Next Article in Journal
Maillard Reaction Products in Gluten-Free Bread Made from Raw and Roasted Buckwheat Flour
Previous Article in Journal
The Influence of Smoking Status on Exhaled Breath Profiles in Asthma and COPD Patients
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 26
Issue 5
10.3390/molecules26051359
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Mushroom-Derived Bioactive Molecules as Immunotherapeutic Agents: A Review

by
Dinesh K. Patel
1,†,
Sayan Deb Dutta
1,†,
Keya Ganguly
1,
Seong-Jun Cho
2 and
Ki-Taek Lim
1,*
1
Department of Biosystems Engineering, College of Agriculture and Life Science, Kangwon National University, Chuncheon 24341, Korea
2
Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon 24341, Korea
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2021, 26(5), 1359; https://doi.org/10.3390/molecules26051359
Submission received: 22 January 2021 / Revised: 25 February 2021 / Accepted: 26 February 2021 / Published: 4 March 2021
(This article belongs to the Section Food Chemistry)
Browse Figures
Versions Notes

Abstract

:
Mushrooms with enhanced medicinal properties focus on finding such compounds that could modulate the human body’s immune systems. Mushrooms have antimicrobial, antidiabetic, antiviral, hepatoprotective, antitumor, and immunomodulatory properties due to the presence of various bioactive components. β-glucans are the major constituent of the mushroom cell wall and play a significant role in their biological activity. This review described the techniques used in the extraction of the active ingredients from the mushroom. We highlighted the structure of the bioactive polysaccharides present in the mushrooms. Therapeutic applications of different mushrooms were also described. It is interesting to note that mushrooms have the potential sources of many bioactive products that can regulate immunity. Thus, the development of functional medicinal food based on the mushroom is vital for human welfare.

1. Introduction

Mushroom, a fungi kingdom member, has drawn significant interest in medicinal applications due to their anti-inflammatory, antimicrobial, antidiabetic, cardiovascular-protective, hepatoprotective, and anticancer potentials. It regulated the immune system, and macrophages, T cells, dendritic cells (DC), natural killer (NK) cells, and hematopoietic stem cell activities by phagocytic activity, generating reactive oxygen species, inflammatory mediators, and cytokines production [1,2,3,4]. Mushroom is a rich source of proteins, fibers, and vitamins. It is challenging to distinguish between edible and medicinal mushrooms because many edible mushrooms have therapeutic properties, and many medicinal mushrooms are also edible [5,6,7,8]. Approximately 1.5–5.0 million fungi species are known globally, and among them, a few hundred species have medicinal properties [9]. Agaricus bisporus, Lentinulla edodes (shiitake), Pleurotus ostreatus (oyster mushroom), Flammulina velutipes (golden needle mushroom or enokitake), Grifola frondosa (maitake), and Volvariella volvacea (straw mushroom) are commonly used mushrooms worldwide [10]. Chitin and β-glucans are two major constituents of the mushrooms’ cell wall, and out of these, the β-glucan, β-(1 → 3), β-(1 → 4), and β-(1 → 6) make mushrooms a vital material to use as therapeutic agents [11,12,13]. It also contains polysaccharides, polysaccharide–protein complexes, polyphenols, terpenoids, agaritine, ergosterol, and selenium in its structure [14]. Table 1 represents the specific constituents present in different mushrooms. Glucan, heterogeneous polysaccharides, is linked with the large numbers of glucose units. β-glucans derived from different sources have different branching, a branch linkage, and a backbone linkage in their structure that affect biological activity. Therefore, it is necessary to identify and characterize β-glucans with better therapeutic and immune-stimulatory activities [15]. Glucan stimulated the defense responses against infections and cancer [16,17,18]. Additionally, glucan reduced the stress and cholesterol level, hypoglycemic effects, and ulcerative colitis improvements [19,20,21]. Phagocytic cells play significant roles in antitumor activity through their phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and cytokine secretion process. Cytokines and chemokines regulated individuals’ homeostasis via cell differentiation, proliferation, apoptosis, inflammatory reactions, and immune responses [22]. Cytokines are low-molecular-weight proteins and regulate the intensity and duration of the immune response. However, chemokines are small polypeptides and regulate cell migration, adhesion, and activation of the leukocyte. Functional pleiotropy and redundancy are the characteristic features of the generated cytokines that contain interferons, different stimulating and growth factors, and interleukins (IL) [23]. Cytokines may act as a proinflammatory or anti-inflammatory factor, or both, depending on the local conditions of the target cells [24]. IL-1β, TNFα, IL-6, IL-15, IL-17, and IL-18 cytokines exhibited an inflammatory response, whereas IL-4, IL-10, and IL-13 showed anti-inflammatory potential [25].
The productions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6, IL-1), and interferon-γ (IFN-γ) cytokines have also been observed in the presence of β-glucans by activating the macrophages cells [26,27]. The antitumor activity of mushroom-derived nonstarch polysaccharides (NSPs) is mediated by the immune system of the host rather than direct action on cells [28]. Herein, we briefly discussed the therapeutic potential of commonly used mushroom extract or its derivatives. Mushrooms are enriched with many essential amino acids, polysaccharides, and vitamins necessary for human health. Therefore, mushrooms can be directly used in the human diet to enhance health due to different bioactive compounds.

2. Extraction of the Bioactive Components from Mushrooms

It is well-known that mushroom contains several active components, such as essential amino acids, proteins, vitamins and minerals, fiber, and polysaccharides in their fruiting bodies [29]. β-d-glucan polysaccharides and their derivatives extracted from mushrooms showed immunomodulatory responses [4,30]. Mushroom extracts also exhibited antitumor, antimicrobial, and antiviral potentials [31]. Therefore, it is essential to extract these active ingredients from the mushroom bodies to examine their therapeutic potential. The hot aqueous medium and aromatic solvent process are commonly used to extract bioactive polysaccharides from the mushroom. Here, we describe the extraction process of bioactive components by considering some conventional and modern methods.

2.1. Hot Water Extraction

In this method, the mushroom bodies are treated with distilled water and ethanol to remove the samples’ contamination. After that, the extraction of polysaccharides is performed by reacting the cleaned and pulverized mushroom with an alkaline solution (4% NaOH). The reaction media are kept at 4 °C for 12 h. The extracted media are separated by centrifugation or filtration, followed by precipitation with ethanol. The precipitated material is isolated and dialyzed via a cellulose bag to remove the excess alkali and other small molecules. The obtained material is separated and freeze-dried for further analysis. In some cases, a hot ethanol solution has been used to extract polysaccharides rather than an alkaline solvent or hot water. This method has been used in Termitomyces eurhizus, Grifola frondosa, Pleurotus tuber-regium, and Agaricus bisporus to extract bioactive components [32,33].

2.2. Organic Solvent Extraction

In this process, a low-boiling-point organic solvent, such as hexane, is selected to extract bioactive polysaccharides. In brief, the tested mushroom is cleaned and dried. The dried mushroom powder is treated with an appropriate organic solvent at room temperature and left for a week. After that, the filtrate is separated from the mother liquor and concentrated by a rotary evaporator. The obtained material is kept at 4 °C in a dark bottle for further applications. This method has been applied in Grifola frondosa, Hericium erinaceum, Agaricus blazei, Ganoderma lucidum, Coriolus versicolor, and Phellinus linteus for the extraction of bioactive components [34].

2.3. Soxhlet Method

In this method, the Soxhlet apparatus is attached to the extraction bottle to isolate bioactive components from mushrooms. The aqueous or organic solvents are utilized for the extraction. Here, the solvent is heated up to its boiling point, and the condensed vapors are collected in a flask. This process is repeated several times as desired. This method has been applied in Bauhinia variegate, Sanguisorba officinalis, and Tribulus terrestris to isolate bioactive components [35].

2.4. Ultrasound-Mediated Extraction

In this method, the extraction medium is placed in an ultrasound environment to generate the bubble within the solvent. These bubbles interrupt the plant cell wall and facilitate the solvent inside the plant material. The bioactive components come out due to the interruption of the cell wall and penetration of the solvent. This is a very effective extraction method and has several advantages. Here, a shorter extraction time, low amounts of solvent, and energy are required for the extraction [36].

2.5. Supercritical Fluid Extraction

Supercritical fluid extraction is an effective and eco-friendly extraction method applied for isolating a wide range of bioactive components. Carbon dioxide is the most suitable solvent isolating lipids, fat, and other nonpolar components. The polar solvents such as ethanol, methanol, and dichloromethane are added to a supercritical fluid to enhance the solubility [37]. A supercritical state is achieved when the temperature and pressure of the fluid surpassed its critical point.

2.6. Accelerated Solvent Extraction

The accelerated solvent extraction method is applied to extract various bioactive components under high temperature and pressure without reaching the solvent’s critical point. This method is also known as pressurized fluid extraction (PFE), high-pressure solvent extraction (HPSE), or enhanced solvent extraction (ESE). Methanol, ethanol, or mixtures of the solvents are used in this method. Significantly less time is required to extract bioactive compounds via this method than the others [35].

3. Linkage in Glucan

Polysaccharides are biologically active biopolymers composed of sugar units such as glucose, galactose, mannose, and fructose in different fashions. The sustainably and economically high yield of polysaccharides is produced from the microbial biomass under controlled fermentation conditions. Various polysaccharides have been extracted from the different mushrooms. The mushroom-derived polysaccharides have received substantial attention due to their superior health benefits activities such as anti-inflammatory, anti-oxidative, immunomodulatory, and hypolipidemic properties [38,39]. Mushroom-extracted bioactive polysaccharides have unparalleled applications in many fields, including food supplements, biomedicine, and cosmetic industries [40]. β-(1 → 3)/β-(1 → 6)-d-glucan and α-(1 → 3)-d-glucan are the most bioactive components present in the mushroom extract, and the structure of β-(1 → 3)/β-(1 → 6)-d-glucan is given in Figure 1. β-glucans have more immunomodulatory potential than α-glucan. Moreover, the α-glucan immunomodulatory activity can be improved by chemical functionalization [41,42].

4. Therapeutic Applications of Mushroom

4.1. Antitumor Activity

Yeast, grain, mushrooms, ginseng, jimson weed, cinnamon bark, ephedra, garlic, onion, and chamomile are often applied to treat or prevent diseases during the evolution of human history [43,44,45,46,47,48]. Among them, mushrooms have received a considerable amount of interest to use in the biomedical area due to their inheritance properties. Mushrooms are commonly used as a dietary supplement. Grifola frondosa (maitake) is an edible mushroom and used as a dietary supplement to promote human health. The maitake extract showed better T-cell activity by accelerating the Th-1 response in tumor-bearing mice and induced the natural killer cell (NK). It also stimulated the dendritic cell (DC) maturation [43,49,50]. Cancer, one of the most severe diseases worldwide, has challenged public health for many years. The extensive use of anticancer drugs showed severe side effects in cancer treatment [51,52,53]. Therefore, the development of an alternative and effective approach is required in the treatment of cancer. Tsao and coworkers extracted the protein (GFP) from maitake and evaluated their antitumor activity [54]. GFP is a nonglucan protein and induced the IFN-γ secretion by murine splenocytes and natural killer cells. It activated the maturation of bone-marrow-derived dendritic cells (BMDCs) via the TLR4-dependent process. A significant improvement in antitumor activity was observed in GFP-treated BMDCs when transferred into tumor-bearing mice via the activation of Th-1 response, showing the immune-modulating potential of GFP. The tumoricidal activity of maitake-extracted GFP is shown in Figure 2. BMDCs from C57BL/6J mice were cultured with tumor-antigen LLC1 lysates and treated with GFP (0.625 μg/mL) or PBS for 24 h. The LLC1-primed cells were then transferred into six-week-old C57BL/6J mice by subcutaneous injection, and a control group was injected with PBS. One week after cell transfer, LLC1 cells were inoculated into the mice at the transfer site. Ten days after LLC1 inoculation, the tumor volume was measured every other day until the end of the experiment on Day 20. All in vitro experiments were done in triplicate (n = 3), and the representative results from at least two independent works are given as the mean ± standard deviation (SD). The in vivo work was carried out in pentaplicate (n = 5).
The complex polysaccharides from mushrooms and other resources have been considered a better and effective option for antitumor activity due to their better anticancerous potential. Mushroom-derived polysaccharides can suppress tumor growth by inducing the apoptosis of tumor cells and enhancing immunotherapy and chemotherapy [55,56,57,58]. In another study, Zheng and coworkers isolated the triple-helical β-glucan (THG) from Lentinus edodes (shiitake) and examined their antitumor activity in the presence of mouse hepatoma carcinoma cell lines (H22) [59]. They fractionated the isolated THG into nine different weight-average molecular weights (Mw) by ultrasonication and established a relationship between these different fractions of THG and antitumor activity. A drastic decrease in cell viability of H22 was observed in THG-treated media compared to the control, indicating their antitumor potential. The antitumor potential of the extracted THG is profoundly affected by its molecular weight, and the low-molecular-weight fraction exhibited better antitumor activity than others. The antitumor potential of the extracted THG is also affected by its chain conformations. The low-molecular-weight fraction of THG with high chain stiffness facilitated the effective binding of β-glucan with immune cell receptors and initiated the immune responses. The structural stability and biocompatibility favor the β-glucan to use as a carrier for different nanoparticles in biomedical applications. Li et al. synthesized β-glucan-modified gold nanorods (AuNRs) and evaluated their cytotoxicity in the presence of MCF-7 cell lines [60]. Β-glucan was extracted from Pleurotus tuber-regium (king tuber) mushroom to modified AuNRs. β-glucan-coated AuNRs (AuNRs-Glu) were prepared by mixing the freshly prepared AuNRs in the aqueous glucan solution with continuous stirring at 85 °C for 30 min. A significant decrease in cell viability of MCF-7 was observed in the presence of AuNRs-Glu at 20 µg/mL and a laser power density of 0.75 W/cm2. The developed AuNRs-Glu showed greater colloidal stability in different biological media and simulated gastric fluid. The developed AuNRs-Glu demonstrated low cytotoxicity and more excellent photothermal stability, indicating an effective and suitable photothermal agent for cancer treatment. The enhancement in biocompatibility and photothermal activity was due to the wrapping of excellent biocompatible β-glucan with gold nanoparticles that significantly enhanced the colloidal and photothermal stability of the pure gold nanoparticles. The cell viability of MCF-7 cells in the presence of the synthesized AuNRs-Glu at different concentrations and power density is shown in Figure 3. Pulveroboletus ravenelii (Ravenel’s bolete) is an edible mushroom found in China, Japan, Korea, Singapore, and North America. It is commonly used in Traditional Chinese Medicine (TCM) and dye applications. Kim et al. extracted the vulpine acid (VA) from Pulveroboletus ravenelii and evaluated their anticancerous potential against various human cancer cells [61]. A substantial decrease in cell viability was observed in the presence of extracted VA, indicating its cytotoxicity against cancer cells. The cytotoxic behavior of the extracted VA against lung, pancreatic ductal, and hepatocellular carcinoma cells is shown in Figure 4. A decrease in cell viability of U937 human monocytic leukemia cells was also observed in Hericium erinaceus mushroom extract through the suppression of cell proliferation pathways [62]. The cellular responses of other mushrooms are also summarized in Table 2.

4.2. Antioxidant and Antibacterial Activity

Reactive oxygen species (ROS) have received a great amount of interest owing to their roles in several diseases such as cancer, heart disease, and diabetes [77,78,79,80,81]. Antioxidants protect the cells by the reduction of the reaction in cellular environments. Mushroom-derived polysaccharides exhibited free radical scavenging activity and can be applied as antioxidant materials for human health [82]. Liu and coworkers isolated water-soluble polysaccharides (RVLWPs) and alkaline-soluble polysaccharides (RVLAPs) from Russula vinosa and assessed their antioxidant and hepatoprotective activities on carbon tetrachloride (CCl4)-activated acute damage liver in mice [83]. RVLWP and RVLAP extracts showed remarkably better scavenging activity. Their radical scavenging activity (IC50) values in 1,1-diphenyl-2-picrylhydrazyl (DPPH) were 1.55 ± 0.004 and 3.37 ± 0.21 mg/mL for RVLWP and RVLAP, respectively. The radical scavenging activity (IC50) values in hydrogen peroxide were 6.07 ± 0.24 and 9.23 ± 0.54 mg/mL for RVLWP and RVLAP, respectively. Antioxidant activities of RVLWP and RVLAP extract are represented in Figure 5. Petrovic et al. extracted the chemical constituents from an edible Laetiporus sulphureus mushroom and studied their proximate composition, antioxidant efficiency, and antimicrobial potential [84]. The Laetiporus sulphureus derived extract exhibited better antimicrobial activity in some cases compared to the used antibiotics and mycotic. Therefore, this edible mushroom can be used as natural antioxidants or antimicrobial agents with high nutritional value and health benefits [85]. Tuberculosis (TB) is one of the severe diseases caused by Mycobacterium tuberculosis, affecting 2–3 million people per year. Isoniazid and rifampicin drugs are commonly used in the treatment of TB. However, isoniazid and rifampicin drugs demonstrated hepatotoxic activity. Therefore, it is necessary to develop more effective and alternative options from natural resources. It is well-known that Basidiomycetes mushrooms contain several bioactive compounds, including anti-TB agents. Arpha et al. isolated the chemical constituents from an edible Astraeus odoratus mushroom and evaluated their antibacterial activity, as well as cytotoxicity against H37Ra (Mycobacterium tuberculosis) and cancer cell lines, respectively [86]. Astraeus odoratus extract showed improved antibacterial and cytotoxic activity, indicating their potential to be used as an alternative supplement for antibacterial and anticancerous applications. The ion-chelation potential of the materials provides an alternative and attractive approach to remove the excess ions from body fluids. Khalili and coworkers extracted the chemical constituents from an edible Cantharellus cibarius mushroom and evaluated their iron-chelation activity in mice [87]. The extracted material exhibited the superior potential of free iron removal from the liver of mice due to their better chelation efficiency. The effects of Cantharellus cibarius extract for removing the deposited iron in the liver of mice are shown in Figure 6.

4.3. Immunomodulatory Activity

Immunomodulators play an important role in the immunity enhancement of the individual against different diseases. The individual immune system produces a variety of immunomodulatory to maintain the homeostasis of the living organism. They are categorized into immunosuppressants, immunostimulants, and immunoadjuvants [88,89,90,91]. Mushroom-derived bioactive components can stimulate both innate and adaptive immune system activities of the individual. The bioactive components proliferate and stimulate the innate immune system, such as neutrophils, natural killer (NK) cells, macrophages, and cytokine expression. The secreted cytokines trigger the adaptive immune system via the elevation of B cells for antibody generation, followed by the stimulation of T-cell differentiation to T helper (Th-1) and Th-2 cells, leading to the enhancement of the immunities. The high molecular weight of polysaccharides restricts them to direct penetration to the immune cells. Therefore, the trigger process of polysaccharides involves different cell receptors, and their efficiency is profoundly affected by their binding affinity to the receptors [88,89,90,91,92]. The immunomodulatory activities of the commonly used mushroom extract are summarized in Table 3. The different active constituents of the mushroom, such as β-glucan, protein complexes, and others, can stimulate the cellular functions to secrete the different kinds of factors for the macrophage activation, leading to the enhancement in the immunomodulatory or antitumor activities of the mushroom. Khursheed et al. also summarized the therapeutic potentials of different mushrooms [93].

5. Safety Assessment of Mushrooms

Mushrooms have gained significant popularity to be used as a dietary supplement due to different bioactive components. However, it has been seen that several medicinal mushrooms are not suitable for human health, and toxic substances occur in some medicinal mushrooms [116,117]. Therefore, it is necessary to examine the toxicological effects of mushrooms before using them as a dietary supplement. As per World Health Organization (WHO) reports, approximately 0.346 million people have died since 2004 globally, and the primary reason is mushroom poisoning [118]. Various mushroom poisoning cases are reported in different countries per year. Mushroom toxicity is categorized into seven main groups: amatoxins, orellanus, gyromitrin, muscarine, ibotenic acid, psilocybin, and coprine. Amatoxins are bicyclic octapeptides and strong toxic substances. Amatoxins inhibited the DNA-dependent RNA polymerase activity, leading to a reduction in protein synthesis, and cell necrosis or apoptosis [119]. Mushrooms having coprine cause the addiction and accumulate in the blood when consumed with alcohol. A summary of different toxic substances present in mushrooms with their potential toxicity is given in Table 4.

6. Conclusions

Mushrooms have received significant attention from the scientific community due to their high nutritional and medicinal values. They are used as a food supplement and induce the immunity of individuals through their different bioactive components. A decrease in the number of Mycobacterium tuberculosis bacteria in the presence of mushroom extract provides a new approach in the treatment of TB disease, instead of the commercially available medicines, which have cytotoxicity. A significant decrease in the cell viability of tumor cells was observed in the presence of mushroom extract, indicating their antitumor activity. Therefore, mushroom extracts have the potential to use as a food supplement for therapeutic applications.

Author Contributions

Conceptualization, methodology, D.K.P. and S.D.D.; software, S.D.D. and K.G.; validation, D.K.P., S.D.D. and K.G.; formal analysis, K.-T.L.; investigation, K.-T.L.; writing—original draft preparation, D.K.P.; writing—review and editing, S.D.D.; review and editing, S.-J.C.; visualization, supervision, project administration, funding acquisition, K.-T.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2018R1A6A1A0325582 & 2019R1D1A3A03103828), Republic of Korea. This work was also supported by the ‘Innovative Cultured Meat Technology Development-Alchemist Project’ (No. 20012439) funded by the ‘Ministry of Trade, Industry, and Energy’ (MoTIE), Republic of Korea.

Institutional Review Board Statement

This article does not contain any original research involving human or animal trials.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no competing financial interest.

References

  1. Moradali, M.-F.; Mostafavi, H.; Ghods, S.; Hedjaroude, G.-A. Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi). Int. Immunopharmacol. 2007, 7, 701–724. [Google Scholar] [CrossRef]
  2. Brown, G.D.; Herre, J.; Williams, D.L.; Willment, J.A.; Marshall, A.S.J.; Gordon, S. Dectin-1 Mediates the Biological Effects of β-Glucans. J. Exp. Med. 2003, 197, 1119–1124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Vetvicka, V.; Vashishta, A.; Saraswat-Ohri, S.; Vetvickova, J. Immunological Effects of Yeast- and Mushroom-Derived β-Glucans. J. Med. Food 2008, 11, 615–622. [Google Scholar] [CrossRef]
  4. Wasser, S. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl. Microbiol. Biotechnol. 2002, 60, 258–274. [Google Scholar] [PubMed]
  5. Wu, M.-J.; Cheng, T.-L.; Cheng, S.-Y.; Lian, T.-W.; Wang, L.; Chiou, S.-Y. Immunomodulatory Properties ofGrifola frondosain Submerged Culture. J. Agric. Food Chem. 2006, 54, 2906–2914. [Google Scholar] [CrossRef] [PubMed]
  6. Guillamón, E.; García-Lafuente, A.; Lozano, M.; D’Arrigo, M.; Rostagno, M.A.; Villares, A.; Martinez, J.A. Edible mushrooms: Role in the prevention of cardiovascular diseases. Fitoterapia 2010, 81, 715–723. [Google Scholar] [CrossRef] [PubMed]
  7. Heleno, S.A.; Barros, L.; Sousa, M.J.; Martins, A.; Ferreira, I.C.F.R. Tocopherols composition of Portuguese wild mushrooms with antioxidant capacity. Food Chem. 2010, 119, 1443–1450. [Google Scholar] [CrossRef] [Green Version]
  8. Mattila, P.; Könkö, K.; Eurola, M.; Pihlava, J.-M.; Astola, J.; Vahteristo, L.; Hietaniemi, V.; Kumpulainen, J.; Valtonen, M.; Piironen, V. Contents of Vitamins, Mineral Elements, and Some Phenolic Compounds in Cultivated Mushrooms. J. Agric. Food Chem. 2001, 49, 2343–2348. [Google Scholar] [CrossRef]
  9. Kohler, J.R.; Casadevall, A.; Perfect, J. The Spectrum of Fungi That Infects Humans. Cold Spring Harb. Perspect. Med. 2014, 5, a019273. [Google Scholar] [CrossRef] [Green Version]
  10. Huang, X.; Nie, S. The structure of mushroom polysaccharides and their beneficial role in health. Food Funct. 2015, 6, 3205–3217. [Google Scholar] [CrossRef]
  11. Pelley, R.P.; Strickland, F.M. Plants, Polysaccharides, and the Treatment and Prevention of Neoplasia. Crit. Rev. Oncog. 2000, 11, 38. [Google Scholar] [CrossRef]
  12. Baldassano, S.; Accardi, G.; Vasto, S. Beta-glucans and cancer: The influence of inflammation and gut peptide. Eur. J. Med. Chem. 2017, 142, 486–492. [Google Scholar] [CrossRef] [PubMed]
  13. Chen, S.-N.; Chang, C.-S.; Hung, M.-H.; Chen, S.; Wang, W.; Tai, C.-J.; Lu, C.-L. The Effect of Mushroom Beta-Glucans from Solid Culture of Ganoderma lucidumon Inhibition of the Primary Tumor Metastasis. Evid. Based Complement. Altern. Med. 2014, 2014, 1–7. [Google Scholar]
  14. Ayeka, P.A. Potential of Mushroom Compounds as Immunomodulators in Cancer Immunotherapy: A Review. Evid. Based Complement. Altern. Med. 2018, 2018, 1–9. [Google Scholar] [CrossRef]
  15. Guggenheim, A.G.; Wright, K.M.; Zwickey, H.L. Immune modulation from five major mushrooms: Application to integrative oncology. Integr. Med. A Clin. J. 2014, 13, 32. [Google Scholar]
  16. Wang, Y.; Fang, J.; Ni, X.; Li, J.; Liu, Q.; Dong, Q.; Duan, J.; Ding, K. Inducement of Cytokine Release by GFPBW2, a Novel Polysaccharide from Fruit Bodies of Grifola frondosa, through Dectin-1 in Macrophages. J. Agric. Food Chem. 2013, 61, 11400–11409. [Google Scholar] [CrossRef]
  17. Novak, M.; Vetvicka, V. β-Glucans, History, and the Present: Immunomodulatory Aspects and Mechanisms of Action. J. Immunotoxicol. 2008, 5, 47–57. [Google Scholar] [CrossRef]
  18. Novak, M.; Vetvicka, V. Glucans as Biological Response Modifiers. Endocr. Metab. Immune Disord. Drug Targets 2009, 9, 67–75. [Google Scholar] [CrossRef]
  19. Vetvicka, V.; Vetvickova, J. Immune enhancing effects of WB365: A novel combination of Ashwagandha (Withania somnifera) and Maitake (Grifola frondosa) extracts. N. Am. J. Med. Sci. 2011, 3, 320–324. [Google Scholar] [CrossRef]
  20. Rahar, S.; Swami, G.; Nagpal, N.; Nagpal, M.; Singh, G. Preparation, characterization, and biological properties of β-glucans. J. Adv. Pharm. Technol. Res. 2011, 2, 94. [Google Scholar] [CrossRef]
  21. Lavi, I.; Levinson, D.; Peri, I.; Nimri, L.; Hadar, Y.; Schwartz, B. Orally administered glucans from the edible mushroomPleurotus pulmonariusreduce acute inflammation in dextran sulfate sodium-induced experimental colitis. Br. J. Nutr. 2009, 103, 393–402. [Google Scholar] [CrossRef] [Green Version]
  22. Wong, K.-H.; Lai, C.K.M.; Cheung, P.C.K. Immunomodulatory activities of mushroom sclerotial polysaccharides. Food Hydrocoll. 2011, 25, 150–158. [Google Scholar] [CrossRef]
  23. Scheller, J.; Chalaris, A.; Schmidt-Arras, D.; Rose-John, S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta (BBA) Mol. Cell Res. 2011, 1813, 878–888. [Google Scholar] [CrossRef] [Green Version]
  24. Su, D.-L.; Lu, Z.-M.; Shen, M.-N.; Li, X.; Sun, L.-Y. Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE. J. Biomed. Biotechnol. 2012, 2012, 1–15. [Google Scholar] [CrossRef]
  25. Wojdasiewicz, P.; Poniatowski, Ł.A.; Szukiewicz, D. The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis. Mediat. Inflamm. 2014, 2014, 1–19. [Google Scholar] [CrossRef] [Green Version]
  26. Adachi, Y.; Okazaki, M.; Ohno, N.; Yadomae, T. Enhancement of Cytokine Production by Macrophages Stimulated with (1→3)-β-BETA-d-Glucan, Grifolan (GRN), Isolated from Grifola frondosa. Biol. Pharm. Bull. 1994, 17, 1554–1560. [Google Scholar] [CrossRef] [Green Version]
  27. Okazaki, M.; Adachi, Y.; Ohno, N.; Yadomae, T. Structure-Activity Relationship of (1.RAR.3)-.BETA.-d-Glucans in the Induction of Cytokine Production from Macrophages, in Vitro. Biol. Pharm. Bull. 1995, 18, 1320–1327. [Google Scholar] [CrossRef] [Green Version]
  28. Zhang, M.; Cheung, P.C.K.; Zhang, L. Evaluation of Mushroom Dietary Fiber (Nonstarch Polysaccharides) from Sclerotia of Pleurotus tuber-regium(Fries) Singer as a Potential Antitumor Agent. J. Agric. Food Chem. 2001, 49, 5059–5062. [Google Scholar] [CrossRef]
  29. Nworu, C.S.; Ihim, S.A.; Okoye, F.B.C.; Esimone, C.O.; Adikwu, M.U.; Akah, P.A. Immunomodulatory and immunorestorative activities of β-d-glucan-rich extract and polysaccharide fraction of mushroom, Pleurutus tuberregium. Pharm. Biol. 2015, 53, 1555–1566. [Google Scholar] [CrossRef]
  30. Lull, C.; Wichers, H.J.; Savelkoul, H.F.J. Antiinflammatory and Immunomodulating Properties of Fungal Metabolites. Mediat. Inflamm. 2005, 2005, 63–80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  31. Borchers, A.T.; Krishnamurthy, A.; Keen, C.L.; Meyers, F.J.; Gershwin, M.E. The Immunobiology of Mushrooms. Exp. Biol. Med. 2008, 233, 259–276. [Google Scholar] [CrossRef]
  32. Ramsaha, S.; Neergheen-Bhujun, V.S.; Verma, S.; Kumar, A.; Bharty, R.K.; Chaudhary, A.K.; Sharma, P.; Singh, R.K.; Beejan, P.H.F.; Kang, K.-S.; et al. Modulation of hepatocarcinogenesis in N-methyl-N-nitrosourea treated Balb/c mice by mushroom extracts. Food Funct. 2016, 7, 594–609. [Google Scholar] [CrossRef]
  33. Ma, X.; Meng, M.; Han, L.; Cheng, D.; Cao, X.; Wang, C. Structural characterization and immunomodulatory activity of Grifola frondosa polysaccharide via toll-like receptor 4–mitogen-activated protein kinases–nuclear factor κB pathways. Food Funct. 2016, 7, 2763–2772. [Google Scholar] [CrossRef]
  34. Su, C.-H.; Lai, M.-N.; Ng, L.-T. Inhibitory effects of medicinal mushrooms on α-amylase and α-glucosidase—enzymes related to hyperglycemia. Food Funct. 2013, 4, 644. [Google Scholar] [CrossRef] [PubMed]
  35. Ligor, M.; Ratiu, I.-A.; Kiełbasa, A.; Al-Suod, H.; Buszewski, B. Extraction approaches used for the determination of biologically active compounds (cyclitols, polyphenols and saponins) isolated from plant material. Electrophoresis 2018, 39, 1860–1874. [Google Scholar] [CrossRef]
  36. Ratiu, I.-A.; Al-Suod, H.; Ligor, M.; Ligor, T.; Railean-Plugaru, V.; Buszewski, B. Complex investigation of extraction techniques applied for cyclitols and sugars isolation from different species ofSolidagogenus. Electrophoresis 2018, 39, 1966–1974. [Google Scholar] [CrossRef]
  37. Wang, L.; Weller, C.L. Recent advances in extraction of nutraceuticals from plants. Trends Food Sci. Technol. 2006, 17, 300–312. [Google Scholar] [CrossRef]
  38. Volman, J.J.; Helsper, J.P.F.G.; Wei, S.; Baars, J.J.P.; van Griensven, L.J.L.D.; Sonnenberg, A.S.M.; Mensink, R.P.; Plat, J. Effects of mushroom-derived β-glucan-rich polysaccharide extracts on nitric oxide production by bone marrow-derived macrophages and nuclear factor-κB transactivation in Caco-2 reporter cells: Can effects be explained by structure? Mol. Nutr. Food Res. 2010, 54, 268–276. [Google Scholar] [CrossRef] [PubMed]
  39. Kothari, D.; Patel, S.; Kim, S.-K. Anticancer and other therapeutic relevance of mushroom polysaccharides: A holistic appraisal. Biomed. Pharmacother. 2018, 105, 377–394. [Google Scholar] [CrossRef]
  40. Shashidhar, G.M.; Giridhar, P.; Manohar, B. Functional polysaccharides from medicinal mushroom Cordyceps sinensis as a potent food supplement: Extraction, characterization and therapeutic potentials—A systematic review. RSC Adv. 2015, 5, 16050–16066. [Google Scholar] [CrossRef]
  41. Yoshida, I.; Kiho, T.; Usui, S.; Sakushima, M.; Ukai, S. Polysaccharides in Fungi. XXXVII. Immunomodulating Activities of Carboxymethylated Derivatives of Linear (1→3)-α-d-Glucans Extracted from the Fruiting Bodies of Agrocybe cylindracea and Amanita muscaria. Biol. Pharm. Bull. 1996, 19, 114–121. [Google Scholar] [CrossRef] [Green Version]
  42. Wang, Z.-M.; Peng, X.; Lee, K.-L.D.; Tang, J.C.-O.; Cheung, P.C.-K.; Wu, J.-Y. Structural characterisation and immunomodulatory property of an acidic polysaccharide from mycelial culture of Cordyceps sinensis fungus Cs-HK1. Food Chem. 2011, 125, 637–643. [Google Scholar] [CrossRef]
  43. Vetvicka, V.; Vetvickova, J. Immune-enhancing effects of maitake (Grifola frondosa) and shiitake (Lentinula edodes) extracts. Ann. Transl. Med. 2014, 2, 14–20. [Google Scholar]
  44. Petrovska, B. Historical review of medicinal plants′ usage. Pharmacogn. Rev. 2012, 6, 1. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Al-Suod, H.; Ratiu, I.A.; Krakowska-Sieprawska, A.; Lahuta, L.; Górecki, R.; Buszewski, B. Supercritical fluid extraction in isolation of cyclitols and sugars from chamomile flowers. J. Sep. Sci. 2019, 42, 3243–3252. [Google Scholar] [CrossRef] [PubMed]
  46. Ak, M. A Brief Review of Traditional plants as Sources of Pharmacological interests. Open J. Plant Sci. 2019, 4, 1–8. [Google Scholar] [CrossRef] [Green Version]
  47. Ullah, R.; Alqahtani, A.S.; Noman, O.M.A.; Alqahtani, A.M.; Ibenmoussa, S.; Bourhia, M. A review on ethno-medicinal plants used in traditional medicine in the Kingdom of Saudi Arabia. Saudi J. Biol. Sci. 2020, 27, 2706–2718. [Google Scholar] [CrossRef]
  48. Ratiu, I.A.; Al-Suod, H.; Ligor, M.; Ligor, T.; Krakowska, A.; Górecki, R.; Buszewski, B. Simultaneous Determination of Cyclitols and Sugars Following a Comprehensive Investigation of 40 Plants. Food Anal. Methods 2019, 12, 1466–1478. [Google Scholar] [CrossRef] [Green Version]
  49. Kodama, N.; Harada, N.; Nanba, H. A Polysaccharide, Extract from Grifola frondosa, Induces Th-1 Dominant Responses in Carcinoma-Bearing BALB/c Mice. Jpn. J. Pharmacol. 2002, 90, 357–360. [Google Scholar] [CrossRef] [Green Version]
  50. Harada, N.; Kodama, N.; Nanba, H. Relationship between dendritic cells and the D-fraction-induced Th-1 dominant response in BALB/c tumor-bearing mice. Cancer Lett. 2003, 192, 181–187. [Google Scholar] [CrossRef]
  51. Miltenburg, N.C.; Boogerd, W. Chemotherapy-induced neuropathy: A comprehensive survey. Cancer Treat. Rev. 2014, 40, 872–882. [Google Scholar] [CrossRef]
  52. Yi, Q.; Ma, J.; Kang, K.; Gu, Z. Dual cellular stimuli-responsive hydrogel nanocapsules for delivery of anticancer drugs. J. Mater. Chem. B 2016, 4, 4922–4933. [Google Scholar] [CrossRef]
  53. Shakeri-Zadeh, A.; Khoee, S.; Shiran, M.-B.; Sharifi, A.M.; Khoei, S. Synergistic effects of magnetic drug targeting using a newly developed nanocapsule and tumor irradiation by ultrasound on CT26 tumors in BALB/c mice. J. Mater. Chem. B 2015, 3, 1879–1887. [Google Scholar] [CrossRef]
  54. Tsao, Y.-W.; Kuan, Y.-C.; Wang, J.-L.; Sheu, F. Characterization of a Novel Maitake (Grifola frondosa) Protein That Activates Natural Killer and Dendritic Cells and Enhances Antitumor Immunity in Mice. J. Agric. Food Chem. 2013, 61, 9828–9838. [Google Scholar] [CrossRef] [PubMed]
  55. Wu, B.; Cui, J.; Zhang, C.; Li, Z. A polysaccharide from Agaricus blazei inhibits proliferation and promotes apoptosis of osteosarcoma cells. Int. J. Biol. Macromol. 2012, 50, 1116–1120. [Google Scholar] [CrossRef] [PubMed]
  56. Bae, J.-S.; Jang, K.-H.; Jin, H.K. Effects of natural polysaccharides on the growth and peritoneal carcinomatosis of human gastric adenocarcinoma in a nude mouse model. Cancer Lett. 2006, 235, 60–68. [Google Scholar] [CrossRef]
  57. Lu, H.; Yang, Y.; Gad, E.; Wenner, C.A.; Chang, A.; Larson, E.R.; Dang, Y.; Martzen, M.; Standish, L.J.; Disis, M.L. Polysaccharide Krestin Is a Novel TLR2 Agonist that Mediates Inhibition of Tumor Growth via Stimulation of CD8 T Cells and NK Cells. Clin. Cancer Res. 2011, 17, 67–76. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  58. Hong, F.; Yan, J.; Baran, J.T.; Allendorf, D.J.; Hansen, R.D.; Ostroff, G.R.; Xing, P.X.; Cheung, N.K.V.; Ross, G.D. Mechanism by Which Orally Administered β-1, 3-Glucans Enhance the Tumoricidal Activity of Antitumor Monoclonal Antibodies in Murine Tumor Models. J. Immunol. 2004, 173, 797–806. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  59. Zheng, X.; Lu, F.; Xu, X.; Zhang, L. Extended chain conformation of β-glucan and its effect on antitumor activity. J. Mater. Chem. B 2017, 5, 5623–5631. [Google Scholar] [CrossRef]
  60. Li, X.; Zhou, J.; Liu, C.; Xiong, Q.; Duan, H.; Cheung, P.C.K. Stable and Biocompatible Mushroom β-Glucan Modified Gold Nanorods for Cancer Photothermal Therapy. J. Agric. Food Chem. 2017, 65, 9529–9536. [Google Scholar] [CrossRef] [PubMed]
  61. Kim, S.; So, H.M.; Roh, H.-S.; Kim, J.; Yu, J.S.; Lee, S.; Seok, S.; Pang, C.; Baek, K.H.; Kim, K.H. Vulpinic acid contributes to the cytotoxicity of Pulveroboletus ravenelii to human cancer cells by inducing apoptosis. RSC Adv. 2017, 7, 35297–35304. [Google Scholar] [CrossRef] [Green Version]
  62. Kim, S.P.; Kang, M.Y.; Choi, Y.H.; Kim, J.H.; Nam, S.H.; Friedman, M. Mechanism of Hericium erinaceus (Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cells. Food Funct. 2011, 2, 348. [Google Scholar] [CrossRef]
  63. Takimoto, H.; Kato, H.; Kaneko, M.; Kumazawa, Y. Amelioration of Skewed Th1/Th2 Balance in Tumor-Bearing and Asthma-Induced Mice by Oral Administration ofAgaricus blazeiExtracts. Immunopharmacol. Immunotoxicol. 2008, 30, 747–760. [Google Scholar] [CrossRef]
  64. Lin, J.-G.; Fan, M.-J.; Tang, N.-Y.; Yang, J.-S.; Hsia, T.-C.; Lin, J.-J.; Lai, K.-C.; Wu, R.S.C.; Ma, C.Y.; Wood, W.G.; et al. An Extract of Agaricus blazei Murill Administered Orally Promotes Immune Responses in Murine Leukemia BALB/c Mice In Vivo. Integr. Cancer Ther. 2012, 11, 29–36. [Google Scholar] [CrossRef] [Green Version]
  65. Lin, H.; She, Y.-H.; Cassileth, B.R.; Sirotnak, F.; Cunningham Rundles, S. Maitake beta-glucan MD-fraction enhances bone marrow colony formation and reduces doxorubicin toxicity in vitro. Int. Immunopharmacol. 2004, 4, 91–99. [Google Scholar] [CrossRef]
  66. Gao, Y.; Zhou, S.; Jiang, W.; Huang, M.; Dai, X. Effects of Ganopoly®(AGanoderma lucidumPolysaccharide Extract) on the Immune Functions in Advanced-Stage Cancer Patients. Immunol. Investig. 2009, 32, 201–215. [Google Scholar] [CrossRef] [PubMed]
  67. Zhang, S.; Nie, S.; Huang, D.; Huang, J.; Feng, Y.; Xie, M. A Polysaccharide from Ganoderma atrum Inhibits Tumor Growth by Induction of Apoptosis and Activation of Immune Response in CT26-Bearing Mice. J. Agric. Food Chem. 2014, 62, 9296–9304. [Google Scholar] [CrossRef] [PubMed]
  68. Wang, G.; Zhao, J.; Liu, J.; Huang, Y.; Zhong, J.-J.; Tang, W. Enhancement of IL-2 and IFN-γ expression and NK cells activity involved in the anti-tumor effect of ganoderic acid Me in vivo. Int. Immunopharmacol. 2007, 7, 864–870. [Google Scholar] [CrossRef] [PubMed]
  69. Lee, E.-J.; Kim, W.-J.; Moon, S.-K. Cordycepin suppresses TNF-alpha-induced invasion, migration and matrix metalloproteinase-9 expression in human bladder cancer cells. Phytother. Res. 2010, 24, 1755–1761. [Google Scholar] [CrossRef] [PubMed]
  70. Torkelson, C.J.; Sweet, E.; Martzen, M.R.; Sasagawa, M.; Wenner, C.A.; Gay, J.; Putiri, A.; Standish, L.J. Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer. ISRN Oncol. 2012, 2012, 1–7. [Google Scholar] [CrossRef] [Green Version]
  71. Lee, S.H.; Lillehoj, H.S.; Hong, Y.H.; Jang, S.I.; Lillehoj, E.P.; Ionescu, C.; Mazurnok, L.; Bravo, D. In vitroeffects of plant and mushroom extracts on immunological function of chicken lymphocytes and macrophages. Br. Poult. Sci. 2010, 51, 213–221. [Google Scholar] [CrossRef] [PubMed]
  72. Ajith, T.A.; Janardhanan, K.K. Cytotoxic and antitumor activities of a polypore macrofungus, Phellinus rimosus (Berk) Pilat. J. Ethnopharmacol. 2003, 84, 157–162. [Google Scholar] [CrossRef]
  73. Lee, Y.S.; Kim, Y.H.; Shin, E.K.; Kim, D.H.; Lim, S.S.; Lee, J.-Y.; Kim, J.-K. Anti-angiogenic activity of methanol extract of Phellinus linteus and its fractions. J. Ethnopharmacol. 2010, 131, 56–62. [Google Scholar] [CrossRef] [PubMed]
  74. Jose, N.; Ajith, T.A.; Janardhanan, K.K. Methanol extract of the oyster mushroom, Pleurotus florida, inhibits inflammation and platelet aggregation. Phytother. Res. 2004, 18, 43–46. [Google Scholar] [CrossRef]
  75. Ye, M.; Luo, X.; Li, L.; Shi, Y.; Tan, M.; Weng, X.; Li, W.; Liu, J.; Cao, Y. Grifolin, a potential antitumor natural product from the mushroom Albatrellus confluens, induces cell-cycle arrest in G1 phase via the ERK1/2 pathway. Cancer Lett. 2007, 258, 199–207. [Google Scholar] [CrossRef]
  76. Luo, X.-J.; Li, L.-L.; Deng, Q.-P.; Yu, X.-F.; Yang, L.-F.; Luo, F.-J.; Xiao, L.; Chen, X.-Y.; Ye, M.; Liu, J.-K.; et al. Grifolin, a potent antitumour natural product upregulates death-associated protein kinase 1 DAPK1 via p53 in nasopharyngeal carcinoma cells. Eur. J. Cancer 2011, 47, 316–325. [Google Scholar] [CrossRef]
  77. Ganie, S.A.; Haq, E.; Masood, A.; Hamid, A.; Zargar, M.A. Antioxidant and Protective Effect of Ethyl Acetate Extract of Podophyllum hexandrumRhizome on Carbon Tetrachloride Induced Rat Liver Injury. Evid. Based Complement. Altern. Med. 2011, 2011, 1–12. [Google Scholar] [CrossRef] [Green Version]
  78. Panth, N.; Paudel, K.R.; Parajuli, K. Reactive Oxygen Species: A Key Hallmark of Cardiovascular Disease. Adv. Med. 2016, 2016, 1–12. [Google Scholar] [CrossRef] [Green Version]
  79. Siasos, G.; Tsigkou, V.; Kosmopoulos, M.; Theodosiadis, D.; Simantiris, S.; Tagkou, N.M.; Tsimpiktsioglou, A.; Stampouloglou, P.K.; Oikonomou, E.; Mourouzis, K.; et al. Mitochondria and cardiovascular diseases—From pathophysiology to treatment. Ann. Transl. Med. 2018, 6, 256. [Google Scholar] [CrossRef] [PubMed]
  80. Ratiu, I.A.; Ligor, T.; Bocos-Bintintan, V.; Mayhew, C.A.; Buszewski, B. Volatile Organic Compounds in Exhaled Breath as Fingerprints of Lung Cancer, Asthma and COPD. J. Clin. Med. 2020, 10, 32. [Google Scholar] [CrossRef]
  81. Nishikawa, T.; Araki, E. Impact of Mitochondrial ROS Production in the Pathogenesis of Diabetes Mellitus and Its Complications. Antioxid. Redox Signal. 2007, 9, 343–353. [Google Scholar] [CrossRef]
  82. Soares, A.; de Sá-Nakanishi, A.; Bracht, A.; da Costa, S.; Koehnlein, E.; de Souza, C.; Peralta, R.M. Hepatoprotective Effects of Mushrooms. Molecules 2013, 18, 7609–7630. [Google Scholar] [CrossRef] [Green Version]
  83. Liu, Q.; Tian, G.; Yan, H.; Geng, X.; Cao, Q.; Wang, H.; Ng, T.B. Characterization of Polysaccharides with Antioxidant and Hepatoprotective Activities from the Wild Edible Mushroom Russula vinosa Lindblad. J. Agric. Food Chem. 2014, 62, 8858–8866. [Google Scholar] [CrossRef] [PubMed]
  84. Petrović, J.; Papandreou, M.; Glamočlija, J.; Ćirić, A.; Baskakis, C.; Proestos, C.; Lamari, F.; Zoumpoulakis, P.; Sokovic, M. Different extraction methodologies and their influence on the bioactivity of the wild edible mushroom Laetiporus sulphureus (Bull.) Murrill. Food Funct. 2014, 5, 2948–2960. [Google Scholar]
  85. García, A.; Bocanegra-García, V.; Palma-Nicolás, J.P.; Rivera, G. Recent advances in antitubercular natural products. Eur. J. Med. Chem. 2012, 49, 1–23. [Google Scholar] [CrossRef]
  86. Arpha, K.; Phosri, C.; Suwannasai, N.; Mongkolthanaruk, W.; Sodngam, S. Astraodoric Acids A–D: New Lanostane Triterpenes from Edible Mushroom Astraeus odoratus and Their Anti-Mycobacterium tuberculosis H37Ra and Cytotoxic Activity. J. Agric. Food Chem. 2012, 60, 9834–9841. [Google Scholar] [CrossRef] [PubMed]
  87. Khalili, M.; Ebrahimzadeh, M.A.; Kosaryan, M.; Abbasi, A.; Azadbakht, M. Iron chelation and liver disease healing activity of edible mushroom (Cantharellus cibarius), in vitro and in vivo assays. RSC Adv. 2015, 5, 4804–4810. [Google Scholar] [CrossRef]
  88. Chen, J.; Seviour, R. Medicinal importance of fungal β-(1 → 3), (1 → 6)-glucans. Mycol. Res. 2007, 111, 635–652. [Google Scholar] [CrossRef] [PubMed]
  89. Suthanthiran, M.; Morris, R.E.; Strom, T.B. Immunosuppressants: Cellular and molecular mechanisms of action. Am. J. Kidney Dis. 1996, 28, 159–172. [Google Scholar] [CrossRef]
  90. Puggioni, F.; Alves-Correia, M.; Mohamed, M.-F.; Stomeo, N.; Mager, R.; Marinoni, M.; Racca, F.; Paoletti, G.; Varricchi, G.; Giorgis, V.; et al. Immunostimulants in respiratory diseases: Focus on Pidotimod. Multidiscip. Respir. Med. 2019, 14, 31. [Google Scholar] [CrossRef] [Green Version]
  91. Banstola, A.; Jeong, J.-H.; Yook, S. Immunoadjuvants for cancer immunotherapy: A review of recent developments. Acta Biomater. 2020, 114, 16–30. [Google Scholar] [CrossRef] [PubMed]
  92. El Enshasy, H.A.; Hatti-Kaul, R. Mushroom immunomodulators, unique molecules with unlimited applications. Trends Biotechnol. 2013, 31, 668–677. [Google Scholar] [CrossRef] [PubMed]
  93. Ditamo, Y.; Rupil, L.L.; Sendra, V.G.; Nores, G.A.; Roth, G.A.; Irazoqui, F.J. In vivo immunomodulatory effect of the lectin from edible mushroom Agaricus bisporus. Food Funct. 2016, 7, 262–269. [Google Scholar] [CrossRef]
  94. Cheng, F.; Yan, X.; Zhang, M.; Chang, M.; Yun, S.; Meng, J.; Liu, J.; Feng, C.-P. Regulation of RAW 264.7 cell-mediated immunity by polysaccharides from Agaricus blazei Murill via the MAPK signal transduction pathway. Food Funct. 2017, 8, 1475–1480. [Google Scholar] [CrossRef]
  95. Suabjakyong, P.; Nishimura, K.; Toida, T.; Van Griensven, L.J.L.D. Structural characterization and immunomodulatory effects of polysaccharides from Phellinus linteus and Phellinus igniarius on the IL-6/IL-10 cytokine balance of the mouse macrophage cell lines (RAW 264.7). Food Funct. 2015, 6, 2834–2844. [Google Scholar] [CrossRef] [Green Version]
  96. Ma, X.-K.; Ma, Y.; Peterson, E.C.; Guo, W.Y.; Li, Z.Y.; Li, Y. Structural characterization of two endopolysaccharides from Phellinus sp. and their immunologic effects by intragastric administration in a healthy mammalian model. Food Funct. 2018, 9, 1224–1234. [Google Scholar] [CrossRef]
  97. Ma, X.-K.; Guo, D.D.; Peterson, E.C.; Dun, Y.; Li, D.Y. Structural characterization and anti-aging activity of a novel extracellular polysaccharide from fungus Phellinus sp. in a mammalian system. Food Funct. 2016, 7, 3468–3479. [Google Scholar] [CrossRef]
  98. Du, J.; Li, J.; Zhu, J.; Huang, C.; Bi, S.; Song, L.; Hu, X.; Yu, R. Structural characterization and immunomodulatory activity of a novel polysaccharide from Ficus carica. Food Funct. 2018, 9, 3930–3943. [Google Scholar] [CrossRef] [PubMed]
  99. Hu, Q.; Du, H.; Ma, G.; Pei, F.; Ma, N.; Yuan, B.; Nakata, P.A.; Yang, W. Purification, identification and functional characterization of an immunomodulatory protein from Pleurotus eryngii. Food Funct. 2018, 9, 3764–3775. [Google Scholar] [CrossRef]
  100. Wu, G.-H.; Lu, C.-L.; Jiang, J.-G.; Li, Z.-Y.; Huang, Z.-L. Regulation effect of polysaccharides from Pleurotus tuber-regium (Fr.) on the immune activity of mice macrophages. Food Funct. 2014, 5, 337–344. [Google Scholar] [CrossRef]
  101. Yuan, B.; Zhao, L.; Rakariyatham, K.; Han, Y.; Gao, Z.; Muinde Kimatu, B.; Hu, Q.; Xiao, H. Isolation of a novel bioactive protein from an edible mushroom Pleurotus eryngii and its anti-inflammatory potential. Food Funct. 2017, 8, 2175–2183. [Google Scholar] [CrossRef] [PubMed]
  102. Hu, Q.; Yuan, B.; Xiao, H.; Zhao, L.; Wu, X.; Rakariyatham, K.; Zhong, L.; Han, Y.; Kimatu, B.M.; Yang, W. Polyphenols-rich extract from Pleurotus eryngii with growth inhibitory of HCT116 colon cancer cells and anti-inflammatory function in RAW264.7 cells. Food Funct. 2018, 9, 1601–1611. [Google Scholar] [CrossRef] [PubMed]
  103. Chen, J.-N.; Ma, C.-Y.; Tsai, P.-F.; Wang, Y.-T.; Wu, J.S.-B. In Vitro Antitumor and Immunomodulatory Effects of the Protein PCP-3A from MushroomPleurotus citrinopileatus. J. Agric. Food Chem. 2010, 58, 12117–12122. [Google Scholar] [CrossRef]
  104. Chen, J.-N.; Wang, Y.-T.; Wu, J.S.-B. A Glycoprotein Extracted from Golden Oyster Mushroom Pleurotus citrinopileatus Exhibiting Growth Inhibitory Effect against U937 Leukemia Cells. J. Agric. Food Chem. 2009, 57, 6706–6711. [Google Scholar] [CrossRef]
  105. Chen, J.-N.; de Mejia, E.G.; Wu, J.S.-B. Inhibitory Effect of a Glycoprotein Isolated from Golden Oyster Mushroom (Pleurotus citrinopileatus) on the Lipopolysaccharide-Induced Inflammatory Reaction in RAW 264.7 Macrophage. J. Agric. Food Chem. 2011, 59, 7092–7097. [Google Scholar] [CrossRef] [PubMed]
  106. Li, C.; You, L.; Fu, X.; Huang, Q.; Yu, S.; Liu, R.H. Structural characterization and immunomodulatory activity of a new heteropolysaccharide from Prunella vulgaris. Food Funct. 2015, 6, 1557–1567. [Google Scholar] [CrossRef]
  107. Xu, X.; Yang, J.; Luo, Z.; Zhang, X. Lentinula edodes-derived polysaccharide enhances systemic and mucosal immunity by spatial modulation of intestinal gene expression in mice. Food Funct. 2015, 6, 2068–2080. [Google Scholar] [CrossRef]
  108. Wang, L.; Nie, Z.-K.; Zhou, Q.; Zhang, J.-L.; Yin, J.-J.; Xu, W.; Qiu, Y.; Ming, Y.-L.; Liang, S. Antitumor efficacy in H22 tumor bearing mice and immunoregulatory activity on RAW 264.7 macrophages of polysaccharides from Talinum triangulare. Food Funct. 2014, 5, 2183. [Google Scholar] [CrossRef]
  109. Lee, J.; Ha, S.J.; Lee, H.J.; Kim, M.J.; Kim, J.H.; Kim, Y.T.; Song, K.-M.; Kim, Y.-J.; Kim, H.K.; Jung, S.K. Protective effect of Tremella fuciformis Berk extract on LPS-induced acute inflammation via inhibition of the NF-κB and MAPK pathways. Food Funct. 2016, 7, 3263–3272. [Google Scholar] [CrossRef]
  110. Sheu, F.; Chien, P.-J.; Hsieh, K.-Y.; Chin, K.-L.; Huang, W.-T.; Tsao, C.-Y.; Chen, Y.F.; Cheng, H.C.; Chang, H.H. Purification, Cloning, and Functional Characterization of a Novel Immunomodulatory Protein from Antrodia camphorata (Bitter Mushroom) That Exhibits TLR2-Dependent NF-κB Activation and M1 Polarization within Murine Macrophages. J. Agric. Food Chem. 2009, 57, 4130–4141. [Google Scholar] [CrossRef]
  111. Chang, H.-H.; Yeh, C.-H.; Sheu, F. A Novel Immunomodulatory Protein from Poria cocos Induces Toll-like Receptor 4-Dependent Activation within Mouse Peritoneal Macrophages. J. Agric. Food Chem. 2009, 57, 6129–6139. [Google Scholar] [CrossRef]
  112. Xu, H.; Kong, Y.-Y.; Chen, X.; Guo, M.-Y.; Bai, X.-H.; Lu, Y.-J.; Li, W.; Zhou, X.W. Recombinant FIP-gat: A Fungal Immunomodulatory Protein from Ganoderma atrum, Induces Growth Inhibition and Cell Death in Breast Cancer Cells. J. Agric. Food Chem. 2016, 64, 2690–2698. [Google Scholar]
  113. Hoshi, H.; Yagi, Y.; Iijima, H.; Matsunaga, K.; Ishihara, Y.; Yasuhara, T. Isolation and Characterization of a Novel Immunomodulatory α-Glucan−Protein Complex from the Mycelium of Tricholoma matsutakein Basidiomycetes. J. Agric. Food Chem. 2005, 53, 8948–8956. [Google Scholar] [CrossRef]
  114. Kim, S.P.; Moon, E.; Nam, S.H.; Friedman, M. Hericium erinaceus Mushroom Extracts Protect Infected Mice against Salmonella Typhimurium-Induced Liver Damage and Mortality by Stimulation of Innate Immune Cells. J. Agric. Food Chem. 2012, 60, 5590–5596. [Google Scholar] [CrossRef] [PubMed]
  115. Chang, Y.-C.; Hsiao, Y.-M.; Wu, M.-F.; Ou, C.-C.; Lin, Y.-W.; Lue, K.-H.; Ko, J.-L. Interruption of Lung Cancer Cell Migration and Proliferation by Fungal Immunomodulatory Protein FIP-fve from Flammulina velutipes. J. Agric. Food Chem. 2013, 61, 12044–12052. [Google Scholar] [CrossRef] [PubMed]
  116. Khursheed, R.; Singh, S.K.; Wadhwa, S.; Gulati, M.; Awasthi, A. Therapeutic potential of mushrooms in diabetes mellitus: Role of polysaccharides. Int. J. Biol. Macromol. 2020, 164, 1194–1205. [Google Scholar] [CrossRef] [PubMed]
  117. VanderMolen, K.M.; Little, J.G.; Sica, V.P.; El-Elimat, T.; Raja, H.A.; Oberlies, N.H.; Baker, T.R.; Mahoy, C. Safety assessment of mushrooms in dietary supplements by combining analytical data with in silico toxicology evaluation. Food Chem. Toxicol. 2017, 103, 133–147. [Google Scholar] [CrossRef]
  118. Jo, W.-S.; Hossain, M.A.; Park, S.-C. Toxicological Profiles of Poisonous, Edible, and Medicinal Mushrooms. Mycobiology 2018, 42, 215–220. [Google Scholar] [CrossRef] [Green Version]
  119. Wieland, T.; GÖTzendÖRfer, C.; Vaisius, A.C.; Zanotti, G. The Effect of the Chemical Nature of the Side Chains of the Amatoxins in the Inhibition of Eukaryotic RNA Polymerase B. Eur. J. Biochem. 2005, 117, 161–164. [Google Scholar] [CrossRef]
  120. Aygul, N.; Duzenli, M.A.; Ozdemir, K.; Altunkeser, B.B. A case report of an unusual complication of Amanita phalloides poisoning: Development of cardiogenic shock and its successful treatment with intra-aortic balloon counterpulsation. Toxicon 2010, 55, 630–632. [Google Scholar] [CrossRef]
  121. Mount, P.; Harris, G.; Sinclair, R.; Finlay, M.; Becker, G.J. Acute renal failure following ingestion of wild mushrooms. Intern. Med. J. 2002, 32, 187–190. [Google Scholar] [CrossRef]
  122. Michelot, D.; Toth, B. Poisoning byGyromitra esculenta–a review. J. Appl. Toxicol. 1991, 11, 235–243. [Google Scholar] [CrossRef] [PubMed]
  123. Genest, K.; Hughes, D.; Rice, W. Muscarine in Clitocybe species. J. Pharm. Sci. 1968, 57, 331–333. [Google Scholar] [CrossRef] [PubMed]
  124. Curtis, D.R.; Lodge, D.; McLennan, H. The excitation and depression of spinal neurones by ibotenic acid. J. Physiol. 1979, 291, 19–28. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  125. Badham, E.R. Ethnobotany of psilocybin mushrooms, especially Psilocybe cubensis. J. Ethnopharmacol. 1984, 10, 249–254. [Google Scholar] [CrossRef]
  126. Haberl, B.; Pfab, R.; Berndt, S.; Greifenhagen, C.; Zilker, T. Case series: Alcohol intolerance with Coprine-like syndrome after consumption of the mushroomLepiota aspera(Pers., Fr.) Quél. 1886 (Freckled Dapperling). Clin. Toxicol. 2011, 49, 113–114. [Google Scholar] [CrossRef] [PubMed]
Molecules 26 01359 g001 550
Figure 1. Chemical structure of β-1, 3/1, 6-d-glucan. Glucans are long-chain polysaccharides of a glucose (hexose) monomer, which is linked in the β-1, 3 positions with a smaller side chain of β-1, 6 divaricating from the main polysaccharide chain [29].
Figure 1. Chemical structure of β-1, 3/1, 6-d-glucan. Glucans are long-chain polysaccharides of a glucose (hexose) monomer, which is linked in the β-1, 3 positions with a smaller side chain of β-1, 6 divaricating from the main polysaccharide chain [29].
Molecules 26 01359 g001
Molecules 26 01359 g002 550
Figure 2. GFP-activated bone-marrow-derived dendritic cells (BMDCs) inhibit tumor growth and increase the level of tumor-antigen-specific antibody production in mice. (A) The severity of tumor growth 20 days after LLC1 inoculation. (B) Progression of tumor volume from 10 to 20 days after LLC1 inoculation. (C) Mice serum was collected to quantify tumor-antigen-specific antibodies by a standard ELISA. Asterisks indicate data that were significantly (* p < 0.05) different from those of mice that received PBS or PBS-treated BMDCs [54].
Figure 2. GFP-activated bone-marrow-derived dendritic cells (BMDCs) inhibit tumor growth and increase the level of tumor-antigen-specific antibody production in mice. (A) The severity of tumor growth 20 days after LLC1 inoculation. (B) Progression of tumor volume from 10 to 20 days after LLC1 inoculation. (C) Mice serum was collected to quantify tumor-antigen-specific antibodies by a standard ELISA. Asterisks indicate data that were significantly (* p < 0.05) different from those of mice that received PBS or PBS-treated BMDCs [54].
Molecules 26 01359 g002
Molecules 26 01359 g003 550
Figure 3. (A) β-glucan-modified AuNRs with different concentrations of glucans (0, 1, 5, 10, and 15 mg/mL). (B) Cytotoxicity of AuNRs and AuNR-Glu against MCF-7 cells. (C) MCF-7 cell viability after photothermal treatment with 20 μg/mL AuNR-Glu irradiated by a 1064 nm laser with different power densities for 5 min. Mean ± standard deviation, N = 3, * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001. (D) Fluorescence images after photothermal treatment with 20 μg/mL AuNR-Glu irradiated by a 1064 nm laser with a (i,vi) 0, (ii,vii) 0.25, (iii,viii) 0.5, (iv,ix) 0.75, and (v,x) 1.0 W/cm2 power density for 5 min. Cells that stably expressed GFP on their tubulin (live: green) were stained with propidium iodide (dead: red) after 24 h post incubation (scale bars: 20 μm). The cells without AuNR-Glu were used as the control [60].
Figure 3. (A) β-glucan-modified AuNRs with different concentrations of glucans (0, 1, 5, 10, and 15 mg/mL). (B) Cytotoxicity of AuNRs and AuNR-Glu against MCF-7 cells. (C) MCF-7 cell viability after photothermal treatment with 20 μg/mL AuNR-Glu irradiated by a 1064 nm laser with different power densities for 5 min. Mean ± standard deviation, N = 3, * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001. (D) Fluorescence images after photothermal treatment with 20 μg/mL AuNR-Glu irradiated by a 1064 nm laser with a (i,vi) 0, (ii,vii) 0.25, (iii,viii) 0.5, (iv,ix) 0.75, and (v,x) 1.0 W/cm2 power density for 5 min. Cells that stably expressed GFP on their tubulin (live: green) were stained with propidium iodide (dead: red) after 24 h post incubation (scale bars: 20 μm). The cells without AuNR-Glu were used as the control [60].
Molecules 26 01359 g003
Molecules 26 01359 g004 550
Figure 4. (A) Representative bright-field images (200× magnification) of human cancer cells taken at 48 h after treatment with the P. ravenelii MeOH extract at the indicated concentrations. Magnified regions are shown as insets. (B) Viability of human cancer cell lines after treatment with the P. ravenelii MeOH extract at the indicated concentrations (upper panels) and IC50 values of the extract for the corresponding cell line (lower panels). Data are representative of three independent experiments (n = 3) and are presented as means ± SD. Scale bar: 100 µm [61].
Figure 4. (A) Representative bright-field images (200× magnification) of human cancer cells taken at 48 h after treatment with the P. ravenelii MeOH extract at the indicated concentrations. Magnified regions are shown as insets. (B) Viability of human cancer cell lines after treatment with the P. ravenelii MeOH extract at the indicated concentrations (upper panels) and IC50 values of the extract for the corresponding cell line (lower panels). Data are representative of three independent experiments (n = 3) and are presented as means ± SD. Scale bar: 100 µm [61].
Molecules 26 01359 g004
Molecules 26 01359 g005 550
Figure 5. Antioxidant activities of water-soluble polysaccharides (RVLWPs) and alkaline-soluble polysaccharides (RVLAPs): (A) scavenging of DPPH radicals; (B) inhibitory effect on lipid peroxidation; (C) hydrogen peroxide scavenging activity; (D) reducing power; (E) Fe2+ ion-chelating activity. The values are representative of three separate experiments [83]. The results are presented as the mean ± standard deviation (SD) from three independent experiments (n = 3).
Figure 5. Antioxidant activities of water-soluble polysaccharides (RVLWPs) and alkaline-soluble polysaccharides (RVLAPs): (A) scavenging of DPPH radicals; (B) inhibitory effect on lipid peroxidation; (C) hydrogen peroxide scavenging activity; (D) reducing power; (E) Fe2+ ion-chelating activity. The values are representative of three separate experiments [83]. The results are presented as the mean ± standard deviation (SD) from three independent experiments (n = 3).
Molecules 26 01359 g005
Molecules 26 01359 g006 550
Figure 6. Effects of Cantharellus cibarius on iron deposition in mice liver. Representative microscopic photographs of livers stained with Prussian blue (400× magnification). (A) Control group, (B) iron overloaded group, (C) DFO group, (D) ethyl acetate extract group, and (E) methanolic extract group) [87].
Figure 6. Effects of Cantharellus cibarius on iron deposition in mice liver. Representative microscopic photographs of livers stained with Prussian blue (400× magnification). (A) Control group, (B) iron overloaded group, (C) DFO group, (D) ethyl acetate extract group, and (E) methanolic extract group) [87].
Molecules 26 01359 g006
Table
Table 1. A scientific and common name of mushrooms and their significant constituents [15]. (GLPS = Ganoderma lucidum polysaccharide; PSP = polysaccharide peptide; PSK = polysaccharide K.).
Table 1. A scientific and common name of mushrooms and their significant constituents [15]. (GLPS = Ganoderma lucidum polysaccharide; PSP = polysaccharide peptide; PSK = polysaccharide K.).
Scientific NameCommon NameSpecific ConstituentType of Constituent
Agaricus blazeiAgaricusβ-d-glucanPolysaccharide
Ganoderma lucidumReishi, lingzhiGanoderic acidProtein
DanoderiolProtein
Danderenic acidProtein
Lucidenic acidProtein
GLPSPolysaccharide
Cordyceps sinesisCordyceps, caterpillar mushroomAdenosineNucleotide
CordycepinNucleotide
Trametes versicolor (formerly Coriolus versicolor)Turkey tailPSPolysaccharide peptide
PSKPolysaccharide peptide
Grifolia frondosaMaitakeGrifolanPolysaccharide
D-fraction
MD-fractionPolysaccharide
Table
Table 2. The effects of different mushrooms on the cellular response.
Table 2. The effects of different mushrooms on the cellular response.
MushroomModelCompoundResponseReference
ButtonIn vivoHot water extractUpregulation of CD69, CD49 T, CD3, CD19, NK activity, phagocytosis of spleen cells, and decrease the liver and spleen weight[63,64]
Enhancement in the level of the interleukin (IL) IL-1, IL-6, TNF-α, and IL-1β[26,27]
MaitakeIn vivoExtractIncreased cell growth and differentiation[65]
Upregulation of tumor-specific CD8+, CD4+ T cells, NK activity, T-cell infiltration, and decrease the Treg cells activity[50]
ReishiIn vivoPolysaccharides and extractEnhancement of CD56, NK cells, phagocytosis, CD8+, CD4+ cells activity, and decrease the cancerous cell activities such as cell growth, and adhesion[66,67,68]
CordycepsIn vitroCordycepinDecreases the activity of matrix metallopeptidase 9 (MMP-9), and NF-κB protein complex[69]
Inhibition of TNF-α, IL-1β, NO, prostaglandin (E2)[30]
Turkey TailIn vivoPowderIncrease lymphocyte count, NK activity, CD8+ T cells, and CD19+ B cells activity[70]
ShiitakeIn vitroExtractInhibition of chicken tumor cells growth and increased the secretion level of interferon-α (IFN-α), IL-1β, IL-6, IL-12, IL-15, IL-18, and tumor necrosis factor superfamily 15 (TNFSF15)[71]
Cracked-cap PolyporeIn vitro and vivoExtractSuppressed the growth of tumor cells[72]
Black HoofEnhancement in cell proliferation, migration, tube formation and phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2[73]
Pleurotus floridaIn vitroExtractAnti-inflammatory and antiplatelet-aggregating potential[74]
Albatrellus confluencesIn vitroExtractAntitumor activity and upregulation of death-associated protein kinase 1 (DAPK1)[75,76]
Table
Table 3. Mushrooms extract exhibiting immunomodulatory and other activities.
Table 3. Mushrooms extract exhibiting immunomodulatory and other activities.
Mushroom SpeciesActive MaterialsFunctionsReference
Agaricus bisporusMonounsaturated fatty acids and ergosterolAntioxidant and antimicrobial properties[93,94]
Agaricus brasiliensisPolyunsaturated fatty acids
Agaricus bisporusLectinsImmunomodulatory
Agaricus blazeiPolysaccharides
Phellinus linteusPolysaccharidesImmunomodulatory[95,96,97]
Phellinus igniarius
Phellinus sp.Antiaging activity
Ficus caricaPolysaccharidesImmunomodulatory activity[98]
Pleurotus eryngiiProtein/polyphenolsImmunomodulatory and anti-inflammatory[99,100,101,102,103,104,105]
Pleurotus tuber-regiumPolysaccharidesImmunomodulatory and antitumor
Pleurotus citrinopileatusProtein PCP-3AImmunomodulatory and anti-inflammatory
Pulveroboletus raveneliiVulpinic acidAnticancerous[105]
Prunella vulgarisHeteropolysaccharidesImmunomodulatory[106]
Lentinula edodesPolysaccharidesImmunomodulatory[107]
Talinum triangularePolysaccharidesAntitumor efficacy[108]
Tremella fuciformisBerk extractAnti-inflammatory[109]
Antrodia camphorataProteinImmunomodulatory[110]
Poria cocosProteinImmunomodulatory[111]
Ganoderma atrumProteinAnticancerous[112]
Tricholoma matsutakeα-Glucan–protein complexImmunomodulatory[113]
Hericium erinaceusPolysaccharidesImmunomodulatory[114]
Flammulina velutipesProteinAnticancerous[115]
Table
Table 4. Clinical manifestations, action sites, and toxicity potential of the indicated mushrooms (GIT, gastrointestinal tract; ANS, autonomic nervous system; CNS, central nervous system).
Table 4. Clinical manifestations, action sites, and toxicity potential of the indicated mushrooms (GIT, gastrointestinal tract; ANS, autonomic nervous system; CNS, central nervous system).
SpeciesToxic SubstanceAction SitesToxic SyndromeMortality RateReference
Amanita phalloides
Amanita verna
Amanita bisporigera
Amanita virosa		Amatoxins, phallotoxinsLive, kidney, GITDelayed liver toxicity and gastroenteritis~2–30%[120]
Cortinarius orellanus
Cortinarius speciosissinus		OrellanineKidney, GITDelayed renal failureVery less[121]
Gyromitra esculenta
Gyromitra infula
Chrysina macropus		GyromitrinLiver, blood, GIT, CNSDelayed gastroenteritis and liver toxicity0–10%[122]
Clitocybe dealbata
Clitocybe illudens
Boletus calopus		MuscarineANSVomiting, salivation, diarrheaVery less[123]
Amanita muscaria
Amanita pantherina
Amanita gemmata		Ibotenic acidCNSHallucinations, seizures, agitationVery less[124]
Psilocybe cubensis
Psilocybe Mexicana
Conocybe cyanopus		PsilocybinCNSHallucinationsVery less[125]
Coprinus atramentariusCoprine-Anxiety, headache, chest painVery less[126]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Patel, D.K.; Dutta, S.D.; Ganguly, K.; Cho, S.-J.; Lim, K.-T. Mushroom-Derived Bioactive Molecules as Immunotherapeutic Agents: A Review. Molecules 2021, 26, 1359. https://doi.org/10.3390/molecules26051359

AMA Style

Patel DK, Dutta SD, Ganguly K, Cho S-J, Lim K-T. Mushroom-Derived Bioactive Molecules as Immunotherapeutic Agents: A Review. Molecules. 2021; 26(5):1359. https://doi.org/10.3390/molecules26051359

Chicago/Turabian Style

Patel, Dinesh K., Sayan Deb Dutta, Keya Ganguly, Seong-Jun Cho, and Ki-Taek Lim. 2021. "Mushroom-Derived Bioactive Molecules as Immunotherapeutic Agents: A Review" Molecules 26, no. 5: 1359. https://doi.org/10.3390/molecules26051359

APA Style

Patel, D. K., Dutta, S. D., Ganguly, K., Cho, S. -J., & Lim, K. -T. (2021). Mushroom-Derived Bioactive Molecules as Immunotherapeutic Agents: A Review. Molecules, 26(5), 1359. https://doi.org/10.3390/molecules26051359

Article Metrics

Back to TopTop