), 5.67 (1H, s,
H-12), 5.89 (1H, t,J= 8.4 Hz, H-15).
C NMR: d
68.9 (C-15), 79.9 (C-3), 80.0 (C-12), 146.1 (C-8),
154.4 (C-9), 170.0, 170.5 and 170.9 (3 acetoxyl
C1O), 179.6 (C-26), 191.9 (C-11), 207.5 (C-7) and
210.3 (C-23). EI-MS m/z 658 [M]
, 616
[M ÿCH
, 598 [M ÿHOAc]
, 538
[M ÿ2HOAc]
, 478 [M ÿ3HOAc]
, 390.
Reverse transcriptase assay
The assay was performed as previously
reported [33].
Protease assay
25 ml of HIV-1-PR assay buer (Bachem HIV-1
protease assay Kit S-100) containing 2.5 mgofa
substrate, His-Lys-Ala-Arg-Val-Leu-(pNO
, were mixed with 2.5 mlofa
DMSO soln of test compound, then 6.25 mlof
recHIV-1-PR (0.25 mg protein) was added to the
mixture. The reaction mixture was incubated for
15 min at 378C and then stopped by addition of
2.5 ml of 10% TFA. The hydolysate and remained
substrate were quantitatively analyzed by HPLC
under the following conditions: injection volume,
5ml; column, RP-18 (4.6 150 mm, Merck), elution,
a linear gradient of acetonitrile (20±40%) in 0.1%
TFA; ¯ow rate, 1.0 ml min
; detection, 280 nm.
The hydrolysate and substrate were eluted at 9.44
and 4.35 min, respectively. The inhibitory activity
of the compound in the HIV-1-PR reaction
was calculated as follows: %inhibition = 100
); where Ais a relative
peak area of the hydrolysate. Under the conditions,
acetylpepstatin was used as a positive control, its
being 0.30 mM.
The HTLV-I-carrying cell line MT-4 cells were
used. They were maintained at 378C under 5% CO
in RPMI-1640 medium (Flow Laboratories, Irvine,
Scotland), supplemented with 10% fetal calf serum
(FCS, Flow laboratories, North Ryde, Australia),
100 mgml
of streptomycin (Meiji Seika, Tokyo,
Japan) and 100 U ml
of penicillin G (Banyu
Pharmaceutical, Tokyo, Japan).
The LAV-1 strain of HIV-1 was obtained from
culture supernatant of MOLT-4 cells that had been
persistently infected with LAV-1.
Primary screening for anti-HIV-1activity
MT-4 cells were infected for 1 hr with HIV-1 at
of 0.001 per cell. Then, the cells were
washed and resuspended at 1 10
cells ml
RPMI-1640 medium. A 200 ml per well of the cell
suspension was cultured for 5 days in a 96-well cul-
ture plate containing various concentrations (12
doses, maximum 1000 mgml
and minimum
0.49 mgml
) of the isolated compounds. Control
assays were performed, without these compounds,
with HIV-1-infected and uninfected cultures. On
day 5, the IC of the test compound required to pre-
vent HIV-1-induced CPE completely was deter-
mined through an optical microscope and the cell
growth was examined to give the CC that reduces
the viability of MT-4 cells.
AcknowledgementsÐA part of this study was ®nan-
cially supported by Japan Health Science
Foundation (Tokyo, Japan) and Lingzhi General
Institute Co. (Tokyo, Japan).
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Anti-HIV agents from Ganoderma lucidum 1657
... Ganoderic acid α Anti-HIV protease (0.19 mM) G. lucidum [168] 15. 3-O-acetylganoderic acid B -G. lucidum [176] ...
... G. lucidum (fruit bodies) [168,214] 121. ...
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Mahesh C.A. Galappaththi, Nimesha M. Patabendige, Bhagya M. Premarathne, Kalani K. Hapuarachchi, Saowaluck Tibpromma, Dong-Qin Dai, Nakarin Suwannarach, Sylvie Rapior, Samantha C. Karunarathna. A review of Ganoderma triterpenoids and their bioactivities. Biomolecules, Special Issue Fungal Metabolism - Enzymes and Bioactive Compounds II, 13 (1), 24 (2023). doi:10.3390/biom13010024. hal-03912698 ___ For centuries, Ganoderma has been used as a traditional medicine in Asian countries to prevent and treat various diseases. Numerous publications are stating that Ganoderma species have a variety of beneficial medicinal properties, and investigations on different metabolic regulations of Ganoderma species, extracts or isolated compounds have been performed both in vitro and in vivo. However, it has frequently been questioned whether Ganoderma is simply a dietary supplement for health or just a useful "medication" for restorative purposes. More than 600 chemical compounds including alkaloids, meroterpenoids, nucleobases, nucleosides, polysaccharides, proteins, steroids and triterpenes were extracted and identified from Ganoderma, with triterpenes serving as the primary components. In recent years, Ganoderma triterpenes and other small molecular constituents have aroused the interest of chemists and pharmacologists. Meanwhile, considering the significance of the triterpene constituents in the development of new drugs, this review describes 495 compounds from 25 Ganoderma species published between 1984 and 2022, commenting on their source, biosynthetic pathway, identification, biological activities and biosynthesis, together with applications of advanced analytical techniques to the characterization of Ganoderma triterpenoids.
... Unlike plants, the use of mushrooms in traditional medicine is still unknown, yet they are very effective in the treatment of certain diseases in many regions of the world. Among the species used are species of the genus Trametes and species of the complex Ganoderma lucidum which are used in the treatment of cancer, diabetes, and AIDS (El-Mekkawy et al. 1998, Akbar & Yam 2011. Species of the G. lucidum complex are regarded as the most valuable medicinal mushrooms and used to treat various diseases (Paterson 2006, Grienke et al. 2014, Zhu et al. 2016. ...
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Wood-inhabiting fungi (WIF), such as polypores, are extremely species-rich and play vital roles in the functioning of forest ecosystems as decomposers. Despite the importance of polypores, our knowledge of the diversity and distribution of these fungi is still poor in general and especially for West Africa. To advance our knowledge we here summarise results from field collections between 2017 and 2021 and present (i) a taxonomic overview, (ii) phylogenetic placements and (iii) an illustrated catalogue of wood-inhabiting polypore fungi with colour pictures. During the field sampling campaigns, we collected 647 specimens. Based on morphological characteristics and molecular barcode data, 76 polypore species belonging to six orders, 15 families and 39 genera were identified. Of the 76 species, 30 are new to the West Africa, 69 new to Benin, and two new combinations Fuscoporia beninensis and Megasporia minuta are proposed. With this summary, we provide new data for further research.
... Triterpenes isolated from Ganoderma species such as G. lucidum have been identified as potent anticancer and immunomodulatory agents Nonaka et al.; Cheng et al. and Watanabe et al. [58][59][60]. Some triterpenes, namely, ganoderic acid C and derivatives from G. lucidum are able to inhibit biosynthesis of cholesterol Wu et al. [56]; contribute to atherosclerosis protection Komoda et al. [61]; and also show antiviral, antibacterial activity Morigiwa and el-Mekkawy [62,63]. Different sterols of fruit bodies of Inonotus obliquus were recorded with anti-inflammatory properties Niedermeyer et al. and Park et al. [64,65]. ...
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Objective: Mushrooms have been valued as traditional sources of natural bioactive compounds for many centuries and targeted as promising therapeutic agents. The bioactive mycomolecules of mushrooms are reported to have antioxidant, antitumor, antidiabetic, anti-inflammatory, and antimicrobial activity, which are the important medicinal targets in terms of drug discovery today. Hence, an attempt was made in the present study, to evaluate the immunomodulatory and oxidative process of secondary metabolites from the milky mushroom Calocybe indica (P&C) var.APK2 using radical scavenging assays. Methods: The fruiting bodies of milky mushrooms were found to produce an array of mycomolecules such as phenols, flavonoids, alkaloids, tannins, terpenoids, steroids, and saponins in their methanolic extract which was confirmed using Fourier-transform infrared spectrophotometer (FT-IR) analysis and standard phytochemical studies; hence, chromatography fractions of these mushroom seem greatly promising biological activities including antioxidants. Results: The functional analysis of the secondary metabolites of these macrofungi was evaluated by the separation of potential fractions using preparative thin-layer chromatography (TLC) that revealed seven distinct bands with Rf values of 0.14, 0.26, 0.31, 0.42, 0.52, 0.70, and 0.82; the antioxidant activity was determined through TLC in situ bio autography. The quenching property of metabolite compound which was ranging from 19% to 77.9% and the half effective concentration values of 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radical scavenging activity was recorded as 64.26 μg/ml and 54.5 μg/ml sample concentration, respectively. The active mycomolecules of C. indica from the TLC was, further, confirmed using Gas Chromatography–Mass Spectrometry studies. Conclusion: The present investigation of the study revealed that the antioxidant efficacy of edible milky mushroom may be further proceeded for in vivo studies for novel drug discovery.
... Solo en las últimas décadas este organismo se ha venido investigando de manera sistemática en la medicina occidental y oriental, lo que ha permitido encontrar gran cantidad de compuestos y metabolitos activos con efectos biológicos, los cuales son obtenidos a través del cultivo de G. lucidum. Estos compuestos son principalmente los polisacáridos β-(1-3)-glucanos y β-(1-6)-glucanos (Daniel 2004, Huie y Di 2004, Yang et al. 2010, los triterpenos como los ácidos ganodéricos A, B, T y Me (Gao et al. 2002, Hirotani et al. 1987, Hirotani et al. 1985, Tang et al. 2006, entre otros componentes, los cuales presentan alta actividad fisiológica-metabólica reflejada en una creciente evidencia científica, destacándose las siguientes propiedades: antihepatitis (Campos et al. 2006, Lin 2005, Lin et al. 2003, antiinflamatoria (Akihisa et al. 2007, Ko et al. 2008, Patocka 1999, anti-HIV (El-Mekkawy et al. 1998, Min et al. 1998, hipoglucemiante (Hikino et al. 1989), hipocolesterolémica (Berger et al. 2004, Hajjaj et al. 2005, antiandrogénica (Liu et al. 2007), hepatoprotectora (Zhang et al. 2002), actividad antitumoral y anti-angiogénesis (Cao y Lin 2004, Chen et al. 2004, Song et al. 2004, Stanley et al. 2005) e inmunomoduladora (Lin 2005, Liu et al. 2003). ...
Se evaluó el efecto de los campos eléctricos sobre el crecimiento del hongo Ganoderma lucidum [(W. Curt.: Fr.) P. Karst. Ganodermataceae] bajo condiciones de cultivo sumergido, con el objetivo de optimizar su producción de biomasa. Ganoderma lucidum fue expuesto a tres factores diferentes [tipo de campo eléctrico corriente alterna (AC), corriente continua (DC) y corriente pulsada (IM)]; intensidad del campo [siete intensidades de campo desde 0,0 kV cm-1] (cultivo control) hasta 3,0 kV cm-1; y periodo de estimulación [dependiendo de la fase de crecimiento del hongo, después de la inoculación día 0 (fase lag), día 3 (fase exponencial o log) y día 6 (fase estacionaria)]. Los resultados mostraron que la combinación del campo eléctrico AC, con una intensidad de 1,5 kV cm-1 y aplicado al día 3 presentaron una mejor producción de biomasa con una media de 35,6450 ± 0,6684 g l-1, mientras que la combinación de los tres factores tipo de campo eléctrico DC a una intensidad de 2,5 kV cm-1 y aplicado el día 6 presentaron una menor producción de biomasa con una media de 26,2950 ± 3,9926 g l-1. Los anteriores resultados muestran que según la combinación de los factores evaluados es posible estimular la producción de biomasa del hongo Ganoderma lucidum bajo condiciones de cultivo sumergido mediante la aplicación de campo eléctrico.
... Suwannarach, et al. [13] reviewed literatures on fungi as producers of protease inhibitors and bioactive compounds that can offer immunomodulatory activities as potential therapeutic agents of coronaviruses. El-Mekkawy, et al. [67] and Min et al [68] isolated and characterized some triterpenes called ganoderic acids from G. lucidum that were inhibitory to HIV-1. Protease inhibitors play an important role in viral replication by selectively binding to viral proteases and blocking proteolytic cleavage of the protein precursors that are necessary for the production of infectious viral particles [13]. ...
The novel coronavirus (SARS-CoV-2) emerged in Wuhan, China in December 2019 causing the coronavirus disease 2019 (COVID-19). The disease has caused a pandemic that had disrupted social and economic life globally. Intense research is ongoing to understand the nature of the virus and pathogenesis as well as the development of drugs and vaccines. Ample evidence suggests that the elderly people, those with pre-existing chronic medical conditions, such as lung disease, heart disease, diabetes, obesity, chronic kidney disease, compromised immunity and even men may be at higher risk of serious illness and intensive care. The virus tends to trigger the over-production of pro-inflammatory cytokines, which results in multiorgan damage, resulting in death. Following this review, we proposed the use of Ganoderma mushroom extracts, which have certain properties relevant to the management of COVID-19 complications including anti-inflammatory, antiviral, immune modulatory, and antioxidant, anti-aging and multiorgan protection. Most of this research has been done on rodent models with few clinical trials. Since, the mushroom is generally regarded as safe (GRAS) and have been used for centuries in Asian traditional medicine, we recommend the use of this mushroom in the management of the disease including as active ingredients in COVID-19 drugs, and alternatives to synthetic drugs, health supplements, adjuvant therapy or functional foods.
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Ganoderma lucidum (G. lucidum, Lingzhi) is a well-known herbal medicine with a variety of pharmacological effects. Studies have found that G. lucidum has pharmacological effects such as antioxidant, antitumor, anti-aging, anti-liver fibrosis, and immunomodulation. The main active components of G. lucidum include triterpenoids, polysaccharides, sterols, peptides and other bioactive components. Among them, the triterpenoids and polysaccharide components of G. lucidum have a wide range of anti-liver fibrotic effects. Currently, there have been more reviews and studies on the antioxidant, antitumor, and anti-aging properties of G. lucidum. Based on the current trend of increasing number of liver fibrosis patients in the world, we summarized the role of G.lucidum extract in anti-liver fibrosis and the effect of G. lucidum extract on liver fibrosis induced by different pathogenesis, which were discussed and analyzed. Research and development ideas and references are provided for the subsequent application of G. lucidum extracts in anti-liver fibrosis treatment.
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Ganoderic acids (GAs) are well recognized as important pharmacological components of the medicinal species belonging to the basidiomycete genus Ganoderma . However, transcription factors directly regulating the expression of GA biosynthesis genes remain poorly understood. Here, the genome of Ganoderma lingzhi is de novo sequenced. Using DNA affinity purification sequencing, we identify putative targets of the transcription factor sterol regulatory element-binding protein (SREBP), including the genes of triterpenoid synthesis and lipid metabolism. Interactions between SREBP and the targets are verified by electrophoretic mobility gel shift assay. RNA-seq shows that SREBP targets, mevalonate kinase and 3-hydroxy-3-methylglutaryl coenzyme A synthetase in mevalonate pathway, sterol isomerase and lanosterol 14-demethylase in ergosterol biosynthesis, are significantly upregulated in the SREBP overexpression (OE::SREBP) strain. In addition, 3 targets involved in glycerophospholipid/glycerolipid metabolism are upregulated. Then, the contents of mevalonic acid, lanosterol, ergosterol and 13 different GAs as well as a variety of lipids are significantly increased in this strain. Furthermore, the effects of SREBP overexpression on triterpenoid and lipid metabolisms are recovered when OE::SREBP strain are treated with exogenous fatostatin, a specific inhibitor of SREBP. Taken together, our genome-wide study clarify the role of SREBP in triterpenoid and lipid metabolisms of G. lingzhi .
Medicinal plants are always acceptable for their activity towards different disease targets as they contain various extractable chemical constituents and bioactive metabolites. Plant products have been showing their unexpected activities towards different point of our life since the very first day of civilization. During metabolism process, plants produce different chemical compounds including different secondary metabolites that are not involved in the direct growth or development of the plant but in protection of the plant from different outside as well as inside enemies. Those secondary metabolites such as polyphenols, alkaloids, flavonoids, tannins, sapogenins are having different biological activities towards different diseases conditions in human body. Hundreds of secondary metabolites from different plants have been tested preclinically as well as clinically and gave excellent action against different disease such as inflammation, diabetic, carcinogenesis, depression, cytotoxicity, hepatotoxicity, microbial infection including viral infections as HIV. This chapter is mainly focused on different activities of different secondary metabolites and their mechanism of actions in different stages of the life cycle of HIV and its infection in human body including some reported compounds with potent activity. Papaverine, Apocynin, Taxifolin, Mangiferin, Genomycin I including Calanolide A, Suksdorfin, Bevirimat, etc. are well-known compounds from different natural sources that showed very potent activities in different conditions of HIV infection.
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Triterpenoids, important secondary plant metabolites made up of six isoprene units, are found widely in higher plants and are studied for their structural variety and wide range of bioactivities, including antiviral, antioxidant, anticancer, and anti-inflammatory properties. Numerous studies have demonstrated that different triterpenoids have the potential to behave as potential antiviral agents. The antiviral activities of triterpenoids and their derivatives are summarized in this review, with examples of oleanane, ursane, lupane, dammarane, lanostane, and cycloartane triterpenoids. We concentrated on the tetracyclic and pentacyclic triterpenoids in particular. Furthermore, the particular viral types and possible methods, such as anti-human immunodeficiency virus (HIV), anti-influenza virus, and anti-hepatitis virus, are presented in this article. This review gives an overview and a discussion of triterpenoids as potential antiviral agents.
The structures of eight novel triterpenoids, ganoderiol C (1), D (2), E (3), F (4), G (5), H (6), I (7), and ganolucidic acid E (8), isolated from the fruiting body of Ganoderma lucidum were determined by spectroscopic methods. In addition, the absolute configuration at C-23 of ganolucidic acid D (9) was determined from the CD spectrum of its p-imethylaminobenzoate derivative. © 1988, Japan Society for Bioscience, Biotechnology, and Agrochemistry. All rights reserved.
Seven new triterpenes, ganoderic acids F, G, and H, lucidenic acids D2 and E2, compound C5’, and compound C6, were isolated from the surface part of gills of Ganoderma lucidum. The structures 3a, la, 4a, 6a, 7a, 2b, and 5b were proposed for these compounds, respectively. Detailed analyses of the proton and carbon-13 nuclear magnetic resonance (¹H- and ¹³C-NMR) spectra were performed by using two-dimensional (2-D) ¹H—¹H and ¹H-¹³C shift correlation techniques. © 1986, The Pharmaceutical Society of Japan. All rights reserved.
Sixteen new triterpene acids isolated as the methyl esters from the gills of Ganoderma lucidum (Polyporaceae) along with five known triterpenes. The structures of seven new compounds among them, ganoderic acids C2, E, I, and K, compounds B8 and B9 and lucidenic acid F, were elucidated. Detailed analyses of their proton and carbon-13 nuclear magnetic resonance (1H- and 13C-NMR) spectra were also done by application of two-dimensional NMR techniques.
Two new lanostane-type triterpenoids, ganoderiol A (1) and ganoderiol B (2) were isolated from the fruiting bodies of Ganoderma lucidum, together with known ganodermanontriol (3) and ganodermatriol (4). The compounds were identified as 5∝-lanosta-7, 9(ll)-dien-3β, 24, 25, 26-tetraol (1), 15a, 26, 27-trihydroxy-5α-lanosta-7, 9(11), 24-trien-3-one (2), 24, 25, 26-trihydroxy-5α-lanosta7, 9(1l)-dien-3-one (3) and 5α-lanosta-7, 9(11), 24-trien-3β, 26, 27-triol (4), respectively.
New highly oxidized lanostane-type triterpenoids, ganoderic acid D, E, F, and H and lucidenic acid D, E, and F, were isolated from the gills of Ganoderma lucidum and their structures were elucidated on the basis of spectral evidence.
Four new highly oxidized lanostane-type triterpenoids, ganoderic acid G and I and ganolucidic acid A and B, were isolated from the fungus ganoderma lucidum and their structures were elucidated on the basis of spectral evidence.
Ganoderic acid C, a new lanostane-type triterpenoid was isolated from the fruit body of Ganoderma lucidum. The structure of ganoderic acid C was elucidated by spectroscopic data and X-ray analysis of methyl ganoderate C acetate.