Potential of Mushrooms Bioactive for the Treatment of Skin Diseases and Disorders

Abstract

Mushrooms have long been revered not only as a staple food source but also for their potential medicinal properties. Their role as a natural repository of bioactive compounds positions them uniquely in the pharmaceutical domain, with particular relevance to cosmeceuticals and nutricosmetics. The global ethnobotanical and ethnopharmacological chronicles highlight the traditional application of mushrooms against many diseases, with many even fnding their way into cosmetic formulations. This review aims to consolidate the existing knowledge regarding the efcaciousness of mushroom-derived bioactives in the realm of skin disorders and diseases. In addition, it sheds light on the instances where certain mushroom species have been implicated in causing dermatological reactions, underscoring the dual nature of these fungal entities. A comprehensive assessment was undertaken involving ethnobotanical databases and relevant scientifc literature to identify mushrooms used traditionally for treating skin conditions. In addition, contemporary research elucidating the biological activities of these mushrooms, specifcally their an-tioxidant, anti-infammatory, antimicrobial, and wound-healing capabilities, was scrutinized. Special attention was accorded to instances of contact dermatitis induced by mushrooms, notably the shiitake fungus. Preliminary fndings reinforce the therapeutic potential of certain mushrooms in managing skin ailments, attributed primarily to their antioxidant, anti-infammatory, and antimicrobial properties. Conversely, some species, prominently shiitake, emerged as potent dermatitis triggers. Mushrooms undeniably harbor an array of compounds that can be instrumental in treating various skin conditions, thereby underscoring their potential in dermatological applications. However, an understanding of their dual nature, acting both as a remedy and a trigger for certain skin reactions, is essential for their judicious application in skin care. Further research is mandated to unravel the comprehensive pharmacological spectrum of these fungal treasures.

Full text

Review Article
Potential of Mushrooms Bioactive for the Treatment of Skin
Diseases and Disorders
Nanjangud V. Anil Kumar ,
1
Cristina Quispe ,
2
Jes ´
us Herrera-Bravo ,
3
Lisandra Herrera Bel´
en,
3
P´
ıa Loren,
4
Luis A. Salazar ,
4
Victor Silva,
5
Ilkay Erdogan Orhan,
6
F. Sezer Senol Deniz,
6
Elifsu Nemli,
7
Esra Capanoglu,
7
Ahmed Olatunde ,
8
Nath´
alia Cristina Cirone Silva,
9
Jelena Zivkovic,
10
Eman M. Shorog,
11
Daniela Calina ,
12
and Javad Sharifi-Rad
13
1
Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, India
2
Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda Arturo Prat 2120, Iquique 1110939, Chile
3
Departamento de Ciencias B´asicas, Facultad de Ciencias, Universidad Santo Tomas, Santiago, Chile
4
Center of Molecular Biology and Pharmacogenetics, Scientic and Technological Bioresource Nucleus,
Universidad de La Frontera, Temuco 4811230, Chile
5
Departamento de Proceso Diagn´
ostico y Evaluaci´
on, Facultad de Ciencias de la Salud, Universidad Cat´
olica de Temuco,
Manuel Mont 056, Temuco, Chile
6
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara 06330, T¨urkiye
7
Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak,
Istanbul 34469, T¨
urkiye
8
Department of Medical Biochemistry, Abubakar Tafawa Balewa University, Bauchi 740272, Nigeria
9
Universidade de Campinas (UNICAMP), Campinas 13083-862, Sao Paulo, Brazil
10
Institute for Medicinal Plant Research “Dr Josif Panˇ
ci´
c”, Tadeuˇ
sa Koˇ
s´
cuˇ
ska 1, Belgrade 11000, Serbia
11
Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
12
Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova 200349, Romania
13
Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador
Correspondence should be addressed to Cristina Quispe; elquispe@unap.cl, Jes´us Herrera-Bravo; jesusherrerabr@santotomas.cl,
Daniela Calina; calinadaniela@gmail.com, and Javad Shari-Rad; javad.sharirad@gmail.com
Received 30 August 2023; Revised 6 November 2023; Accepted 25 November 2023; Published 12 December 2023
Academic Editor: Seyed Mohammad Taghi Gharibzahedi
Copyright ©2023 Nanjangud V. Anil Kumar et al. is is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Mushrooms have long been revered not only as a staple food source but also for their potential medicinal properties. eir role as
a natural repository of bioactive compounds positions them uniquely in the pharmaceutical domain, with particular relevance to
cosmeceuticals and nutricosmetics. e global ethnobotanical and ethnopharmacological chronicles highlight the traditional
application of mushrooms against many diseases, with many even nding their way into cosmetic formulations. is review aims
to consolidate the existing knowledge regarding the ecaciousness of mushroom-derived bioactives in the realm of skin disorders
and diseases. In addition, it sheds light on the instances where certain mushroom species have been implicated in causing
dermatological reactions, underscoring the dual nature of these fungal entities. A comprehensive assessment was undertaken
involving ethnobotanical databases and relevant scientic literature to identify mushrooms used traditionally for treating skin
conditions. In addition, contemporary research elucidating the biological activities of these mushrooms, specically their an-
tioxidant, anti-inammatory, antimicrobial, and wound-healing capabilities, was scrutinized. Special attention was accorded to
instances of contact dermatitis induced by mushrooms, notably the shiitake fungus. Preliminary ndings reinforce the therapeutic
potential of certain mushrooms in managing skin ailments, attributed primarily to their antioxidant, anti-inammatory, and
antimicrobial properties. Conversely, some species, prominently shiitake, emerged as potent dermatitis triggers. Mushrooms
Hindawi
Journal of Food Biochemistry
Volume 2023, Article ID 5915769, 26 pages
https://doi.org/10.1155/2023/5915769

undeniably harbor an array of compounds that can be instrumental in treating various skin conditions, thereby underscoring their
potential in dermatological applications. However, an understanding of their dual nature, acting both as a remedy and a trigger for
certain skin reactions, is essential for their judicious application in skin care. Further research is mandated to unravel the
comprehensive pharmacological spectrum of these fungal treasures.
1. Introduction
e skin is the outermost organ, covering and protecting the
body from the external environment Reference [1] and its
structure has three layers: epidermis, dermis, and sub-
cutaneous fat tissues [2]. Among the several functions of the
skin, layers are protected from the external environment,
internal homeostasis maintenance, protection from ultra-
violet light damage, and defense after microorganism entry
(Figure 1). Skin diseases are shared worldwide, constituting
over 30% of general disorders [3]. Skin diseases and dis-
orders (SDDs) vary greatly in symptoms and severity. ey
can be temporary or permanent and may be painless or
painful. erefore, a considerable amount of research has
focused on bioresources to develop novel drugs for skin
diseases, where mushrooms are present as a source of
valuable compounds. Mushrooms are regarded worldwide
as a component of gourmet cuisine and valued by hu-
mankind as a culinary wonder for their unique avor. Al-
though more than 2,000 species of mushrooms exist in
nature, merely 25 are widely accepted as food, and few are
commercially cultivated (Supplementary File 1). In addition,
mushrooms comprise a vast yet largely untapped source of
powerful new potential pharmaceutical substances. Poly-
saccharides, notably beta-glucans, activate Langerhans cells
and macrophages, modulating immune responses and in-
ammatory processes in skin conditions [4]. Triterpenoids
play a key role in skin health by inhibiting the synthesis of
proinammatory cytokines such as TNF-alpha and IL-6 and
suppressing COX-2 expression, which is pivotal in the in-
ammation cascade [5]. Similarly, phenolic compounds
bolster skin’s defenses by upregulating endogenous anti-
oxidant enzymes while also inhibiting oxidative enzymes
like xanthine oxidase, mitigating the eects of oxidative
stress [4]. Lectins contribute to cancer management by
inducing apoptosis in malignant cells through both intrinsic
and extrinsic pathways and curbing angiogenesis, which is
vital in halting the progression of melanoma and other skin
tumors [6]. Furthermore, ergothioneine, a compound that
accumulates in mitochondria, provides a shield against
mitochondrial DNA damage, maintaining cellular integrity
and skin function [7]. e active form of Vitamin D, cal-
citriol, has a profound inuence on skin health, modulating
keratinocyte growth and dierentiation, which are key in
conditions like psoriasis [8]. Kojic acid, a well-known
inhibitor of the melanin-producing enzyme tyrosinase,
alters melanogenesis, oering a lightening eect on hy-
perpigmented areas [9]. e essential trace element se-
lenium is integral in protecting against UV-induced
cellular damage and inhibiting apoptosis of keratinocytes,
due in part to its incorporation into antioxidant
selenoproteins [10]. Omega-3 fatty acids, present in some
mushrooms, are potent antiinammatory agents capable
of inhibiting the NF-kB pathway, thereby reducing in-
ammatory mediators in skin diseases such as atopic
dermatitis [11, 12]. Lastly, chitin and chitosan, compo-
nents of mushroom cell walls, are shown to enhance -
broblast proliferation and collagen synthesis, speeding up
wound healing and fortifying the skin barrier, under-
scoring the extensive therapeutic potential of mushrooms
in dermatological applications [13]. On this basis, mul-
tiple biological activities have been documented related to
skin disease. Mushrooms like Trametes versicolor (Turkey
Tail) contain polysaccharides, which are believed to have
immunomodulatory eects; these can potentially help in
conditions like psoriasis, where the immune response is
misdirected towards skin cells [14]. Ganoderma lucidum
contains triterpenoids, which might have anti-
inammatory and antihistamine properties, benecial
for skin conditions exacerbated by inammation and
allergic reactions [15]. e antioxidant activity of poly-
saccharides from several species such as Pleurotus spp.
and Agaricus spp. [16–18], the potential of mushroom
extract to decrease the secretion of proinammatory
mediators [19, 20], the antimicrobial activity of phyto-
chemicals coming from mushroom extracts against bac-
teria and fungi activity [21], and the wound healing of
mushroom species as adjuvants in new forms of treatment
of skin damage, in dierent diseases, such as diabetes
[22, 23], have been documented. However, some mush-
rooms also cause dermatitis, and one of the most common
is that generated by the shiitake fungus, this being the best
known and used. us, this review aimed to investigate
the ethnobotanical data regarding the use of mushrooms
for the potential treatment of SDDs, the biological activity
in both in vivo and in vitro studies, and some contact
dermatitis caused by mushrooms.
2. Methodology
e primary objective of this comprehensive review was to
collate and assess the ethnobotanical evidence surrounding
the utilization of mushrooms in the treatment of skin dis-
eases and disorders (SDDs), to explore their biological ac-
tivity in in vivo and in vitro studies, and to catalog any
reported cases of contact dermatitis associated with
mushroom exposure. To achieve a comprehensive literature
search, multiple databases were scoured, including ethno-
botanical databases, PubMed/MEDLINE, ScienceDirect,
Web of Science, Google Scholar, Embase, and the Cochrane
Library; a combination of keywords and MeSH (Medical
Subject Headings) terms were employed to maximize search
2Journal of Food Biochemistry

precision: “Mushrooms,” “Ethnobotany,” “Skin diseases,”
“Dermatology,” “Fungal extracts,” “Contact dermatitis,”
“In vivo,” “In vitro.” Boolean operators (AND, OR) were
used to further rene the search, e.g., “Mushrooms” AND
“Ethnobotany” OR “Bioactive compounds” AND
“Dermatology.”
2.1. Inclusion Criteria. Ethnobotanical records specifying
the use of mushrooms for SDDs; studies focusing on the
biological ecacy of mushroom extracts or compounds in
both in vivo and in vitro setups; reports of contact dermatitis
due to mushroom exposure; experimental, clinical trials,
observational studies, and case studies; full-text articles
available in English; articles published within the last
10 years.
2.2. Exclusion Criteria. Articles not directly related to the
therapeutic or adverse eects of mushrooms on skin con-
ditions; studies lacking direct ethnobotanical relevance or
those not emphasizing in vivo or in vitro activity; articles
unavailable in full text or not in English; non-peer-reviewed
publications, such as literature reviews, opinion pieces, and
editorials; studies deemed to have insucient data or am-
biguous methodologies.
For each article that met the inclusion criteria, a struc-
tured data extraction form was used to capture: authors, year
of publication, article title, and source; traditional uses,
regions, and cultural practices linked with mushroom use;
design, mushroom type under study, targeted skin
condition, main ndings, and conclusions drawn; specic
compounds identied, their quantities, and their roles
(therapeutic or harmful); occurrences, symptomatic pre-
sentations, the mushroom species responsible, and resulting
outcomes. e most representative data were methodically
organized, summarized, and reported to present a holistic
understanding of the current knowledge on the topic.
3. Ethnobotanical Data regarding the Use of
Mushrooms in the Treatment of SDDs
Skin diseases constitute over 30% of general disorders [3]
worldwide. A large amount of research has focused on
bioresources to develop novel drugs for skin diseases, where
mushrooms are a source of valuable compounds. On the
other hand, the ethnobotanical and ethnopharmacological
use of mushrooms against various skin diseases has been
documented in dierent countries, and a number of species
have been used as cosmetic ingredients [24] (Table 1).
Mushroom species Ganoderma lucidum (Reishi) have been
a part of traditional Chinese medicine formulations to treat
various skin conditions, including rashes, wounds, and even
more severe conditions like eczema and psoriasis; also, the
native American tribes have been known to use certain
mushrooms in poultices to treat skin infections and minor
burns [41, 42]. Traditionally used in Siberian folk medicine,
Chaga has been applied topically to treat various skin
conditions [37, 43]; recent studies suggest that its high
content of antioxidants might play a role in reducing skin
inammation and improving overall skin health [41]. Apart
Figure 1: e structures of the skin. e epidermis, the outermost layer of the skin, is mainly composed of keratinocytes which undergo
a process of maturation and eventually form a protective layer. e epidermis contains four to ve sublayers, including the stratum basale,
stratum spinosum, stratum granulosum, stratum lucidum (only in thick skin like palms and soles), and stratum corneum. Dermis, situated
below the epidermis, the dermis consists of two sublayers: the papillary dermis and reticular dermis; it provides strength and elasticity to the
skin due to the presence of collagen and elastin bers. Hypodermis (subcutaneous layer) is the deepest layer of the skin, primarily made up of
adipose tissue (fat cells). Accessory structures include hair follicles, sweat and sebaceous glands, and nails. Hair follicles give rise to hair
which oers protection and plays a role in sensory functions. Sweat glands help in thermoregulation through perspiration, while sebaceous
glands produce sebum, an oily secretion that moisturizes the skin and hair.
Journal of Food Biochemistry 3

Table 1: Ethnopharmacological use of mushroom species relevant to SDDs.
Mushroom species Country used Ethnobotanical use References
Agaricus arvensis Schae. India For treating scalds and burns [25]
Agaricus campestris L.: Fr. Pakistan
Against wounds
[26]Against wounds and as a skin tonic
Agrocybe dura (Bolton) Singer Used as a skin tonic
Antrodia camphorata (M. Zang and C.H. Su) Sheng H. Wu,
Ryvarden, and T.T. Chang (formerly known as Taiwanofungus
camphoratus (M. Zang and C.H. Su) Sheng H. Wu, Z.H. Yu, Y.C.
Dai, and C.H. Su) (syn. Antrodia cinnamomea T.T. Chang and
W.N. Chou)
Taiwan Against itchy skin [27]
China Against itchy skin [28]
Astraeus hygrometricus (Pers.) Morgan
Pakistan Against wounds [26]
India Its spores against skin burns as ointment prepared with mustard
seed oil [25]
Auricularia auricula-judae (Bull.) Qu´
el. (syn. Hirneola
auricula-judae (Bull.) Berk.) Europe Astringent [29]
Bovista sp. Pers.
India
Its spores for treating bruised skin infections [25]
Bovista nigrescens Pers. Against broken skin or wounds [30]
Bovista plumbea Pers. Against skin infections [25]
Calvatia cyathiformis (Bosc) Morgan India Against wounds by powdering fruitbodies [25]
Mexico Against burns in dried and minced form [31]
Calvatia gigantea (Batsch) Lloy (syn. Langermannia gigantea
(Batsch) Rostk.)
Italy Against burns [32]
Europe For dressing wounds [29]
Calvatia utriformis (Bull.: Pers.) Jaap Italy Against burns [32]
Chlorophyllum brunneum (Farl. and Burt) Vellinga Pakistan Against wounds [26]
Clavulina rugosa (Fr.) Schroet. India Against skin diseases [30]
Coprinellus disseminatus (Pers.) J.E. Lange Pakistan Used as a skin tonic [26]
Coprinus comatus (O.F.Mull.: Fr.) Pers. India Against wounds, skin infections, and bruises [25]
Coprinus micaceus (Bull.: Fr.) Fr. For curing skin infections [25]
Cordyceps sinensis (Berk.) Sacc. China For curing night sweating [33]
4Journal of Food Biochemistry

Table 1: Continued.
Mushroom species Country used Ethnobotanical use References
Coriolopsis polyzona (Pers.) Ryvarden Tanzania
Against skin diseases
[34]
Daedaleopsis confragosa (Bolton) J. India [30]
Daldinia concentrica (Bolton) Ces. and De Not
Nigeria [35]
India Against itching and healing minor skin infections, applied by
mixing with coconut oil
[25]Entoloma bloxami (Berk. and Broome) Sacc
India
For curing skin diseases
Flammulina velutipes (Curt.) Singer Against skin diseases by mixing its ashes with vegetable oil
Fomes fomentarius (L.) Fr. (syn. Agaricus fomentarius (L.) Lam.,
Polyporus fomentarius (L.: Fr.) Fr.)
Against wounds
Korea Against alopecia [36]
Europe For wound cauterization
[29]
Fomitopsis betulina (Bull.) B.K. Cui, M.L. Han and Y.C. Dai (syn.
Piptoporus betulinus (Bull.) P. Karst., or Polyporus betulina (Bull.)
Fr.)
Russia, Poland, and other Baltic
countries Against wound bleeding
Fomitopsis ocinalis (Vill.) Bondartsev., Singer., (syn. Laricifomes
ocinalis (Vill.) Kotl., and Pouzar, syn. Fomes ocinalis (Vill.)
Bres.)
Ancient Greeks For inhibiting sweat secretion
Ganoderma applanatum (Pers.) Pat.
Tanzania
For cleaning wounds
[34]
Ganoderma boninense Pat. Against skin diseases and wounds
Ganoderma lucidum (Curtis) P. Karst. For cleaning wounds
Ganoderma tsugae Murrill
Geastrum mbriatum Fr. Mexico For softening baby’s skin [31]
Geastrum saccatum Fr.
Geastrum sessile Fr. Pakistan Used as a skin tonic [26]
Geastrum triplex Jungh.
India Its spores for curing skin diseases [25]
Pakistan Against wounds [26]
Mexico For softening baby’s skin [31]
Gomphus occosus (Schwn.) Singer India For eczema and athlete’s foot disease [25]
Hericium erinaceus (Bull.) Persoon China, Japan Against wounds [29]
Humaria hemisphaerica (Wigg.) Fuckel
India
For treating blisters on the skin [25]
Hygrocybe sp. (Schae.) P. Against skin diseases [30]
Hypsizygus tessellates (Bull.) Singer [25]
Inonotus hispidus (Bull.) P. Karst. As a topical disinfectant and for curing boils
Inonotus obliquus (Fr.) Pil´
at. (syn. Fuscoporia obliqua (Fr.)
Aoshima)
Russia, Poland, and other Baltic
countries As a topical disinfectant used as soap [29]
Ancient Greeks For washing wounds [37]
Langermannia gigantea (Batsch.: Fr.) Rostk. Pakistan Against wounds [26]
Mexico Against burns [31]Lycoperdon candidum Pers.
Lycoperdon echinatum Pers. India Against wounds [30]
Journal of Food Biochemistry 5

Table 1: Continued.
Mushroom species Country used Ethnobotanical use References
Lycoperdon perlatum Pers Mexico Against burns [31]
India Its spores against wounds and for curing skin [25]
Lycoperdon pyriforme Schae. Its spores against wounds
Mexico Against burns [31]
Macrolepiota procera (Scoop.) Singer Tanzania Against wounds [38]
Melanoleuca grammopodia Bull.
India
Against skin diseases [30]
Morchella vulgaris (Pers.) Boud. Against wounds [25]
Mycena galericulata (Scop.) Gray. Against skin diseases [30]
Peziza repanda Pers. For curing eczema [25]
Phallus sp. Junius ex Linnaeus Against wounds, skin infections, boils, or lesions
Phallus impudicus L. China As a balm [29]
India Against wounds [25]
Phellinus rimosus (Berk.) Pil´
at
Tanzania For cleaning wounds [34]
Cambodia Against wounds by chewing and spitting the whole fruitbody on
wounds [39]
Pholiota nameka (T.Itˆo) S.Ito and S.Imai Pakistan Against wounds [26]
Piptoporus betulinus (Bosc) Fr.
Pisolithus arhizus (Scop.) Rauschert India
Its spores against wounds and for curing skin to relieve burning,
itching, and minor healing infections [25]
Against skin diseases and wounds [30]
Pleurotus sp. (Fr.) P. Kumm. India For curing eczema in paste form by mixing its powdered fruitbody
with water [25]
Pleurotus dryinus (Pers.) P. Kumm. Pakistan Against wounds [26]
Pleurotus ostreatus (Jacq.: Fr.) P. Kumm. India Its spores against wounds [25]
Pleurotus sapidus Schulzer and Kalchbr. Against skin diseases and wounds [30]
Pleurotus tuber-regium (Rumph. ex Fr.) Singer Tanzania Against skin diseases [34]
Podaxis pistillaris (L.) Fr. India Against skin diseases and burns [25]
Pakistan Against wounds [26]
Polyporus sp. P.Micheli ex Adans. Tanzania Against skin diseases [34]
Ramaria stricta (Pers.) Qu´
el. India To enhance skin color in powdered form [25]
Russula delica (Pers.) Fr. India Against skin diseases and wounds [30]
Scleroderma sp. Pers. India Against wounds [25]
Pakistan Used as a skin tonic [26]
Scleroderma citrinum Pers. India Against skin diseases and wounds [30]
Scleroderma bovista Fr. Turkey Against skin wounds [40]
Sparassis spathulata (Schwein.) Fr. India Against skin diseases, e.g., rashes, itching, dryness, and healing of
wounds through mixing with butter or oil [25]
Termitomyces heimii Natarajan India
Wounds healing
[30]
Termitomyces marcocarpus Z.F. Zhang and X.Y. Ruan Pakistan [26]
Termitomyces microcarpus (Berk. and Broome) R. India [30]
6Journal of Food Biochemistry

Table 1: Continued.
Mushroom species Country used Ethnobotanical use References
Trametes versicolor (L.) Lloyd. H India Against dermatitis [25]
Ustilago maydis (DC.) Corda
Mexico
For softening baby’s skin
[31]Vascellum pratense (Pers.: Qu´
el.) Kreisel. Against burns
Vascellum qudenii (Bottomley) P. Ponce de Le´
on
Volvariella bombycina (Schae.) Singer Pakistan Against wounds [26]
Xylaria sp. Hill ex Schrank India For curing eczema [25]
Journal of Food Biochemistry 7

from its culinary uses, shiitake (Lentinula edodes) has been
employed in traditional East Asian practices for its skin-
healing properties; it was believed to rejuvenate the skin and
reduce signs of aging [44]. Looking over the ethnobotanical/
ethnopharmacological data related to mushrooms may keep
light on the medical/pharmaceutical research relevant to
skin diseases. For this purpose, our survey through literature
using PubMed/MEDLINE and Scopus databases indicated
the use of a limited number of mushroom species in eth-
nobotany/ethnopharmacology against skin-related diseases.
Given the increasing interest in natural and botanical
ingredients in skincare, many modern cosmetic and ther-
apeutic formulations now integrate mushroom extracts for
their potential benets; for instance, Reishi and Cordyceps
extracts are commonly found in creams and serums aiming
to provide antiaging and skin rejuvenating benets [45].
While traditional evidence supports the benets of mush-
rooms for skin health, rigorous clinical trials and scientic
validations are essential; the precise mechanisms, safety
proles, and dosage regimens need to be established.
Mushrooms, with their rich ethnobotanical history and
a plethora of bioactive compounds, present promising po-
tential for the treatment of various skin diseases; bridging
the gap between traditional practices and modern medicine
requires a comprehensive understanding and validation of
their pharmacological actions.
4. Mushrooms-Derived Biological Effects:
Therapeutic Potential for Managing SDDs
4.1. Antioxidant and Anti-Inammatory Activity.
Oxidative stress plays a pivotal role in the pathophysiology
of skin inammation, acting as both a trigger and a con-
sequence of inammatory processes. Various studies rec-
ognize mushrooms ‘therapeutic activity and nutritional
value [46–48]. ese fungi have shown antioxidant activity
highlighting polysaccharides as their primary metabolites
[49, 50], which is essential in several species such as
Pleurotus spp. and Agaricus spp. [16, 17]. In addition,
studies indicate that polysaccharides, phenols, avonoids,
fatty acids, and tocopherols, among other compounds, are
responsible for antioxidant activity [51]. For example,
phenolic compounds might stimulate the endogenous
production of antioxidant molecules in cells [52], inhib-
iting free radicals, sequestering oxygen, decomposing
peroxide, and chelating metal ion [53]. A comprehensive
review carried out by Sanchez [54] found that the active
components in mycelia extracts, sporocarps, and cultures
of these structures were responsible for the antioxidant
eect. e rst report on the antioxidant activity of aqueous
and methanolic extracts of Pleurotus ostreatus in distinct
growth stages was conducted by Gonz´
alez-Palma et al. [55].
In the study, avonoids and undetermined metabolites
were responsible for antioxidant activity, showing greater
reduction power in the case of aqueous extracts. In addi-
tion, Boonsong et al. [56] studied the antioxidant activity of
the edible mushroom species Lentinus edodes,Volvariella
volvacea,Pleurotus eous,Pleurotus sajor-caju, and
Auricularia auricular from extracts rich in phenols and
avonoids. L. edodes ethanolic extract showed the highest
antioxidant, chelating, and superoxide radical scavenging
activity, positively correlated with total avonoid and
phenol content [56]. In an investigation carried out by
Gebreyohannes et al. [57], the antioxidant potential of the
Auricularia spp. and Termitomyces spp. was evaluated using
the DPPH free radical method and expressed by the in-
hibitory concentration value (IC
50
). Extracts of both species
revealed suitable antioxidant activities in the range of IC
50
40–70 g/mL. e antioxidant capacity extracts from four
species of wild edible mushrooms (Pleurotus cystidiosus,
P. abellatus.,P. orida, and P. ostreatus) were evaluated in
a study conducted by Vishwakarma [58]. All species
exhibited signicant antioxidant properties; however,
P. ostreatus showed the highest antioxidant activity using
the DPPH, β-carotene and H
2
O
2
elimination assays. Chen
et al. [59] evaluated the antioxidant activity of melanin,
extracted from Auricularia auricula-judae in terms of its
capacity to eliminate free radicals and its antioxidant eects
in C. elegans. It was observed that at a concentration of
1 mg/mL, the free radical scavenging capacity exceeded
85%, inuencing the half-life and locomotion of C. elegans
[59]. On the basis of the fact that the production of reactive
oxygen species signicantly impacts the destruction of
collagen in the skin, Choi et al. studied the antioxidant
activity of Auricularia auricula-judae (Bull.) and its re-
lationship with collagen production in human keratino-
cytes. e extract obtained from this mushroom species
showed a positive eect in eliminating DPPH free radicals
and superoxide anions, with potential use in the skincare
industry [60]. An in vivo study by Son et al. revealed the
antiinammatory eect of mushroom extracts on ear
thickness, ear epidermal thickness, and eosinophil in-
ltration in the skin tissues of mice. eir antiinammatory
eect improved more signicantly with the aqueous frac-
tions produced by solid fermentation of Ganoderma luci-
dum on Artemisia capillaris leaves than with aqueous
samples of Artemisia capillaris leaves or Ganoderma luci-
dum [61]. According to another study by Ramya et al. [62]
focusing on the preventive eect on inammation of the
bioactive extract of the mushroom Morchella elata, skin
thickness, level of lipid peroxidation, and histopathological
alterations of mice were reduced, indicating the antiin-
ammatory eect of Morchella elata extracts [62].
4.2. Antimicrobial and Antifungal Activity. Mushrooms
contain bioactive compounds with potent antimicrobial and
antifungal properties in an era where Staphylococcus aureus
colonization and antimicrobial resistance are on the rise.
ese natural agents could be particularly benecial in
combating severe infections, such as fusariosis in immu-
nocompromised patients, providing alternative therapeutic
strategies in the context of hospital-acquired infections and
the challenge of invasive diseases following procedures like
allogeneic transplants [63]. Mushrooms need antibacterial
components to survive in their natural environment; they
have phytochemicals with antimicrobial action, positioning
them as potential pharmacological resources to control
8Journal of Food Biochemistry

resistant pathogens eectively. A study evaluated 35 wild
mushrooms from Kenyan forests. Trametes spp. (Arabuko-
Sokoke forest), Trametes spp., and Microporus spp. (Kaka-
mega forest) exhibited antimicrobial activities against a wide
variety of bacterial strains [57]. Another in vitro study
evaluated the extract from ve edible mushrooms against
Gram-positive bacteria (Bacillus cereus and Staphylococcus
aureus) and Gram-negative bacteria (Salmonella enteritidis
and Escherichia coli). Of the ve mushroom species,
A. brasiliensis presented the highest responses for antioxidant
and antibacterial activity [64]. ere is growing evidence of
the antimicrobial eect of volatile compounds produced by
P. spadiceum against plant fungi and bacteria [65]. In fruit
growing, the activity of the hydroalcoholic extract obtained
from the mushroom Lactarius deliciosus against Monilinia
fructicola, a pathogenic fungus that infects stone fruits such as
peach, nectarine, and plum in Brazil, was evaluated [66]. e
antimicrobial activity of mushroom extracts and the pro-
duction of phytochemicals known for their action against
bacteria and fungi depend on genetic factors, culture con-
ditions, pH, and the substrate composition inuencing the
metabolic pathway that allows the production of these
phytochemicals of biological interest [21]. Worldwide, more
studies are needed to clarify the role of these microbial
communities in both human health and pathology [67].
Table 2 shows examples of mushroom species with
antimicrobial and antifungal activity in SDDs.
5. Healing Activity
e wound healing process consists of four main phases:
homeostasis, inammation, proliferation, and remodeling
[76, 77]. Fibroblasts play a fundamental role in the process by
participating in the extracellular matrix generation. Several
investigations describe the wound healing role of mushrooms,
as potential adjuvants in skin damage treatment for dierent
diseases, such as diabetes [22]. Polysaccharides found
abundantly in various mushroom species play a crucial role in
enhancing skin hydration, improving its barrier function;
they also possess antiinammatory properties, aiding in re-
ducing skin redness and irritation [78]. Exhibiting antiin-
ammatory and antioxidant properties, triterpenoids derived
from mushrooms like Ganoderma lucidum (Reishi) help
soothe skin irritations and protect against oxidative damage.
Phenolic compounds present in mushrooms such as Agaricus
bisporus also act as powerful antioxidants, combating free
radicals that accelerate skin aging [78]. Commonly found in
mushrooms, ergosterol, when exposed to UV light, converts
to provitamin D2, which is benecial for skin health [78]; the
presence of essential amino acids and antioxidants in
mushrooms accelerates the wound healing process by pro-
moting collagen synthesis and reducing oxidative stress at the
wound site [78]. A review by Jones et al. [13] summarized the
role of chitin, chitosan, and other polysaccharides in the cell
walls of wound healing by mushrooms (Figure 2). ese
polysaccharides can accelerate proliferation in cells (such as
broblasts and keratinocytes), acting as a support matrix for
cell expansion and regeneration of damaged tissue [13]. A
study conducted by Wen et al. [79] revealed that the
polysaccharides extracted from Tremella fuciformis increased
collagen production, thus contributing to the wound healing
process [79]. Ganoderma lucidum is a mushroom species
studied for the healing activity of its extracts, rich in poly-
phenols and avonoids [80], as for its interaction with the skin
microbiota and its relationship with the inammatory pro-
cesses associated with wound healing [81]. In addition,
G. lucidum, studied by Abate et al. [82], showed the ethanolic
potential of its extract, rich in ganoderic acid, in increasing
cell migration patterns and accelerating the healing process,
mainly re-epithelialization [82]. One study showed that
Auricularia auricula-judae extract promoted the pro-
liferation, migration, and invasion of broblasts and kerati-
nocytes, as well as increasing the wound-healing process by
raising collagen synthesis and decreasing E-cadherin ex-
pression [83]. In the same way, Metacordyceps neogunnii
extract, another type of edible mushroom, slightly improved
the broblast cells (BJ-1) migration after 24 hours of exposure
to the extract [84]. Another study evaluated silver nano-
particles using extracts from Boletus edulis and Coriolus
versicolor showing improvements in the migration of murine
L929 broblast cells at low extract concentrations [75]. Re-
search conducted on extracts of immature bamboo mush-
rooms (Dictyophora indusiate) improved the healing process
by reducing metalloproteinase 2 (MMP-2) in broblasts.
ese mushrooms are highlighted as essential natural in-
gredients for skin-healing pharmaceutical products [85]. A
study that evaluated the eect of ethanolic extracts from 4
mushroom species (Pisolithus tinctorius,Russula capensis,
Imleria badia, and Pleurotus ostreatus) on in vitro models
(characteristic of the diabetic state), showed positive eects on
wound healing [86]. Mapoung et al. [83] investigated the
nutrient-rich macrofungi Auricularia auricula-judae in terms
of its wound-healing eects from the high amount of water-
soluble polysaccharide-rich extracts (AAP). e BALB/c
mice, six to eight weeks old males, were employed to observe
the wound closure in their skin by examination of three
groups, in which the wounds were sterilized with 0.9% of
normal saline, 1.0% w/v of AAP, and 2.5% w/v of AAP. e
results revealed that the group receiving 2.5% w/v of AAP
showed an observable wound contraction on day 9. In ad-
dition, the 2.5 and 1 w/v of AAP showed a strong wound
contraction on day 12, thus supporting the signicant po-
tential for accelerating the wound healing of polysaccharides
obtained from Auricularia auricula-judae [83]. In another in
vivo study by Krupodorova et al. [87]; the wound healing
activity of the aqueous extracts obtained from mushrooms
Ganoderma lucidum 1900 (Curtis) P. Karst and Crinipellis
schevczenkovi 31 Buchalo was investigated. e three months
old white albino male mice line FVB/Cg, were separated into
three groups, and treated with 20 LG. lucidum mycelium
extract and 20 LC. schevczenkovi mycelium extract for six
days, and the control group was treated with sterile distilled
water. e results demonstrated that the wound healing
process was more active on day 3 in mice treated with
aC. schevczenkovi extract than the treated group with
aG. lucidum extract. In contrast, the healing process was
similar on day 5 for both groups treated with mushroom
extracts. erefore, the wound-healing process in both groups
Journal of Food Biochemistry 9

Table 2: Overview of mushroom-derived compounds with antimicrobial and antifungal properties for skin disease management.
Mushroom
source and activity
Extract
and active molecules Pathogens targeted Mechanism/Benecial role in
SDDs Reference
Pleurotus ostreatus (Antimicrobial)Methanol and aqueous (Tannins, terpenoids,
alkaloids, avonoids, saponins, glycosides, steroids)
Shigella sp., Staphylococcus sp., Vibrio
sp., E. coli,Penicillium sp., Yeast and
Moulds
Disrupts pathogen cell walls, prevents
skin infections, and supports wound
healing
[68]
Pleurotus ostreatus (Antimicrobial) Water and ethanol E. coli,B. cereus,P. aeruginosa,
B. subtilis,S. typhi,S. aureus
Enhances skin integrity by preventing
pathogenic bacterial infections [21]
Trametes spp. (Arabuko-Sokoke
forest), Trametes,Microporus spp.
(Kakamega forest)Antimicrobial)
Chloroform, 70% ethanol, and hot water S. aureus,MRSA,K. pneumoniae,
P. aeruginosa,E. coli (clinical isolate)
Inhibits bacterial biolm formation,
useful in treating resistant skin
infections
[69]
Agaricus bisporus, et al.
(Antimicrobial)Ethanol (Gallic acid) B. cereus, S. aureus,E. coli,
S. enteritidis
Reduces inammation and microbial
growth on the skin [64]
Porostereum spadiceum (Antibacterial,
Antifungal)N-hexane (4-dichloro-4-methoxybenzaldehyde) C. michiganensis,R. solanacearum,
A. brassicicola,C. orbiculare
May be used for topical treatment
against skin-aecting plant pathogens [65]
Lentinus arcularius (Antibacterial,
Antifungal)Ethyl acetate E. coli,P. aeruginosa,S. aureus/C.
albicans,S. cerevisiae,A. niger
Protects against both bacterial and
fungal skin infections [70]
Lactarius deliciosus (Antifungal) Hydroalcoholic extract M. fructicola
Potential application in antifungal
treatments for skin aected by fruit
pathogen infections
[66]
Omphalotus japonicus (Antibacterial) Methanol (Omphalotols A and B) H. pylori
Possible applications in treating
H. pylori-associated dermatological
conditions
[71]
Cordyceps sinesis, et al. (Antibacterial) Ethanol K. pneumoniae,E. aerogenes,S. aureus
sub sp., B. thuringiensis
Can aid in the management of bacterial
infections of the skin [72]
Lentinula edodes (Antibacterial) Water and methanol S. aureus,K. pneumonia Could be useful in the topical treatment
of bacterial skin infections [73]
Sarcodon squamosus (Antibacterial,
Antifungal)Methanol
M. luteus,S. aureus,B. subtilis,
P. vulgaris,E. coli,Y. enterocolitica/C.
albicans
May oer a dual-action approach to
treating skin infections caused by
bacteria and fungi
[74]
Coriolus versicolor Boletus edulis
(Antibacterial,Antifungal)Distilled water
P. aeruginosa,K. pneumonia,
S. aureus,E. faecalis/C. albicans,
C. utilis
Supports the treatment of infections and
enhances skin microbiota balance [75]
10 Journal of Food Biochemistry

was better compared to the control group, indicating the high
wound-healing activity of the mushroom extracts [87].
5.1. Eects on Skin Melanoma. Skin melanoma, while
comprising only 5% of skin cancers, is notoriously aggressive
and often resistant to conventional therapies, driving the
exploration of novel anticancer agents [88]. Recent studies
have focused on the eective anticancer agents such as
bioactive compounds found in mushrooms [89]. Beta-
glucans, predominantly found in mushrooms such as shii-
take and Maitake have been shown to modulate the immune
system and inhibit the growth and proliferation of mela-
noma cells [90, 91]. Lectins as protein molecules, abundant
found in certain mushroom species can recognize and bind
specically to cancer cells, leading to their apoptosis (pro-
grammed cell death), thus curbing melanoma progression
[92]. Mushrooms like Ganoderma lucidum (Reishi) contain
triterpenoids that exhibit antiinammatory and antioxidant
activities, targeting melanoma cells and preventing metas-
tasis [92]. Potential mechanisms of mushrooms bioactives
against melanoma [91, 92]:
(i) Inhibition of cell proliferation by mushroom ex-
tracts, particularly from species like Agaricus blazei,
have demonstrated an ability to halt the pro-
liferation of melanoma cells, inducing cell cycle
arrest [91, 92]
(ii) Induction of apoptosis, mushroom-derived bio-
actives can activate the intrinsic apoptotic pathways
in melanoma cells, leading to cell death and pre-
venting tumor progression [91, 92]
(iii) Antimetastatic activity; certain mushrooms have
compounds that inhibit melanoma cell migration
and invasion, thereby curbing the metastasis, which
is a signicant challenge in melanoma management
[91, 92]
(iv) Immunomodulation; beta-glucans bolster the
body’s immune response against melanoma, en-
hancing the activity of macrophages and natural
killer cells, which play a role in targeting and
destroying cancer cells [91]
Liu et al. [93] investigated the in vivo antitumor and
antimetastatic activities of chloroform extract from Cordy-
ceps taii (CFCT). Male mice aged between 5 and 7 weeks,
average weight of 18.0 ±2.0 g, were injected with melanoma
B16F10. After the tumor growth, the mice were divided into
three groups for CFCT treatment according to the applied
dose of CFCT, which were 20, 50, and 100 mg/kg. A model
group was treated only with saline, and a combined ad-
ministration group was treated with 20 mg/kg CFCT and
20 mg/kg cyclophosphamide (CTX). e results showed that
the tumor growth of melanoma B16F10 in the mice group
treated with 100 mg/kg CFCT and the combined adminis-
tration was signicantly inhibited with CFCT treatment. e
antimetastatic activity of CFCT for melanoma B16F10 in
mice was observed by considering the common metastasis of
melanoma to lung tissue in mice. According to the results,
only the model group and the group treated with 20 mg/kg
CFCT showed a metastatic focus of melanoma B16F10,
indicating that CFCT was inuential in the inhibition of
melanoma metastasis in mice [93].
polyphenols
flavonoids
chitin, chitosan
polysaccharides
skin wound healingextracellular matrix generation
collagen production
E-cadherin
broblasts proliferation and
migration
MMP-2
keratinocytes proliferation
anti-inammatory
Figure 2: Illustrative scheme regarding the role of bioactive mushrooms in wound healing. Abbreviations and symbols: ↑increase,
↓decrease, MMP-9 (matrix metalloproteinase 9).
Journal of Food Biochemistry 11

In a similar in vivo study by Harhaji Trajkovi´
c et al. [94],
the tumor growth inhibition in inoculated C57BL/6 mice
with syngeneic B16 tumor cells was observed as a result of
treatment with methanol extract from Cariolus versicolor
(50 mg/kg) for 14 days. e direct focus on skin melanoma
in these studies substantiates the specic impact of
mushroom-derived bioactives on this form of skin cancer; as
research progresses, the translation of these ndings to
clinical applications could improve the treatment landscape
for skin melanoma. Figure 3 shows the antimelanoma eect
of mushrooms bioactive compounds.
5.2. Eects on Atopic Dermatitis. Atopic dermatitis (AD),
often referred to as eczema, is a chronic inammatory skin
disorder characterized by itchiness, redness, and a rash. AD
is induced by a combination of genetic, psychologic,
pharmacologic, environmental, and immunological factors.
ough its etiology is multifactorial, involving genetic,
environmental, and immunological factors, there’s been
a growing interest in alternative therapeutic agents, in-
cluding mushroom-derived bioactives, for its treatment and
management [95, 96]. Many mushrooms exhibit antiin-
ammatory activities, which are critical in managing atopic
dermatitis since inammation is a signicant contributor to
its pathogenesis [97]. For instance, polysaccharides extracted
from Ganoderma lucidum (Reishi mushroom) have dem-
onstrated the ability to suppress the expression of proin-
ammatory cytokines, potentially mitigating the
inammatory response associated with AD [97]. Skin barrier
dysfunction is also a hallmarking feature of atopic derma-
titis, and certain mushroom derivatives have been shown to
bolster the skin barrier. Chitin, a component present in the
cell walls of mushrooms, can be transformed into chitosan,
which is known for its moisturizing eect on the skin,
potentially helping to restore the skin barrier [98]. Itching
associated with AD can signicantly reduce the quality of life
for patients; mushrooms like Pleurotus ostreatus (oyster
mushroom) possess compounds that exhibit antipruritic
(antiitching) eects, oering potential symptomatic relief
[99]. An imbalance in immune responses is a critical aspect
of AD pathophysiology; many mushroom species are re-
nowned for their immunomodulatory eects. β-glucans,
which are abundant in mushrooms like shiitake (Lentinula
edodes), may modulate immune responses, thus potentially
oering therapeutic advantages for AD patients [99]. Oxi-
dative stress plays a pivotal role in the aggravation of atopic
dermatitis, and many mushrooms, such as the Cordyceps
species, are rich in antioxidants, which can counteract ox-
idative stress, further aiding in the alleviation of AD
symptoms [100]. Secondary bacterial infections are common
in AD lesions due to compromised skin integrity; mushroom
extracts like those from Agaricus bisporus (white button
mushroom) have shown antimicrobial properties, poten-
tially preventing or treating these secondary infections [101].
Watanabe et al. [96] examined the eects of hot water extract
of the mushroom Basidiomycetes-X (BDM-X) on atopic
dermatitis (AD) skin lesions in NC/Nga mice, which can
develop AD clinically very similar to humans. A cream is
used to cause AD-like skin lesions in mice; one-third was
kept untreated with the cream as the control group. e
reminder with skin lesions were divided into two groups,
one of which was treated with the BDM-X extracts. e
results showed that AD skin lesions in BDM-X-treated mice
were rapidly decreased, whereas the other group with AD
still had the skin lesions. is signicant result revealed the
high potential of BDM-X extracts in AD treatment [96].
Another study focusing on the treatment of AD, conducted
by Choi et al. [102], analyzed the ethanolic extract eciency
of Lentinula edodes, including polyphenols, avonoids,
β-carotene, and lycopene. e eight weeks old female BALB/
c mice were employed to investigate various eects of AD.
e AD lesion in mice ears was induced through exposure to
Dermatophagoides farinae extract (DFE) and 4-
dinitrochlorobenzene (DNCB). Mice were divided into
four groups: one with only AD lesions, another with AD
receiving 250 mg/kg L. edodes extract, a group with AD
receiving 500 mg/kg L. edodes extract, and the control group.
Two groups with AD receiving 500 mg/kg and 250 mg/kg
L. edodes extract showed considerably better results than
other groups within 28 days after the induction of AD.
Overall results indicated that L. edodes extract eectively
decreased several AD symptoms by reducing the severity of
AD lesions, cervical lymph nodes, and inammatory cyto-
kines in the ears of mice [102].
5.3. Eects on Hyperpigmentation. Hyperpigmentation, one
of the common skin disorders observed in all skin con-
ditions, including acne or atopic dermatitis, with various
symptoms such as dark spots, darker skin, and irregular
grey patches, can be treated with depigmentation agents
[103, 104]. e therapeutic potential of mushroom bio-
actives in addressing hyperpigmentation has been a subject
of growing research interest; certain mushroom extracts
have demonstrated inhibitory eects on tyrosinase, the key
enzyme responsible for melanin synthesis. For instance,
Agaricus bisporus (white button mushroom) contains
compounds that have been found to inhibit tyrosinase
activity, thus potentially reducing melanin production and
aiding in the treatment of hyperpigmentation [105]. Oxi-
dative stress is one of the factors that can trigger or ex-
acerbate hyperpigmentation. Many mushrooms, such as
Ganoderma lucidum (Reishi mushroom), are rich in an-
tioxidants that can combat oxidative stress, oering a two-
pronged approach to addressing both melanin production
and the underlying triggers [92]. Inammation-induced
hyperpigmentation, or postinammatory hyperpigmenta-
tion (PIH), is a common concern following acne, skin
injuries, or inammatory skin conditions. Mushrooms like
Cordyceps and shiitake (Lentinula edodes) exhibit anti-
inammatory properties, which might help in reducing the
occurrence or severity of PIH [45]. Some mushroom ex-
tracts can promote an even skin tone and improve overall
skin radiance. A healthy skin barrier is crucial for pre-
venting external triggers, like UV radiation and
12 Journal of Food Biochemistry

environmental pollutants, from inducing hyperpigmenta-
tion; components like beta-glucans, present in several
mushrooms, can bolster the skin’s barrier function [106].
Trametes versicolor, also known as the Turkey tail mush-
room, has been incorporated into skincare products for its
potential skin-brightening eects [106]. Given their mul-
tifaceted action on skin health, mushroom bioactives might
enhance the ecacy of other depigmenting agents or
treatments; they could be incorporated into comprehensive
treatment regimens for hyperpigmentation, ensuring more
holistic care [106]. An in vivo study conducted by Pavic
et al. [107], explored the toxicity of antimelanogenic
compounds found in mushrooms to inhibit excessive skin
pigmentation. e zebrash was preferred as the preclinical
experimental model to evaluate the toxicity by carrying six
dierent doses of ethanol extracts of each of the ve
mushrooms for ve days. e results revealed the toxicity
of ve selected mushroom extracts subjected to application
doses. e greatest toxicity proles have been achieved for
Laetiporus sulphureus (LSE) and Agaricus silvaticus (ASE),
which were not toxic at high doses of up to 400–500 mg/
mL. In contrast, the remaining three extracts were detected
as possibly toxic and unsafe for humans. is study showed
that the tyrosinase activity and melanin synthesis in
zebrash were inhibited by LSE and ASE extracts without
inammatory, immunosuppressive, or toxic eects, in-
dicating their safety for possible usage in cosmetics and
other applications [107]. Generally, mushroom-derived
bioactives have exhibited a favorable safety prole when
compared to some chemicals often used to treat hyper-
pigmentation, and this makes them attractive alternatives,
especially for individuals with sensitive skin. e most
representative pharmacological studies on the therapeutic
potential of mushrooms against dierent skin diseases and/
or skin disorders are summarized in Table 3.
6. Clinical Studies Related to Bioactive
Compounds of Mushrooms and SDDs
Several investigations on the eects of dierent mushroom
extracts and/or their bioactive compounds on skin condi-
tions and aging processes are found in the literature.
Yamamoto and Kimura [23] investigated the mushroom
Sparasis crispa (SC) in terms of its therapeutic eects on skin
conditions in humans. To understand the eects of SC on
skin conditions in humans, 26 healthy volunteers, between
the ages of 20 and 60 years, were divided into two groups:
orally SC-administered and placebo. According to the re-
sults obtained after four weeks, the cheek transepidermal
water loss was considerably lower in the SC-administered
group than in the placebo group. us, it supported the
positive eect of SC administration on improving human
skin conditions [23]. Another recent clinical study was
conducted by Lee et al. [123] to investigate the antioxidant,
anti-inammatory, antiallergic, antidiabetic, and anti-
angiogenic eects of veratric acid derived from the mush-
room Sparassis crispa and demonstrate its clinical eects. A
cream including veratric acid isolated from Sparassis crispa
and the control was applied for 12 weeks on the right and left
periorbital areas of 20 women, average of 47.7 ±4.8 years old.
e results showed that the veratric acid extract improved
facial wrinkle formation from Sparassis crispa by increasing
skin melanoma
tumor initiation tumor growth
metastasis
synergistic efect with
cytostatic drugs
β-glucans
triterpenoids
lectins
Figure 3: Antimelanoma eect of mushrooms bioactive compounds. Symbol: ┴inhibition.
Journal of Food Biochemistry 13

Table 3: Summary of preclinical studies on animal models about the therapeutic potential of mushrooms on SDDs.
Mushroom species and
their extracts
Types of skin
diseases and/or disorders Eect Results References
Mannogalactan from Pleurotus eryngii (cold
aqueous extraction)
Melanoma (skin cancer)
Anticancer
60% reduction of the tumor volume in
melanoma-bearing C57BL/6 mice with the treatment
of mannogalactan (50 mg/kg) compared to the
control group
[108]
Choloroform extract of Cordyceps taii
(methanol extraction)
Considerable in vivo potential of antitumor and
antimetastatic activities probably due to its
antiproliferation, antioxidant, and
immunoregulatory eects
[93]
Extract of bioactive compounds from
Pleurotus ferulae (ethanol extraction)
↓tumor formation, ↓growth, size, and nal weight of
tumor in vivo with prevention of tumor cell
proliferation [109]
↓cell migration, ↑apoptosis
CARI III (dietary supplement) is composed
of Phellinus linteus,Inonotus obliquus,
Antrodia camphorata, and Ganoderma
lucidum (CARI, Inc., Seoul, South Korea)
↓tumor weight with the treatment of 300 mg CARI
III/kg/day compared to the treatment of doxorubicin
(Dox) [110]
↑life span (50.88%) in the CARI III-administered
animal group comprising the tumor control animal
group
Methanol extract including total terpenoids
and puried methanol extract including
mainly acidic terpenoids from Ganoderma
lucidum (methanol extraction)
↓tumor growth in vivo with the treatment of both
extract types obtaining a more potent eect with
methanol extract including total terpenoids than
puried methanol extract including mainly acidic
terpenoids [94]
14 times lower tumor volume in the group of
B16-melanoma-bearing mice with the treatment of
methanol extract, including total terpenoids,
compared to control tumor-bearing mice
Extracts of Cordyceps sinensis (extraction
with petroleum ether, ethyl acetate, ethanol
and hot water)
Anticancer/Antitumor
↓B16-induced melanoma in C57BL/6 mice and
approximately 60% reduction of tumor size more
than 27 days with ethyl acetate extraction
[111]
Acidic polysaccharide from Phellinus linteus Antimetastatic
↓melanoma cell metastasis in mice
[112]
↓adhesion, ↓invasion of cancer cells through the
extracellular matrix not directly inuential on the
growth of cancer cell
14 Journal of Food Biochemistry

Table 3: Continued.
Mushroom species and
their extracts
Types of skin
diseases and/or disorders Eect Results References
Hot water extract of Ganoderma lucidum Skin wounds Wound healing/Antioxidant
e highest wound closure in streptozotocin-induced
diabetic rats with the treatment of 10% (w/w)
aqueous extract cream compared to treated groups
with Intrasite gel (positive control) and aqueous
cream (negative control)
[113]
e shortest reepithelization period with the
treatment of 10% (w/w) aqueous extract cream
Considerable higher in vivo antioxidant activity with
15% (w/w) aqueous extract compared to negative and
positive control groups
Lower oxidative protein products and lipid damage
in treated diabetic rats with aqueous extract
compared to negative and positive control groups
Extract of Cantharellus cibarius Skin wounds (circular excision and
linear incision wound models)
Wound healing/
Antiinammatory
↑healing activity for treated rats with extract of
C. cibarius, and Madecassol (reference drug)
compared to nontreated and vehicle-treated rats
completely repairing the epidermal layer, increasing
collagen production, considerable neovascularization
and epithelization degree in the treated rats with the
extract
[114]
↓COX-2 in treated rats with extract than in
nontreated and vehicle-treated rats
Extract of Antrodia camphorate (ethanol
extraction) Skin wounds (excision model) Wound healing/
Anti-inammatory
↑wound healing closure in treated rats with extract
(for both doses of 100 mg/kg and 200 mg/kg) and
Intrasite gel (reference drug) compared to treated rats
with vehicle [115]
Considerably less scar width at wound closure and
less inammatory cells, more collagen, and more
broblast in granulation tissue with extract treatment
than vehicle treatment
Journal of Food Biochemistry 15

Table 3: Continued.
Mushroom species and
their extracts
Types of skin
diseases and/or disorders Eect Results References
Aqueous lyophilized extract of Ganoderma
lucidum
Skin wounds
Wound healing
↑healing activity with an increase in wound
contraction, accumulation of collagen, hexosamine,
and total protein content for treated rats with extract
[80]
Sparassis crispa
↑wound closure in streptozotocin-induced diabetic
rats with oral administration of S. crispa
[116]
↑migration of macrophage and broblast,
↑regeneration of collagen, and epithelialization with
S. crispa treatment compared to the control group
(nontreated with S. crispa)
Aqueous extract of Hericium erinaceus Wound healing
Higher and quick wound healing in rats treated with
the extract and Intrasite gel than in rats treated with
sterilized distilled water
[117]Considerably less scar width in healed wound area
and lower macrophages and higher collagen in the
healed wound for treated rats with extract than
treated rats with sterilized distilled water
16 Journal of Food Biochemistry

Table 3: Continued.
Mushroom species and
their extracts
Types of skin
diseases and/or disorders Eect Results References
Extract of Hypsizigus marmoreus (ethanol
extraction)
Atopic dermatitis
Antiatopic dermatitis/
Antiinammatory
↓severity score of dermatitis and the epidermis
thickness in treated BALB/c mice group with extract
for ve weeks compared to another treated group
with PCL
[95]
↓IL-1β,↓IFN-cproduction levels in concanavalin
A-stimulated and lipopolysaccharide-stimulated
mouse splenocytes and macrophages with extract
treatment
↑IL-4 with administration of extract to splenocytes of
mouse
Aqueous extract of Cordyceps militaris Antiatopic dermatitis/
Antiinammatory
↓epidermal and dermal thickness and inltration of
mast cell in ears of DFE/DNCB-induced BALB/c
mice group with oral administration of the extract [118]
↓immunoglobulin levels and gene expression of T
helper ()1/2 cytokines in the tissue of mouse ear
with extract
Extract of Lyophyllum decastes Antiatopic dermatitis/
Antiallergic
↓AD-like skin lesions development according to low
scores of total skin severity and levels of
immunoglobulin E in NC/Nga mice with oral
administration of the extract
[119]↓IL-4, no inhibition of IFN-cproduction with extract
treatment
Exertion of antiallergic action due to suppression of
serum IgE and 2-type immune responses with
extract treatment
Aqueous extract of Grifola frondosa Antiatopic dermatitis/
Anti-inammatory
↓score of dorsal skin dermatitis with extract
treatment
[89]
↓AD-like skin lesion, ↓-1/-2 response in NC/
Nga mice with extract treatment
Synergistic eect in AD-like skin lesions by reduction
of serum IgE, mast cells inltration, and cytokines
expression with combined treatment of extract and
dexamethanose
Journal of Food Biochemistry 17

Table 3: Continued.
Mushroom species and
their extracts
Types of skin
diseases and/or disorders Eect Results References
Extracts of Pleurotus eryngii Antiatopic dermatitis/
Antiinammatory/Antiallergic
↓AD-like skin lesions in DNCB-induced NC/Nga
mice with continuous extract treatment
[120]
↓severity of dermatitis, ↓IgE and thymus and
activation-regulated chemokine (TARC), and mRNA
expression of TNF-α, INF-c, IL-4, IL-5, and IL-13 in
mice with extract treatment
↓dermis and dermal inltration thickness of
inammatory cells and mast cells with extract
treatment
↓allergic contact dermatitis due to modulation of T
helper 1 and 2 responses and decrease of the
inammatory cells and mast cells inltration in the
skin lesions in NC/Nga mice
Extract of Ganoderm A formosanum
(ethanol extraction)
Abnormality of skin pigmentation
Antityrosinase/
Antimelanogenesis
↓surface pigmentation level on the body of zebrash
with extract treatment after 48 h due to considerable
reduction of tyrosinase activity and melanin content
[121]
No signicant dierentiation in terms of morphology
and mortality of treated zebrash with extract
compared to the control group
Less toxicity and similar eciency for
depigmentation with extract treatment in lower
dosages than kojic acid treatment
Extract of Antrodia cinnamomea (ethanol
extraction)
Antityrosinase/
Antimelanogenesis
↓hyperpigmentation, ↓tyrosinase activity
[122]
↓melanin formation activity for treated zebrash with
extract
Less toxic eect and similarly eective
depigmentation of zebrash with extract treatment at
a lower dosage (50 ppm) compared to kojic acid
(1400 ppm)
Note:↑increase, ↓decrease, AD (atopic dermatitis), IL (interleukin), Interferon-gamma (IFN-c), TARC (thymus and activation-regulated chemokine), TNF-α(tumor necrosis α).
18 Journal of Food Biochemistry

cell proliferation, inhibiting the collagen decrease in the
dermis, increasing tissue inhibitors of metalloproteinases,
and increasing laggrin against UV radiation [123]. Al-
though several studies indicated that mushrooms have
therapeutic potential on several skin diseases, more in vivo
and clinical studies should be performed to understand the
working mechanisms of the mushroom extracts in both
animal and human body and their eects on the whole-body
system.
7. Allergic Contact Dermatitis
Caused by Mushrooms
Among allergic dermatitis as skin side eects caused by
mushrooms, the most common and well-known is that
caused by the shiitake. Dermatitis produced by the shiitake
fungus is characterized by skin eruptions due to a toxic
reaction to lentinan, a thermolabile polysaccharide. Naka-
mura rst described shiitake dermatitis in 1977, when he
reported 23 cases of people who consumed the fungus and
presented erythematous lesions, reminiscent of self-
agellation from the Middle Ages [124]. In Japan, shiitake
dermatitis is traditionally associated with the consumption
of shiitake mushrooms. Although shiitake mushroom
generates this dermatitis because lentinan is thermolabile, its
toxicity can be avoided if the mushroom is consumed
cooked [125]. Shiitake dermatitis is a rare skin reaction to
lentinan, a polysaccharide component in the cell walls of
shiitake mushrooms (Lentinula edodes). Lentinan is a β-
(1 ⟶3)-d-glucan. Lentinus edodes corresponds to a bi-
ologically active macromolecule with remarkable anticancer
activity, which is given through the activation of the human
immune system [126]. It has been shown that the chemical
structure of lentinan is β-(1 ⟶3)-d-glucan which has 2
(1 ⟶6)-glucopyranoside branches for every ve linear
(1 ⟶3)-β-glucopyranoside linkages, which can be char-
acterized instrumentally by techniques such as high-
performance liquid chromatography (HPLC), FITT, and
nuclear magnetic resonance (NMR). Additional cases of
hypersensitivity reactions to mushrooms have been docu-
mented. For instance, contact dermatitis has also been re-
ported after handling or ingesting other mushroom species,
such as the common button mushroom (Agaricus bisporus)
and other edible varieties [13, 127]. ese reactions are
typically characterized by pruritic and eczematous erup-
tions, which are histologically similar to shiitake dermatitis,
suggesting a common immunological pathway in the hy-
persensitivity response to dierent mushroom species [128].
Other instances include reports of airborne contact der-
matitis from spores of various mushroom types, which can
occur in both occupational settings, such as mushroom
farming, and in environments with high spore concentra-
tions [127]. ese reactions can be more complex, involving
respiratory symptoms alongside dermatological manifesta-
tions, illustrating the diverse immunological challenges
posed by mushroom bioactives [127]. To address these
adverse reactions comprehensively, it is crucial to investigate
the full spectrum of immunogenic components in mush-
rooms, their potential cross-reactivity with other allergens,
and the conditions under which they become pathogenic.
Further research into the identication of specic allergenic
proteins and polysaccharides, as well as their mechanisms of
action, will be vital in developing preventive strategies and
therapeutic interventions for mushroom-related hypersen-
sitivity reactions [129].
8. Therapeutic Perspectives, Limitations,
and Challenges
8.1. Insights into Mushroom-Derived Compounds for SDDs
Management/Prevention. e nuanced roles of mushroom-
derived compounds in skin health are increasingly evident,
with several key mechanisms oering therapeutic avenues
for SDD management and prevention:
Beta-glucans and immune modulation: beta-glucans,
prevalent in varieties like shiitake and maitake, have been
shown to enhance the skin’s immune defense by activating
dendritic cells and macrophages, leading to a more robust
response to pathogenic challenges and potentially reducing
the incidence and severity of inammatory skin conditions
[128]. Triterpenoids and inammatory pathways: the tri-
terpenoids present in Reishi mushrooms exhibit an ability to
modulate inammation through the suppression of NF-kB
activation, which could play a role in mitigating chronic
inammatory states associated with conditions such as
psoriasis and atopic dermatitis [130, 131]. Antioxidant
phenolics and skin integrity: the antioxidant properties of
phenolic compounds in mushrooms like Chaga may protect
dermal broblasts from oxidative stress, thus preserving skin
integrity and preventing the premature aging associated with
oxidative damage [17]. Lectins and tumor inhibition: certain
mushroom lectins demonstrate specicity in binding to
aberrant cell membranes, initiating apoptosis, and poten-
tially oering a targeted approach to managing melanoma
and nonmelanoma skin cancers [6]. Ergothioneine and
mitochondrial protection: ergothioneine has shown promise
in protecting skin cells from mitochondrial DNA damage
induced by UV radiation, suggesting a role for this com-
pound in the prevention of photoaging and photocarcino-
genesis [7]. ese detailed mechanistic pathways highlight
the potential of mushroom bioactives as adjunctive or al-
ternative therapies in the management and prevention of
various SDDs. Continued research in these areas may yield
signicant advancements in dermatological treatments.
8.2. Cytotoxicity and Allergenicity Eects of Mushroom
Bioactives. e therapeutic benets of mushrooms are
balanced by a need to understand their potential cytotoxic
and allergenic eects [48]. Research into various mushroom
species has revealed a spectrum of bioactive compounds
with diverse biological activities, some of which may exhibit
cytotoxicity and allergenicity under certain conditions [48].
For example, compounds such as hydrazine derivatives
found in certain edible mushrooms have shown cytotoxic
properties, which could pose a risk if consumed in large
quantities or if the mushrooms are not properly processed
[132]. Similarly, the potential allergenicity of mushrooms is
Journal of Food Biochemistry 19

an area of ongoing research, with instances of hypersensi-
tivity reactions documented in susceptible individuals upon
exposure to specic mushroom species [132]. e cytotoxic
eects of mushrooms are often a result of their defense
mechanisms, producing compounds that can be harmful to
cells. While these properties can be leveraged in ghting
cancer cells, as with the antitumor eects of polysaccharide-
K (PSK) extracted from Trametes versicolor [14], they may
also cause adverse eects in nontarget cells. It is, therefore,
crucial to characterize these eects fully to mitigate risks
associated with mushroom consumption or therapeutic use.
Allergenicity, on the other hand, may manifest as hyper-
sensitivity reactions, such as contact dermatitis or re-
spiratory allergies, particularly in occupational settings or
among mushroom cultivators [13, 127]. For instance, shii-
take mushroom dermatitis is a well-documented condition
caused by lentinan, a polysaccharide that can trigger an
inammatory response upon skin contact [128]. Recent
investigations into these eects have emphasized the im-
portance of identifying the molecular mechanisms un-
derlying these responses. Techniques such as proteomics and
immunoblotting have been employed to pinpoint the spe-
cic mushroom proteins that elicit immune reactions [133].
Furthermore, understanding the role of mushroom-derived
compounds in modulating the immune system can provide
insights into mitigating allergenic responses while pre-
serving their health benets [15]. Overall, while mushrooms
are a rich source of bioactives with signicant health ben-
ets, it is imperative to balance their therapeutic potential
with safety considerations. Ongoing research and rigorous
clinical trials are necessary to elucidate the full scope of
cytotoxic and allergenic eects posed by mushroom bio-
actives and to establish guidelines for safe consumption and
therapeutic application.
8.3. Limitations, Challenges, and Clinical Pitfalls. e po-
tential therapeutic properties of mushroom bioactives have
stirred considerable interest in the dermatological com-
munity. However, like all emerging treatments, there are
limitations, challenges, and potential pitfalls that need to be
acknowledged. Much of the evidence supporting the ecacy
of mushroom bioactives in skin therapy comes from in vitro
studies or in vivo animal models, but the number of ran-
domized controlled trials in humans is still limited, neces-
sitating further research to conrm ecacy, safety, and
optimal dosing. Variability in mushroom composition de-
pend on factors such as growth conditions, harvesting time,
and postharvest processing, the bioactive compound prole
of a given mushroom species can vary signicantly and this
poses challenges in ensuring consistent therapeutic eects.
Other species of mushrooms can cause allergic contact
dermatitis or other hypersensitivity reactions; identifying
and categorizing allergenic mushrooms are crucial, espe-
cially when recommending topicals containing mushroom
extracts. Some mushroom bioactives might interact with
other medications, either enhancing or inhibiting their ef-
fects; this can be particularly concerning for patients on
multiple medications or those with underlying health
conditions. e method used to extract bioactives from
mushrooms can signicantly inuence their potency and
therapeutic value; standardizing these methods is crucial for
ensuring consistent results and safety proles. While many
mushroom bioactives have been deemed safe for short-term
use, long-term safety data is often lacking; potential cu-
mulative eects or long-term side eects must be assessed
through extended clinical trials. e surge in interest sur-
rounding “natural” treatments might lead some individuals
to self-prescribe mushroom-based remedies without proper
guidance, risking incorrect dosages, potential side eects, or
suboptimal outcomes. Also, challenges persist in the utili-
zation of mushroom extracts and their associated metabo-
lites as ingredients in cosmeceutical and nutricosmetic
products; these challenges range from optimizing extraction
processes, validating ecacy and safety claims, using
microcarriers and nanocarriers for controlled release, and
weighing the advantages and disadvantages of using extracts
versus individual compounds [103]. Despite these clinical
challenges, the diverse biomolecules contained in mush-
rooms oer a sustainable option for developing cosme-
ceutical and nutricosmetic formulations, although more
research is needed to address concerns regarding stability,
compatibility, safety assessments, and toxicological studies
[103]. Given the vast number of mushroom species and their
bioactives, regulatory agencies might nd it challenging to
evaluate and categorize each one; this can lead to delays in
approvals or inconsistencies in quality control. Researching,
developing, and standardizing mushroom-based treatments
can be expensive; these costs might be passed on to patients,
limiting access to these treatments, especially in regions
where insurance does not cover alternative therapies.
Careful and rigorous scientic evaluation is vital to harness
their potential while ensuring patient safety and optimal
therapeutic outcomes.
9. Overall Conclusions and Future Prospects
Dierent biologically active compounds, including poly-
saccharides, proteins, peptides, vitamins, minerals, dietary
bers, alcohols, terpenoids, and phenolics, are present in
mushrooms. ese compounds exhibit antidiabetic, anti-
obesity, anticancerous, antitumor, anti-inammatory, an-
timicrobial, antiviral, antiallergic, antiaging, antiwrinkle,
antioxidant, immunomodulating, hepatoprotective, hypo-
glycemic, and skin whitening activities. Dierent skin
problems-induced by inammation and the high activity of
free radicals can be treated with mushroom extracts with
antioxidant and anti-inammatory activities. In addition,
extracts of bioactive compounds from mushrooms with anti-
inammatory, antioxidant, photoprotective, antityrosinase,
antielastase, and anticollagenase activities can reduce the
severe eects of inammatory skin diseases, providing
photoprotection and correcting skin hyperpigmentation.
erefore, mushrooms are considered essential and original
ingredients for developing new pharmaceutical products
due to their health benets and protective activities against
dierent SDDs. After exploring their therapeutic and/or
healing potentials against dierent types of diseases across
20 Journal of Food Biochemistry

dierent in vitro,in vivo, and clinical studies, it has been
observed that mushrooms have attracted signicant atten-
tion from researchers in recent years. Fungal compounds
from large mushrooms Basidiomycetes species present
several biological activities such as antioxidant, antiin-
ammatory, and antimicrobial, some associated with
pharmaceutical, cosmeceutical, and nutricosmetic potential,
in in vitro and in vivo studies. However, ethnobotanical/
ethnopharmacological data shows a limited number of
mushroom species related to the treatment of skin diseases.
Mainly polysaccharides, followed by phenols, avonoids,
fatty acids, and tocopherols, from fungal species Agaricus
spp., Auricularia spp., Lentinus spp., and Pleorotus spp.
(among other mushroom species), showed antioxidant ac-
tivity. e metabolisms of several mushroom species present
antimicrobial activity against a wide variety of fungi, Gram-
positive, and Gram-negative bacteria including Staphylo-
coccus aureus, Salmonella enteritidis, and Escherichia coli.
e results obtained from scientic studies revealed the
potential antiageing eects of the enzyme-assisted extract
mushroom Agaricus bisporus and their puried forms with
reduction of the lipid peroxidation, increasing the antioxi-
dant enzymes, improving the organ functions, and enabling
the lipid metabolism. e antimicrobial activity of fungal
extract depends upon genetic factors and environmental
conditions that can inuence the metabolic pathway that
allows the production of these phytochemicals. Mushroom
chitin and chitosan play a key role in the treatment of
wounds by accelerating the proliferation of broblast, ker-
atinocytes, and polysaccharides. Some fungi species can
cause dermatitis or supercial mycosis. Many scientic
studies have demonstrated the natural antioxidant potential
of mushrooms. eir extracts rich in a wide variety of
metabolites, could be incorporated, for example, as dietary
supplements to complement the natural production of an-
tioxidants at a cellular level. In summary, dierent mush-
room compounds as polysaccharides, proteins, peptides,
vitamins, minerals, dietary bers, alcohols, terpenoids, and
phenolics present in vitro and in vivo biological activities for
potential use on several skin diseases. However, greater
biomedical and clinical studies are necessary to prove these
preliminary data.
Data Availability
e data used to support the ndings of this study are in-
cluded within the article.
Conflicts of Interest
e authors declare that they have no conicts of interest
that could have appeared to inuence the work reported in
this paper.
Authors’ Contributions
All authors contributed and made signicant contributions
to the work reported, whether that is in the conception,
study design, execution, acquisition of data, analysis, and
interpretation, or all these areas—that is, revising or criti-
cally reviewing the article; giving nal approval of the
version to be published; agreeing on the journal to which the
article has been submitted; and conrming to be accountable
for all aspects of the work. All authors have read and agreed
to the published version of the manuscript.
Acknowledgments
e authors would like to express their gratitude to Dr. Irina
Zamr, MD, RCP London, Basildon University Hospital,
UK, for providing professional English editing of this
manuscript and for editorial support.
Supplementary Materials
Details of phytochemicals in mushrooms are provided in the
supplementary le. (Supplementary Materials)
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