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Characterisation of Extracts and Anti-Cancer Activities of Fomitopsis pinicola

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Fomitopsis pinicola (Sw. Karst) is a common bracket fungus, with a woody texture. It is found predominantly in coniferous forests in temperate regions throughout Europe and Asia. Fomitopsis pinicola has been extensively used for medicinal purposes, particularly in Chinese and Korean traditional medicine. In this mini-review, the anti-cancer characteristics of F. pinicola extracts were investigated. In vitro experiments revealed the pro-apoptotic, anti-oxidant and anti-inflammatory properties of extracts, whilst two of three in vivo studies reported an inhibition of tumour growth and prolonged survival. Only studies wherein fungal specimens were sourced from Europe or Asia were included in this review, as samples sourced as F. pinicola from North America were probably not F. pinicola, but a different species. Although not one of the most revered fungal species, F. pinicola has been used as a medicinal fungus for centuries, as well as consumed as a health food supplement. To date, the results from only three in vivo studies, investigating anti-cancer properties, have been published. Further studies, using comprehensively identified specimens, are required to fully elucidate the anti-cancer properties of F. pinicola extracts.
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Nutrients 2020, 12, 609; doi:10.3390/nu12030609
Characterisation of Extracts and Anti-Cancer
Activities of Fomitopsis pinicola
Karen S. Bishop *
Discipline of Nutrition and Dietetics/Auckland Cancer Society Research Centre, School of Medical Sciences,
Faculty of Medicine and Health Sciences, University of Auckland, 85 Park Road, Grafton,
Auckland 1023, New Zealand;; Tel.: +64-9-923-4471
Received: 23 January 2020; Accepted: 24 February 2020; Published: 26 February 2020
Abstract: Fomitopsis pinicola (Sw. Karst) is a common bracket fungus, with a woody texture. It is
found predominantly in coniferous forests in temperate regions throughout Europe and Asia.
Fomitopsis pinicola has been extensively used for medicinal purposes, particularly in Chinese and
Korean traditional medicine. In this mini-review, the anti-cancer characteristics of F. pinicola extracts
were investigated. In vitro experiments revealed the pro-apoptotic, anti-oxidant and anti-
inflammatory properties of extracts, whilst two of three in vivo studies reported an inhibition of
tumour growth and prolonged survival. Only studies wherein fungal specimens were sourced from
Europe or Asia were included in this review, as samples sourced as F. pinicola from North America
were probably not F. pinicola, but a different species. Although not one of the most revered fungal
species, F. pinicola has been used as a medicinal fungus for centuries, as well as consumed as a health
food supplement. To date, the results from only three in vivo studies, investigating anti-cancer
properties, have been published. Further studies, using comprehensively identified specimens, are
required to fully elucidate the anti-cancer properties of F. pinicola extracts.
Keywords: anti-cancer properties; extracts; Fomitopsis pinicola; location; medicinal history; sequence
identification; taxonomy
1. Introduction
Fomitopsis pinicola (Sw. Karst), is a common woody fungus found in coniferous forests in
temperate regions throughout Europe and Asia [1], including the Himalayas [2]. Numerous local
names exist for F. pinicola, such as the Japanese name, which is Tsugasaruno-koshikake [3], and the
English name of red-belted bracket fungus [4]. Fomitopsis pinicola is commonly known as a brown-rot
fungus, characterised by bipolar sexual compatibility and the presence of the phenol oxidase,
tyrosinase (with extracellular oxidase not present) [3]. It has been used in Chinese and Korean
traditional folk medicine as an anti-inflammatory agent and for general well-being.
The fruiting body is fan shaped, has a hard, woody texture, can grow up to 40 cm in diameter
(Figure 1), and is often referred to as the red belt conk. The fruiting body has a glossy appearance and
can be red-brown or a lighter colour depending on the age of the specimen. It grows by adding an
additional layer or tube annually. The fungus is saprobic and can also be parasitic, causing heart rot
in living trees, and brown cuboidal rot in dead trees [2]. Decay fungi such as F. pinicola are often
thought to be symbiotic and this could be due to the presence of fungi and nitrogen fixing bacteria at
the same sites on fir trees [5]. In addition, they help circulate forest nutrients through the decay of
dead tree trunks, although the brown rot residues can remain in the soil for extended periods before
breaking down [6,7]. However, F. pinicola and other brown rot species can also contribute
significantly to forestry loses, particularly at sites where the bark has been damaged as might occur
when branches are removed.
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Fomitopsis pinicola, like many other fungi, are predominantly identified phenotypically, but
require molecular biology techniques to confirm the identification. Internal spacer region (ITS)2
sequencing is a suitable method that is routinely used for the correct identification of numerous
species, including F. pinicola. Unfortunately, it can appear phenotypically similar to Ganoderma lingzhi
and other species of the genus Fomitopsis, and therefore it is important to confirm the speciation of
the specimen one is working with prior to publication.
A literature review of the anti-cancer properties of F. pinicola was performed using Embase, Web
of Science and Google Scholar. Articles, published in English, where an in vitro and/or in vivo
approach was implemented to investigate the anti-cancer properties of F. pinicola extracts, were
included. Due to extensive fungal species misidentification [8], taxonomy and means of accurate
identification of F. pinicola were also explored. Search terms included “Fomitopsis pinicola”+ “cancer”
+ “in vivo.” Thereafter “anti-inflammatory” was substituted for “cancer”, and an additional article was
returned. In a similar manner “in vitro” was substituted for “in vivo”, and “Fomitopsis pinicola” +
“taxonomy” were also searched. Pearly growing was implemented. This article is not a systematic
review and, together with the implementation of pearly growing, it was decided not to include numbers
and justification for article inclusion and exclusion.
2. The Taxonomy of F. Pinicola
Fungi are poorly, and sometimes incorrectly, described [8]. More recently, sequence-based
classification and identification (SBCI) has been used to detect and classify environmental fungi and
also to confirm or dispute identification or classification of named specimens. The ITS of rRNA genes
can be PCR-amplified and sequenced, and this method is commonly used for SBCI [8]. Further, 16S
rRNA sequences may also be used for this purpose, but it is regarded as less accurate than ITS
sequencing, as the latter is less highly conserved and is therefore more likely to vary from one species
to another [9]. To help avoid misidentifications, Edgar recommends the sequencing of two rather
than one variable region, which could include V3, V4, V5 and ITS, or full-length 16s rRNA or large
subunit rRNA genes [8,9]. With the integration and standardisation of stand-alone databases, and the
incorporation of phylogenetic trees into pipelines used to identify or name specimens, data will be
easier to incorporate into databases and therefore more likely to be deposited, and easier to access,
thus strengthening the accuracy of fungal identification [8].
F. pinicola, an ancient polypore species, is classified according to the Integrated Taxonomic
Information System [10] as follows:
Kingdom: Fungi
Division: Basidiomycota
Class: Agaricomycetes
Order: Polyporales
Family: Fomitopsidaceae
Genus: Fomitopsis
Species: F. pinicola
Fomitopsis pinicola was originally named in 1810 as Boletus pinicola by Swartz and then transferred
to Fomitopsis by Petter Karsten in 1881 [11,12]. Fomitopsis pinicola (Swartz ex Fr.) P. Karst. (1881) was
also named as Polyporus pinicola Fr. [3] before sequencing was used to clearly define the species. More
recently, Binder et al. performed whole-genome sequencing using a shotgun approach, and classified
F. pinicola in the antrodia clade [7].
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Figure 1. Basidomes of Fomitopsis pinicola in situ. These specimens were identified as F. pinicola by
internal spacer region 2 sequencing [13]. (Permission was obtained from NZFocus to utilise this image.)
In 2016, Haight et al. reported on an investigation into the suspected F. pinicola complex [14].
Based on samples collected in North America, Europe and Asia and phenotypically identified as F.
pinicola, four distinct species were identified, with only F. pinicola found in Europe and Asia. The
other three species were found in different regions of North America [1,14]. For this reason, articles
based on samples collected outside of Europe and Asia were not included in this review article.
F. pinicola is widely available and has been extensively used for medicinal purposes, particularly
in Chinese traditional medicine [15]. However, the use of F. pinicola in Central European folk
medicine has been largely forgotten [16]. Like many hardwood bracket fungi, it is believed that F.
pinicola specimens were traditionally prepared for consumption as a soup/tea or in alcohol [15].
Although not one of the most revered fungal species, F. pinicola (Sw Karst) has been used as a
medicinal fungus for centuries for the treatment of headaches, nausea and liver disease [16], as well
as in health food supplements [15,16].
3. Active Ingredients
For centuries, medicinal mushrooms have been used by various cultures to enhance health.
Pharmacologic research into medicinal mushrooms, using in vitro, in vivo and clinical studies, has
been used to identify several health benefits and their associated biological pathways [17]. However,
very little research has been carried out on F. pinicola. A variety of extraction methods, whole extracts,
fractions and compounds isolated from the mushroom, have been tested. Many of these are listed in
Table 1. Studies carried out on specimens sourced from North America were not include (e.g., Liu et
al. [18])
Table 1. Extraction method and fraction or compound detected from F. pinicola specimens.
Citation Extraction method Details of method Fraction/Compound/Concentration
Gao et al. 2017,[19]
95% ethanol or
methanol for 8 to
10 hours at room
evaporated and
washed in water,
evaporated and
0.210 µM GAE/mg
Hot water
Heated at 100 °C
for 2 to 3 hours; 4
°C overnight;
centrifuged and
0.185 µM GAE/mg
Ethyl acetate NT. 0.464 µM GAE/mg
Petroleum ether NT. 0.389 µM GAE/mg
Wu et al. 2014, [20] Ethanol
Extracted three
times with 50%
ethanol or water
for 24 h. The
solutions were
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filtered, the solvent
removed by
distillation and the
sample was
Gao et al. 2017, [19] Chloroform/ethanol
The specimens
were dried and
milled. Thereafter,
the powder was
homogenised in
95% ethanol at 45
°C and subjected to
ultrasonic- assisted
extraction. The
extract was
fractionated with
homogenised in
centrifuged and the
supernatant was
Ergosterol (105 µg/mg)
Pachymic acid (35.6 µg/mg)
Dehydroeburicoic acid (2.5 µg/mg).
Kao, 2019;
Kao et al. 2018;
Kao et al. 2016, [13,21,22]
Whiskey/Rice wine
Submerged in
whiskey or rice
wine for six
months, then
freeze dried. The
whiskey extract
was fractionated
1:1:1:1 (water:
methanol: ethanol:
Aqueous fraction
Organic fraction
(56.4% and 43.6% total weight
Yoshikawa et al. 2005, [23] Ethanol
Submerged in 70%
ethanol for six
weeks and
separated into
EtOAc and H2O
Thereafter, the
EtOAc extract was
fractionated using
silica gel column
and some fractions
were further
fractionated using
an HPLC.
Lanostane triterpenes: Fomitopinic
acid A and B
Lanostanoid glycosides: Fomitoside
Keller et al. 1996, [24] Dichloro-methane
Seven triterpenes.
-8,24-dien-21-oic acid,
polyporenic acid C,
oic acid,
21-hydroxylanosta-8,24-dien- 3-one,
pinicolic acid A,
trametenolic acid B
and pachymic acid21-oic acid
EtOAc—Ethyl acetate; GAE—gallic acid equivalents; HPLC—high-performance liquid
chromatography; NT—not tested.
Although Table 1 includes the compounds that were detected in F. pinicola using different
extraction methods, the anti-cancer activities were not assessed. Various phytochemicals have been
shown to have specific anti-cancer properties, but it is generally accepted that these compounds
Nutrients 2020, 12, 609 5 of 9
probably act synergistically to achieve an anti-cancer effect [25]. Wang et al. identified ergosterol in
a chloroform extract from F. pinicola and observed anti-cancer properties such as a pro-apoptotic and
inhibition of migration effects [26]. Further, in a study published by Yoshikawa et al., fomitopinic
acids and fomitosides inhibited cyclooxygenase (COX) 1 and 2 activity [23]. Although many of the
compounds detected in F. pinicola have not been assessed in isolation, some of the compounds have
been isolated from other species and found to have anti-cancer properties e.g., gallic acid [27]. Based
on the available evidence, it is not possible to determine exactly which compounds exert the strongest
anti-cancer properties, and further research is required.
4. Anti-Cancer Activities
Medicinal properties of mushrooms, based on hearsay, have been recorded for thousands of
years—for example, Ganoderma lucidum (Lingzhi) has been used for general well-being since before
the 5th century by the Chinese [28]; Formes fomentarius has been used as a potent anti-inflammatory
agent by the Greeks (450 BC) [29]; and puffball mushrooms of the genus Calvatia, have been used for
centuries by Native Americans to promote wound healing [29]. More recently, medicinal mushrooms
have been used as an adjuvant to cancer therapy to enhance the effects of treatment and for the
alleviation of side effects from chemo- and radiation therapy (e.g., nausea) [30]. Furthermore,
numerous clinical trials have been conducted to assess the potential anti-cancer properties of both in-
house and commercially prepared medicinal mushrooms [30]. Fewer than ten in vitro studies on
cancer cell lines have been published, but the number of in vivo publications on F. pinicola are even
more limited.
4.1. In Vitro Studies
Numerous cell culture experiments have been used to investigate the anti-cancer properties of
F. pinicola extracts. These studies have been outlined in Table 2.
Table 2. In vitro studies in which the anti-cancer properties of F. pinicola were investigated.
Citation Cell line* Cancer
Type of
IC50+ Outcomes
Choi et al. 2007, [31]
N/A N/A Not specified N/A N/A
Increased anti-oxidant
HeLa Cervix Water
HO-1 Melanoma Water
SNU-354 Liver Water
SNU-185 Liver Water
Hep3B Liver Water
Hep3B Liver Water
PLC/RF/5 Liver Water
Wu et al.2014, [20]
(mouse) Sarcoma Water
Increased CC3, APAF-1
and C-PARP
HepG2 Hepatoma Water
Increased CC3; NT; NT
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A549 Lung Water
Increased CC3; NT; NT
HCT-116 Colon Water
Increased CC3; NT; NT
MB-231 Breast Water
Increased CC3; NT; NT
Gao et al. 2017, [19]
(mouse) Sarcoma FPKc NT 36.2
Induced late stage
apoptosis/decrease in
MMP/DNA fragmentation
HL-60 Leukemia FPKc NT 41.0 NT
K562 Leukemia FPKc NT 98.9 NT
U937 Leukemia FPKc NT 34.9 NT
7721 Hepatoma FPKc NT 246.2 NT
Eca-109 Esophageal FPKc NT 169.7 NT
Wang et al. 2014, [26]
SW-480 Colon FPKc NT 190.3
Inhibits cell migration and
induce apoptosis.
SW-640 Colon Ergosterol
NT 143.3 Induced cell apoptosis
Kao et al. 2018;
Kao et al. 2016
PC3 Prostate WhE NC NT
Upregulation of pro-
apoptotic genes, and
down-regulation of anti-
apoptotic genes.
Significant changes in
gene expression associated
with cell-cycle pathways,
amongst others.
DU145 Prostate WhE NC NT
Significant changes in
gene expression associated
with cell-cycle pathways,
amongst others.
Yoshikawa et al. 2005, [23] N/A N/A
acid and
Anti-inflammatory activity
in response to COX 1 and
*All cell lines are of human origin, unless otherwise stated. + IC50 was measured at 72 h in µg/ml.
Abbreviations: APAF1-apoptotic peptidase activating factor 1; CC3—cleaved caspase 3; COX-
cyclooxygenase; C-PARP—cleaved-poly ADP ribose polymerase; FPKc—F. pinicola chloroform
extract; IC50—half maximal inhibitory concentration; MMP—mitochondrial membrane potential;
N/A-not applicable; NC—not comparable (reported in µl); NT—not tested/not reported; WhE—
whiskey extract.
Hanahan and Weinberg described various hallmarks of cancer [32], which have enabled us to
study the impact of extracts/compounds on these hallmarks (e.g., evasion of programmed cell death)
and their related pathways, rather than on cancer directly. Underlying these hallmarks are
mechanisms such as inflammation, genome instability and the creation of a tumour
microenvironment [32]. Many of the in vitro studies outlined in Table 2 showed an increase in anti-
oxidant activity[31], increase in apoptosis [19,26] or an upregulation of pro-apoptotic genes [21,22],
and anti-inflammatory activity [23]. In addition, PARP, which is involved in DNA repair, genomic
Nutrients 2020, 12, 609 7 of 9
stability and programmed cell death, increased in response to treatment in a sarcoma cell line [20].
Cell cycle dysregulation is another hallmark of cancer [32] and may be a target of the mechanism of
action of FPKc. This reasoning is supported by in vitro evidence showing the inhibition of cell
proliferation; damage to cell membrane in sarcoma but not healthy cells; the triggering of S-phase
cell cycle arrest; a decrease in MMP and release of mitochondrial cytochrome C [19]. Together, these
in vitro studies show that F. pinicola extracts/compounds have anti-cancer activities which warrant
further investigation.
4.2. In Vivo Studies
A small number of in vivo studies have been performed wherein the anti-cancer properties of F.
pinicola were investigated. These studies are listed in Table 3. In two of the studies S-180 sarcoma cells
were used to induce a xenograft [19,20], and in the remaining study, PC3 prostate cancer cells were
used [13]. The extracts (ethanol and chloroform) were both active against the sarcoma xenograft and
inhibited growth, but the powder obtained from an F. pinicola ethanol extract showed no activity
against the prostate cancer xenograft. The discrepancy in the results is thought to be due to the lack
of bioavailability of the ethanol powder extract, as well as treatment at a later stage of disease [13].
In addition to the three studies described in Table 3, Choi et al. also carried out an animal
experiment whereby rats received 0.83 g/kg of mushroom for two weeks following the administration
of ethanol for two weeks [31]. Glutathione, glutathione peroxidase and catalase were all found to be
significantly higher in the intervention versus the control group [31]. Glutathione is an anti-oxidant
and, together with glutathione peroxidase and catalase, protects the cell against oxidative damage,
and thus can exert an anti-tumour effect.
Table 3. In vivo studies in which the anti-cancer properties of F. pinicola were investigated.
Citation Study
design Treatment Type of
Delivery of
extract Outcomes
Wu et al.2014, [20]
Balb/c male
mice with
1.5–5 g/kg; 3
and 7 days
prior to
Inhibition of tumour growth
(growth inhibitory ratio = 54%
compared to control) and
prolonged survival (40%
survival in the control group,
and 60%–70% survival in the
intervention groups at day 30).
Gao et al. 2017, [19]
ICR mice
with S180
200 mg/kg; 7
days prior to
FPKc Inoculated
Inhibition of tumour growth
(inhibition rate = 47.7%
compared to control) and
prolonged survival (control
group–survival ranged from 12
to 15 days, and the intervention
group, survival ranged from 15
to 19 days.
Kao, 2019, [13]
Rag-1 male
mice with
1 g/kg once
the tumour
had reached
200 mm3
extract as a
Oral gavage Dose was tolerated. No
noticeable effect.
Abbreviations: FPKc—chloroform extract of F. pinicola; ICR—institute of cancer research.
In a rat model with diabetes induced by streptozotocin, F. pinicola treatment decreased glucose
levels, restored insulin levels to nearly normal, and pancreatic tissue damage was ameliorated [33].
The alkali extract was more effective than the water extract at reducing the harmful effects of
streptozotocin induced diabetes [33]. Enhanced glucose uptake, and therefore hyperglycaemia, is a
metabolic characteristic of cancer cells, and therefore the link between diabetes and cancers [34] is not
surprising. Although the in vivo study by Lee et al. focused on the impact of F. pinicola extracts on
diabetes, the benefits could be extrapolated to the treatment of cancers. This hyperglycaemic effect,
in the context of cancers, should be investigated further.
Nutrients 2020, 12, 609 8 of 9
4. Limitations
The most obvious limitation of this review is the lack of certainty surrounding the identity of the
specimens used in the studies we discuss. For example, Gao et al. 2017 state that F. pinicola is
traditionally categorized as Reishi [19], yet Reishi is identified as Ganoderma lucidum (Lingzhi) [28]. It
is therefore unclear as to whether Gao et al. studied G. lucidum or F. pinicola and the method of species
identification is not stated.
Another limitation includes the small number of in vivo studies performed. The fact that only
three in vivo studies have been carried out, whereby the anti-cancer properties of F. pinicola were
investigated, indicates the paucity of data and the need to carry out further studies in different cancer
5. Conclusions
In conclusion, further research is required to characterise the anti-cancer activities of F. pinicola
as there is a paucity of data, particularly from in vivo and clinical studies. It would be useful to
identify the bioactive components of F. pinicola and build on the research performed by Wang et al.
and Gao et al. [19,26]. In particular, care must be taken to correctly identify each specimen using
molecular techniques, prior to experimentation. Like many food components, F. pinicola has the
potential to reduce the risk of disease. The advantage of investigating the anti-cancer benefits of F.
pinicola is that the mushroom is not toxic as shown by anecdotal evidence over centuries, as well as
in vivo studies. In addition, it is widely available and is affordable.
Funding: This research received no external funding
Acknowledgments: Proof reading by Renee Alumasa is acknowledged and appreciated.
Conflicts of Interest: The author declares no conflict of interest.
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... This species damages timber, causing brown wood rot. At the same time it is used in traditional medicine in Siberia, China and Korea (Bishop 2020, Gründemanna et al. 2020. ...
... For alkaline extracts, the antidiabetic effect has been demonstrated in rats (Lee et al. 2008), as well as an immunomodulating, anti-inflammatory and antioxidant effects of its polysaccharides. It has been shown that fruit bodies contain ergosterol, sesquiterpenes, lanostane triterpenes and their glycosides (Bishop 2020, Janardhanan et al. 2020. Moreover, fungi fruit bodies are rich in phenolics which are known as the powerful reducing agents, and other biologically active substances -anthroquinones, carbohydrates, amino acids (Ermoshin et al. 2021a). ...
... The studied species was found mainly on pine. However, the species is also known to inhabit deciduous species, including birch, but with a significantly lower abundance (Bishop 2020, Gründemanna et al. 2020. The biomass and the number of collected fruit bodies are presented in Table 1. ...
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Xylotrophic fungi are widespread in all types of forests. The composition of their primary and secondary metabolites including biologically active compounds depends on species and growth substrate; therefore, fungi can become a valuable raw material for biotechnology, pharmaceuticals , and food industry. Fomitopsis pinicola is one of the common species in Russia and Europe, growing predominantly on Pinus sylvestris L., but in mixed forests of the Urals it is also found on Betula pendula Roth. As metabolism of angiosperms and gymnosperms, and their timber properties are different, growth substrate could affect the chemical composition of fungi fruit bodies; therefore our study aimed at metabolite composition of extracts, obtained from F. pinicola collected from birch and pine, and their antioxidant activity. Qualitative analysis revealed alkaloids, phenolics, and anthraquinones. Saponins were found only in the samples obtained from pine. Thin layer chromatography of extracts revealed the same qualitative composition of phenolics, but their amount was higher on birch-4.2 mg g-1 then on pine-3.1 mg•g-1. In ABTS test extracts showed the same antiradical activity. The metabolomics profile obtained by UHPLC-MS totally revealed 116 compounds, and each fungi sample contained more than 70 of them. Thus, the type of substrate influenced on the profile of metabolites and quantitative composition in F. pinicola fruit bodies.
... Previous studies in our laboratory have demonstrated the antioxidant and anti-inflammatory activities F. pinicola (Ravikumar et al., 2018). Despite numerous cell culture experiments have been carried out to demonstrate the anticancer properties of F. pinicola, reports on in vivo studies are limited (Bishop, 2020). In this study, we examined the antineoplastic activity of F. pinicola collected from the coniferous forests of Kashmir Himalayas. ...
... Fomitopsis piniola is reported to provide nutritional and therapeutic benefits and is used in Chinese and Korean folklore medicines as an antiinflammatory agent. (Cheng, Lin, Lur, Chen, & Lu, 2008, Bishop, 2020. Our previous study found that F.pinicola possessed profound antioxidant and anti-inflammatory activities (Ravikumar et al., 2018). ...
... However, further studies to evaluate the clinical potential of the bioactive component of this mushroom responsible for antineoplastic activity deserve adequate scientific inputs. F. pinicola has been used in Chinese and Korean folk medicines as an anti-inflammatory agent (Cheng et al., 2008) and the mushroom has shown non-toxic by anecdotal evidence over centuries (Bishop, 2020). However, the present study is the first report of the isolation and elucidation of 11-α-acetoxykhivorin as the anticancer bioactive component from F. pinicola. ...
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Fomitopsis pinicola (Sw.:Fr.) P. Karst is used in Chinese and Korean traditional medicine The study was aimed to evaluate the anticancer activity of bioactive extract of F. pinicola, mechanism of activity and to identify the bioactive molecules. Ethyl acetate extract (EAE) of F. pinicola was assayed for cytotoxicity, antitumor activity, inhibition of cancerous skin papilloma, antiangiogenesis, inhibition of cell cycle progression and induction of apoptosis. Results showed significant cytotoxicity (IC50 of 100 µg/mL), inhibited tumor growth at a dose of 500 mg/kg, angiogenesis and cell cycle progression at G1 phase. HPTLC analysis of EAE showed 13 peaks indicating the chemical profile. LC-MS analysis revealed 11-α- acetoxykhivorin (RT 9.966, C14H44O12, MW 644.7095) as the major active chemical component. The results concluded that EAE of F. pinicola possessed significant antineoplastic activity. The observed anticancer activity might be assigned to the major chemical components of the extract.
... Fomitopsis pinicola (Swartz.: Fr) Karst (FPK) is a wood-decay fungus and a common medicinal fungus widely distributed in the temperate Northern Hemisphere (16). Previous studies have reported that FPK extracts have multiple biological effects, such as anti-cancer (17), antibacteria (18), anti-oxidation (19), anti-hypoglycemic (20) and anti-inflammation effects (21). ...
... It has often been used to treat wind-cold dampness, joint pain, and hyperglycemia (16). In recent years, many molecular biology studies have shown that the FPK extract has many other biological effects (17,19,21). Among them, the antiinflammatory effect of the FPK extract has attracted widespread attention (21,24). ...
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Background: As an intestinal non-specific inflammatory lesion, ulcerative colitis (UC) affects the health of many individuals. This study examined the possible beneficial effects of the chloroform extract of Fomitopsis pinicola (Swartz.: Fr) Karst (FPKc) on UC. Methods: The mice were given free access to drink with 4% dextran sulfate sodium (DSS) for 1 week to establish acute UC model. Next, 35 mg of FPKc or sulfasalazine (SASP) was given to the mice via gavage for 3 weeks. The disease activity index (DAI) and colonic mucosa damage index (CMDI) scores were calculated. The colon tissues of the mice were collected to measure the length and perform hematoxylin and eosin staining. The thymus and spleen indexes were determined. Interleukin (IL)-6, IL-8, tumor necrosis factor-α, aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum were determined. Results: FPKc or SASP treatment alleviated hematochezia and weight loss, ameliorated DAI and CMDI scores, and improved the crypt structure and length of the colon tissues. Relative to the UC model group, the spleen index in the FPKc group was reduced, which was accompanied by decreases of the IL-6 and IL-8 levels in the serum. FPKc also lowered the AST and ALT levels in the serum of the UC mice. Conclusions: FPKc protected the mice from DSS-induced UC injury. It may be that FPKc activates immune regulation and downregulates the expression of pro-inflammatory cytokines.
... These fungi are also important for biotechnology due to the production of cellulose and lignin degrading enzymes, with great value to the textile industry for cleaning oil-contaminated tributaries, as well as being useful in the production of pesticides (Maciel et al. 2010, Lomascolo et al. 2011, Bekai et al. 2012. Some species of Hymenochaetales and Polyporales are used to generate products with medicinal properties such as antiviral, antiinflammatory substances and cancer treatment (Grienke et al. 2014, Dos Reis et al. 2015, Bishop 2020. E c o l o g i c a l i n f o r m a t i o n a b o u t Hymenochaetales and Polyporales is still scarce in tropical forests (e.g. ...
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Hymenochaetales and Polyporales are important macrofungi for the maintenance of tropical forests, since they act directly in the nutrient cycling of the wood decomposition. In the Amazon, the largest tropical forest in the world, knowledge about Agaricomycetes is still insipient, since many areas have not yet been inventoried and new records appear each new study. To increase ecological knowledge about the Hymenochaetales and Polyporales, in the Brazilian Amazon region, collections were conducted in western Pará, Brazil, relating these fungi to the substrate they colonize and to environmental variables. 91 species were identified, with greater macrofungi richness associated with the rainy season; these fungi showed preferences for dead woods, of small diameter (class 1 = 5,9 ˫ 39 cm) and, in stages of decomposition still rigid or intermediate. The abundance and richness of Hymenochaetales and Polyporales were influenced by air humidity and the assemblage composition was influenced by temperature, air humidity and rainfall. The results indicate a rich diversity for western Pará region, these species are associated with environmental conditions, and may be threatened by the increasing pressure of human activity in the Brazilian Amazon.
... Fomitopsis pinicola is a fungus that attacks wood a lot (Liu et al. 2021), it appears on trees annually (Han and Cui 2015) and belongs to the Kingdom of Fungi Division: Basidiomycota; Class: Agaricomycetes; Order: Polyporales; Family: Fomitopsidaceae; Genus: Fomitopsis; Species: F. pinicola (Bishop 2020). ...
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This article presents a literature review on the chemical composition, antimicrobial activities of cedar oils, and the main diseases this tree is subjected to. The studies included in this review have drawn upon several databases including Scopus, Springer, ScienceDirect, Web of sciences. The keywords used in data collection were C. atlantica M, C. libani L, C. deodara L, C. brevifolia H, Red ring rot (M’jej), Cubic brown rot (Saboune). Genus Cedrus is rich in bioactive molecules such as himachalenes, atlantones and generally terpenes. These molecules have an important medicinal and cosmetic properties maintained by the inhibition and destruction of many bacteria and fungi, along with other several biological activities. Cedar suffers from pests and fungal attacks, which cause two types of fungal decay: the first one is brown cubic rot caused by Fomitopsis pinicola or Ungulina officinalis, and the red ring rot caused by Trametes pini or Phellinus chrysoloma.
... (Fomitopsidaceae, Agaricomycetes) is a well-known medicinal mushroom that has been commonly used in Chinese traditional medicine and Korean folk medicine for many years, and it is believed to be a non-toxic medicinal mushroom that has many clinical effects on the human body with no sub-acute toxic impacts. 11 Numerous principal chemical constituents like steroids, triterpenoids, and heterogalactans exert beneficial medicinal effects such as anti-diabetic, anti-inflammatory, anti-tumor, anti-microbial, as well as powerful anti-oxidant activities. These principal compounds show important medicinal effects on the human body by providing a shield effect to the internal organs against diseases and by healing the damaged tissues and organs. ...
Considering the impact of oxidative stress on the development of many diseases, together with the role of natural antioxidants in maintaining physiological balance in humans, medicinal mushrooms are potential sources of bioactive compounds against many diseases. In the present work, in vitro evaluation of the biological activities of the alcoholic extracts of two wild tree mushrooms, namely, Ganoderma applanatum and Fomitopsis pinicola, has been performed. Extraction of G. applanatum (GAE) and F. pinicola (FPE) was conducted with 60% ethanol and 100% ethanol sequentially. UPLC-MS/MS identification was conducted on the two mushrooms extracts. A total of 15 substances were identified in GAE, including 3 spiro meroterpenoids and 12 triterpenoids; a total of 14 chemical constituents were iden¬tified in FPE, including 8 triterpenoids, 4 triterpene glycosides, 1 lanosterol, and 1 lanostanoid. The resulting extracts were examined for their in vitro antioxidative and cytoprotective effects against AAPH-induced oxidative damage. Our results demonstrated that both extracts have potent antioxidative activities, when GAE was 0.2 mg/mL, the clearance rates of DPPH and ABTS have reached 93.34% and 99.93%, respectively. When FPE was 1.4 mg/mL and 0.6 mg/mL, the scavenging rates of DPPH and ABTS have reached 91.76% and 100%, respectively. Both the alcoholic extracts of G. applanatum and F. pinicola were able to protect the AAPH-induced damage and could effectively inhibit cell aging via β-galactosidase (SA β-gal) staining activity test and scanning electron microscopy analysis.
... However, further studies are required to characterize the anticancer effect of F. pinicola. Such investigations would be interesting in order to ascertain the therapeutic benefits of this mushroom as an anticancer agent [34]. The added advantage is that F. pinicola has been reported nontoxic by anecdotal evidences and has been popular in folklore medicine. ...
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Mushrooms represent a major yet largely untapped source of therapeutically useful bioactive compounds. Despite mushrooms were in use since antiquity in traditional folk medicine attempts to isolate their bioactive components and to elucidate their medicinal properties have started only recently. Many pharmaceutical substances with unique properties were recently extracted from mushrooms and made their way all over the world. A number of medicinal mushrooms have been identified to possess anticancer effects recently. Some of the well-known examples are Lentinan from Lentinus edodes, Krestin from Trametes versicolor, Ganopoly from Ganoderma lucidum and Schizophyllan from Schizophyllum commune. We investigated the anticancer activities of a number of medicinal mushrooms in our laboratory. Some of the recent scientific evdences on the anticancer activities of Ganoderma lucidum, Phellinus rimosus, and Fomitopsis pinicola are discussed in this short review.
Background Fomitopsis officinalis (Vill. ex Fr. Bond. et Sing) is a medicinal mushroom, commonly called ‘Agarikon’, traditionally used to treat cough and asthma in the Mongolian population. Objective The objective of this study was to examine the significance of biological activity of F. officinalis, and evaluate the antioxidant and anticancer activity of six fractions of F. officinalis residues (Fo1-powder form dissolved in ethanol, Fo2-petroleum ether residue, Fo3-chloroformic, Fo4-ethylacetate, Fo5-buthanolic, and Fo6-water-ethanolic) against hepatocellular carcinoma cells. Methods We performed in vitro studies of cell proliferation and viability assay, annexin V-FITC/Propidium Iodide assay, and NF-kB signaling pathway by immunoblot analysis. Results Our findings revealed that all six fractions/extracts have antioxidant activity, and somehow, they exert anticancerous effects against cancer cells. In cancerous cell lines (HepG2 and LO2), Fo3 chloroformic extract promoted the cancer cell apoptosis, cell viability, activated G2/M-phase cell cycle, and selectively induced NF-kB proteins, revealing itself as a novel antitumor extract. Conclusion This study reports that Fo3-chloroformic extract is rich in antitumor activity; it was previously not investigated in cancer. To study the impact of F. officinalis among natural products to treat/prevent oxidative stress disorders or cancers, further examinations are needed. However, this study assessed only one extract, Fo3-chloroformic, which has a significant impact on cancer cell lines.
Twelve undescribed lanostane-type triterpenes, and twenty-two known triterpenes were isolated and identified from a medicinal bracket fungus Fomitopsis pinicola (Sw.) P. Karst. The structures of these compounds were determined by spectroscopic and spectrometric analyses. The antiinflammatory potential of thirty-two triterpene compounds was evaluated using neutrophils as an assay model, and pinicolasin J was the most potent inhibitor of superoxide anion generation and elastase release, with IC50 values of 1.81 ± 0.44 and 2.50 ± 0.64 μM, respectively. This study provides scientific insight into the nutritional supplement value and medicinal development of Fomitopsis pinicola.
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Two new species, Fomitopsis mounceae and F. schrenkii (Polyporales, Basidiomycota) in the F. pinicola species complex in North America, are described and illustrated. Previous molecular phylogenetic analyses identified three well-delimited lineages that represent F. mounceae and F. ochracea from Canada, the Appalachian Mountains, and the northern United States and F. schrenkii from western and southwestern regions of the United States. Fomitopsis pinicola sensu stricto is restricted to Eurasia and does not occur in North America. Morphological descriptions of basidiocarps and cultures for F. mounceae, F. schrenkii, and F. ochracea are presented. The three species are readily differentiated by nuc rDNA internal transcribed spacer (ITS1-5.8S-ITS2 = ITS) sequence, geographic distribution, and basidiospore size. Polyporus ponderosus H. Schrenk is an earlier illegitimate synonym of F. schrenkii. Both F. mounceae and F. schrenkii have a heterothallic multiallelic incompatibility system.
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Prediction of taxonomy for marker gene sequences such as 16S ribosomal RNA (rRNA) is a fundamental task in microbiology. Most experimentally observed sequences are diverged from reference sequences of authoritatively named organisms, creating a challenge for prediction methods. I assessed the accuracy of several algorithms using cross-validation by identity, a new benchmark strategy which explicitly models the variation in distances between query sequences and the closest entry in a reference database. When the accuracy of genus predictions was averaged over a representative range of identities with the reference database (100%, 99%, 97%, 95% and 90%), all tested methods had ≤50% accuracy on the currently-popular V4 region of 16S rRNA. Accuracy was found to fall rapidly with identity; for example, better methods were found to have V4 genus prediction accuracy of ∼100% at 100% identity but ∼50% at 97% identity. The relationship between identity and taxonomy was quantified as the probability that a rank is the lowest shared by a pair of sequences with a given pair-wise identity. With the V4 region, 95% identity was found to be a twilight zone where taxonomy is highly ambiguous because the probabilities that the lowest shared rank between pairs of sequences is genus, family, order or class are approximately equal.
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Background/aims: Non-toxic fomitopsis is has been traditionally used in folk medicine in many countries for its anti-inflammatory and anti-vascular disease activities. The present study investigates the antitumor effect of Fomitopsis pinicola (Sw. Ex Fr.) Karst chloroform extract (FPKc) on S180 tumor cells in vitro and in vivo and we determined the underlying mechanisms. Methods: HPLC was employed to analyze the constituents of FPKc. In-vitro 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to quantify the growth inhibition of FPKc; Propidium iodide (PI) exclusion assay and scanning electron microscopy (SEM) were used to observe the damage on the cell membrane and the changes of the cell morphology; Staining with Hoechst 33342/propidium iodide (HO/PI) and the application of the Annexin V-FITC/PI analysis permitted to observe the cell death triggered by FPKc; DNA damage and cell cycle arrest were detected by flow cytometry; Rhodamine 123 (RH123) and Cytochrome C were used as dyes to investigate the alterations of the mitochondria. In-vivo tumor inhibition and mice survival time were determined. Results: The results of the HPLC assay indicated that FPKc might contain DA (dehydroeburiconic acid), PA (pachymic acid), and ES (ergosterol), at percentages of 0.25%, 17.8%, and 10.5%, respectively. Concerning the study of the biological function, the results showed that FPKc exhibited preferential and significant suppression of proliferation on specific cell lines including S180, HL-60, U937, K562, SMMC-7721, and Eca-109 cells, which induced plasma membrane and cell morphology damages, triggering S180 tumor-cells late apoptosis and leading to DNA damage and S phase arrest. Mitochondria were suspected to play a vital role in these changes. In vivo data indicated that FPKc inhibited the solid tumor growth and prolonged the survival time of tumor-bearing mice. Moreover, FPKc provoked only little damage on normal cells in vitro and also on normal tissues in vivo. Conclusion: FPKc inhibited S180 tumor cells growth and prolonged the lifespan of mice. In vitro, we found that FPKc induced S180 tumor cells apoptosis and cell cycle arrest, possibly via the mitochondrial pathway.
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Fungal taxonomy and ecology have been revolutionized by the application of molecular methods and both have increasing connections to genomics and functional biology. However, data streams from traditional specimen- and culture-based systematics are not yet fully integrated with those from metagenomic and metatranscriptomic studies, which limits understanding of the taxonomic diversity and metabolic properties of fungal communities. This article reviews current resources, needs, and opportunities for sequence-based classification and identification (SBCI) in fungi as well as related efforts in prokaryotes. To realize the full potential of fungal SBCI it will be necessary to make advances in multiple areas. Improvements in sequencing methods, including long-read and single-cell technologies, will empower fungal molecular ecologists to look beyond ITS and current shotgun metagenomics approaches. Data quality and accessibility will be enhanced by attention to data and metadata standards and rigorous enforcement of policies for deposition of data and workflows. Taxonomic communities will need to develop best practices for molecular characterization in their focal clades, while also contributing to globally useful datasets including ITS. Changes to nomenclatural rules are needed to enable valid publication of sequence-based taxon descriptions. Finally, cultural shifts are necessary to promote adoption of SBCI and to accord professional credit to individuals who contribute to community resources.
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Fungal species with a broad distribution may exhibit considerable genetic variation over their geographic ranges. Variation may develop among populations based on geographic isolation, lack of migration, and genetic drift, though this genetic variation may not always be evident when examining phenotypic characters. Fomitopsis pinicola is an abundant saprotrophic fungus found on decaying logs throughout temperate regions of the Northern Hemisphere. Phylogenetic studies have addressed the relationship of F. pinicola to other wood-rotting fungi, but pan-continental variation within F. pinicola has not been addressed using molecular data. While forms found growing on hardwood and softwood hosts exhibit variation in habit and appearance, it is unknown if these forms are genetically distinct. In this study, we generated DNA sequences of the nuc rDNA internal transcribed spacers (ITS), the TEF1 gene encoding translation elongation factor 1-α, and the RPB2 gene encoding the second largest subunit of RNA polymerase II for collections across all major geographic regions where this fungus occurs, with a primary focus on North America. We used Bayesian and maximum likelihood analyses and evaluated the gene trees within the species tree using coalescent methods to elucidate evolutionarily independent lineages. We find that F. pinicola sensu lato encompasses four well-supported, congruent clades: a European clade, southwestern US clade, and two sympatric northern North American clades. Each clade represents distinct species according to phylogenetic and population-genetic species concepts. Morphological data currently available for F. pinicola do not delimit these species, and three of the species are not specific to either hardwood or softwood trees. Originally described from Europe, F. pinicola appears to be restricted to Eurasia. Based on DNA data obtained from an isotype, one well-defined and widespread clade found only in North America represents the recently described Fomitopsis ochracea. The remaining two North American clades represent previously undescribed species. © 2016 by The Mycological Society of America, Lawrence, KS 66044-8897.
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Ganoderma lucidum (lingzhi) has been used for the general promotion of health in Asia for many centuries. The common method of consumption is to boil lingzhi in water and then drink the liquid. In this study, we examined the potential anticancer activities of G. lucidum submerged in two commonly consumed forms of alcohol in East Asia: malt whiskey and rice wine. The anticancer effect of G. lucidum, using whiskey and rice wine-based extraction methods, has not been previously reported. The growth inhibition of G. lucidum whiskey and rice wine extracts on the prostate cancer cell lines, PC3 and DU145, was determined. Using Affymetrix gene expression assays, several biologically active pathways associated with the anticancer activities of G. lucidum extracts were identified. Using gene expression analysis (real-time polymerase chain reaction [RT-PCR]) and protein analysis (Western blotting), we confirmed the expression of key genes and their associated proteins that were initially identified with Affymetrix gene expression analysis.
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Polypores have been applied in traditional Chinese medicine up to the present day, and are becoming more and more popular worldwide. They show a wide range of bioactivities including anti-cancer, anti-inflammatory, antiviral and immuno-enhancing effects. Their secondary metabolites have been the focus of many studies, but the importance of fungal strain for bioactivity and metabolite production has not been investigated so far for these Basidiomycetes. Therefore, we screened several strains from three medicinal polypore species from traditional European medicine: Fomes fomentarius, Fomitopsis pinicola and Piptoporus betulinus. A total of 22 strains were compared concerning their growth rates, optimum growth temperatures, as well as antimicrobial and antifungal properties of ethanolic fruit body extracts. The morphological identification of strains was confirmed based on rDNA ITS phylogenetic analyses. Our results showed that species delimitation is critical due to the presence of several distinct lineages, e.g. within the Fomes fomentarius species complex. Fungal strains within one lineage showed distinct differences in optimum growth temperatures, in secondary metabolite production, and accordingly, in their bioactivities. In general, F. pinicola and P. betulinus extracts exerted distinct antibiotic activities against Bacillus subtilis and Staphylococcus aureus at minimum inhibitory concentrations (MIC) ranging from 31-125 μg mL−1; The antifungal activities of all three polypores against Aspergillus flavus, A. fumigatus, Absidia orchidis and Candida krusei were often strain-specific, ranging from 125-1000 μg mL−1. Our results highlight that a reliable species identification, followed by an extensive screening for a ‘best strain’ is an essential prerequisite for the proper identification of bioactive material.
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Background Fomitopsis pinicola (Sw. Ex Fr.m) Karst (FPK) which belongs to the Basidiomycota fungal class is one of the most popular medical fungi in China. It has been used for many diseases: cancer, heart diseases, diabetes and so on. However, little study on the pro-apoptotic effect and migration inhibition of FPK chloroform extract (FPKc) has been reported and the possible involved mechanism has not been illuminated. Methodology/Principal Findings Chemical analysis was performed by HPLC which showed ergosterol (ES) concentration was 105 µg/mg. MTT assay revealed that FPKc could selectively inhibit SW-480 cells viability with the IC50 of 190.28 µg/ml. Wound healing and transwell assay indicated that FPKc could inhibit the migration of SW-480 cells obviously, FPKc could also dramatically decreased the matrix metalloproteinases-2, 9 (MMP-2 and MMP-9) expression. Annexin V–FITC/PI staining, nuclear Hoechst 33342 staining and DNA fragmentation analysis revealed that FPKc and ES could induce SW-480 cells apoptosis. The apoptosis process closely involved in ROS accumulation and depletion of GSH, activation of caspase 3, poly (ADP-ribose) polymerase (PARP) degradation. FPKc could also up-regulate P53 expression and thus lead to G1 phase arrest. When SW-480 cells were pretreated with N-acetylcysteine (NAC), the ROS generation, cell viability and apoptotic ratio were partially declined, which indicated that ROS was vertical in the pro-apoptosis process induced by FPKc. Moreover, in the whole process, ES which has been previously found in FPKc had the similar effect to FPKc. Thus we could conclude that ES, as one of the highest abundant components in FPKc, might also be one of the active constituents. Conclusion/Significance FPKc could inhibit the migration of SW-480 cells, induce SW-480 cells G1 phase arrest and cause ROS-mediated apoptosis effect. And ES might be one of the effective constituents in the whole process.