Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials
Abstract
:1. Introduction
2. Bioactive Compounds in Medicinal Mushrooms: Effects and Mechanisms of In Vitro and In Vivo Preclinical Studies
2.1. Coriolus versicolor (L.) Quél.
2.2. Ganoderma lucidum (Curtis) P. Karst.
2.3. Lentinula edodes (Berk.) Pegler
2.4. Pleurotus spp.
2.5. Grifola frondosa (Dicks.) Gray
2.6. Hericium erinaceus (Bull.) Pers.
2.7. Antrodia cinnamomea T.T. Chang and W.N. Chou
2.8. Agaricus bisporus (J.E. Lange) Imbach
2.9. Agaricus blazei Murrill
3. Mushroom Therapeutic Use: An Overview of Dietary Supplement Affairs
4. Pharmacological Activities of Mushrooms: Medical Evidence through Clinical Trials
4.1. Medicinal Mushrooms and Cancer Clinical Studies
4.2. Medicinal Mushrooms and Diabetes, Hyperglycemia, Hyperlipidemia, and Cardiovascular Disorder Clinical Studies
4.3. Medicinal Mushrooms and Neuron Health Clinical Studies
4.4. Medicinal Mushrooms in Clinical Studies on Other Medical Topics
5. Discussion
6. Concluding Remarks
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ABM | Agaricus blazei mushroom |
ACC | Acetyl-CoA Carboxylase |
ALT | Alanine Aminotransferase |
AOX | Alternative Oxidase |
ASCT | Autologous Stem Cell Transplantation |
AST | Aspartate Aminotransferase |
ATA | Anctin-A |
BG | Antibody Response to β-glucan |
BRMs | Biological Response Modifiers |
CAM | Complementary Alternative Medicine |
cAMP | Cyclic Adenosine Monophosphate |
CDC | Complement-Dependent Cytotoxicity |
CIM | Complementary Integrated Medicine |
CLA | Conjugated Linoleic Acid |
ConA | Concanavalin A |
DBP | Diastolic Blood Pressure |
DCs | Dendritic Cells |
DC-STAMP | Dendritic Cell-Specific Transmembrane Protein |
ER | Endoplasmic Reticulum |
EFSA | European Food Safety Authority |
EORTC-QLQ-C30 | European Organisation Research Treatment Cancer Core Quality of Life Questionnaire C30 |
FAC | Fanconi Anemia (FA) group C gene |
FACTF | Functional Assessment of Cancer Therapy Fatigue |
FAS | Fatty Acid Synthase |
FDA | American Food and Drug Administration |
FSG | Fasting Serum Glucose |
FIPs | Fungal Immunomodulatory Proteins |
FSI | Fasting Serum Insulin |
GFP | Grifola frondosa Polysaccharide |
hAMSCs | Human Amniotic Mesenchymal Cells |
HADS | The Hospital Anxiety and Depression Scale |
HDL | High-Density Lipoprotein |
HDL-C | High-Density Lipoprotein Cholesterol |
HLA | Human Leukocyte Antigens |
HOMA-IR | Homeostasis Model Assessment of Insulin Resistance |
iROS | Intracellular Reactive Oxygen Species |
IgG | Immunoglobulin |
IL | Interleukin |
LDL | Low Density Lipoproteins |
LMW | Low-Molecular-Weight |
MPP | 1-methyl-4-phenylpyridinium |
NOS | Nitric Oxide Synthase |
IR | Insulin Receptor |
IRS-1 | Insulin Receptor Substrate-1 |
LPS | Lipopolysaccharide |
MAPK | Mitogen-Activated Protein Kinase |
MITF | Microphthalmia-Associated Transcription Factor |
MMs | Medicinal Mushrooms |
MMP-2 | Matrix Metalloproteinase-2 |
NK | Natural Killer |
NP | Nanoparticle |
PAMP | Pathogen-Associated Molecular Pattern |
PBMCs | Peripheral Blood Mononuclear Cells |
PD | Parkinson disease |
PHA | Phytohemagglutinin |
PSA | Prostate-Specific Antigen |
PSK | Polysaccharide-K (Krestin) |
PSP | Polysaccharide Peptide |
RCT | Randomized Clinical Trial |
SBP | Systolic Blood Pressure |
SCFA | Short Chain Fatty Acid |
SREBP-1c | Sterol Regulatory Element-Binding Protein 1 |
TAC | Transverse Aortic Constriction |
TGs | Plasma Triglycerides |
TNBC | Triple-Negative Breast Cancer |
TNF-α | Tumor Necrosis Factor-α |
TRP-1 | Tyrosinase-Related Protein-1 |
VEGF | Vascular Endothelial Growth Factor |
References
- Wasser, S.P. Medicinal mushroom science: Current perspectives, advances, evidences, and challenges. Biomed. J. 2014, 37, 345–356. [Google Scholar] [CrossRef] [PubMed]
- Elkhateeb, W.A. What medicinal mushroom can do? Chem. Res. J. 2020, 5, 106–118. [Google Scholar]
- Guggenheim, A.G.; Wright, K.M.; Zwickey, H. Immune modulation from five major mushrooms: Application to integrative oncology. Integr. Med. (Encinitas) 2014, 13, 32–44. [Google Scholar] [PubMed]
- Spelman, K.; Sutherland, E.; Bagade, A. Neurological activity of Lion’s mane (Hericium erinaceus). J. Restor. Med. 2017, 6, 16–26. [Google Scholar] [CrossRef] [Green Version]
- Jeitler, M.; Michalsen, A.; Frings, D.; Hübner, M.; Fischer, M.; Koppold-Liebscher, D.A.; Murthy, V.; Kessler, C.S. Significance of medicinal mushrooms in integrative oncology: A narrative review. Front. Pharmacol. 2020, 11, 580656. [Google Scholar] [CrossRef]
- Frost, M. Three popular medicinal mushroom supplements: A review of human clinical trials. 2016, All Faculty Publications. 1609. Available online: https://scholarsarchive.byu.edu/facpub/1609.
- El Enshasy, H.A.; Hatti-Kaul, R. Mushroom immunomodulators: Unique molecules with unlimited applications. Trends Biotechnol. 2013, 31, 668–677. [Google Scholar] [CrossRef] [PubMed]
- Popović, V.; Žicković, J.; Davidović, S.; Stevanović, M.; Stojković, D. Mycotherapy of Ccancer: An update on cytotoxic and antitumor activities of mushrooms, bioactive principles and molecular mechanisms of their action. Curr. Top. Med. Chem. 2013, 13, 2791–2806. [Google Scholar] [CrossRef] [PubMed]
- Zhao, S.; Gao, Q.; Rong, C.; Wang, S.; Zhao, Z.; Liu, Y.; Xu, J. Immunomodulatory effects of edible and medicinalmushrooms and their bioactive immunoregulatory products. J. Fungi 2020, 6, 269. [Google Scholar] [CrossRef]
- Wang, Z.; Dong, B.; Feng, Z.; Yu, S.; Bao, Y. A study on immunomodulatory mechanism of Polysaccharopeptide mediated by TLR4 signaling pathway. BMC Immunol. 2015, 16, 34. [Google Scholar] [CrossRef] [Green Version]
- Saleh, M.H.; Rashedi, I.; Keating, A. Immunonodulatory properties of Coriuolus versicolor: The role of Polysaccharopeptide. Front. Immunol. 2017, 8, 1087. [Google Scholar] [CrossRef] [Green Version]
- Chang, Y.; Zhang, M.; Jiang, Y.; Liu, Y.; Luo, H.; Hao, C.; Zeng, P.; Zhang, L. Preclinical and clinical studies of Coriolus versicolor polysaccharopeptide as an immunotherapeutic in China. Discov. Med. 2017, 23, 207–219. [Google Scholar] [PubMed]
- Yang, X.; Sit, W.; Chan, D.K.; Wan, J.M. The cell death process of the anticancer agent polysaccharide-peptide (PSP) in human promyelocytic leukemic HL-60 cells. Oncol. Rep. 2005, 13, 1201–1210. [Google Scholar] [CrossRef] [PubMed]
- Rodríguez-Valentín, M.; López, S.; Rivera, M.; Ríos-Olivares, E.; Cubano, L.; Boukli, N.M. Naturally derived anti-HIV polysaccharides peptide (PSP) triggers a toll-like receptor 4-dependent antiviral immune response. J. Immunol. Res. 2018, 2018. [Google Scholar] [CrossRef] [PubMed]
- 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]
- Ooi, V.E.C.; Liu, F. Immunomodulation as anti-cancer activity of polysaccharide-protein complexes. Curr. Med. Chem. 2000, 7, 715–729. [Google Scholar] [CrossRef] [Green Version]
- Fritz, H.; Kennedy, D.A.; Ishii, M.; Fergusson, D.; Fernandes, R.; Cooley, K.; Suueley, D. Polysaccharide K and Coriolus versicolor extracts for lung cancer: A systematic review. Integr. Cancer Ther. 2015, 14, 201–211. [Google Scholar] [CrossRef]
- Ito, G.; Tanaka, H.; Ohira, M.; Yoshii, M.; Muguruma, K.; Kubo, N.; Yashiro, M.; Yamada, N.; Maeda, K.; Sawada, T.; et al. Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I. Exp. Ther. Med. 2012, 3, 925–930. [Google Scholar] [CrossRef] [Green Version]
- Xu, S.; Ye, B.; Dou, Y.; Hu, M.; Rong, X. Coriolus versicolor polysaccharide regulates inflammatory cytokines expression and ameliorates hyperlipidemia in mice. Acta Sci. Natur. Univ. Nankaiensis 2016, 49, 81–87. [Google Scholar]
- Bulam, S.; Üstün, N.Ş.; Pekşen, A. Health benefits of Ganoderma lucidum as a medicinal mushroom. TURJAF 2019, 7(sp 1), 84–93. [Google Scholar] [CrossRef] [Green Version]
- Trigos, Á.; Suárez Medellín, J. Biologically active metabolites of the genus Ganoderma: Three decades of myco-chemistry research. Rev. Mex. Mic. 2011, 34, 63–83. [Google Scholar]
- Lee, I.; Kim, J.; Ryio, I.; Kim, Y.; Choo, S.; Yoo, I.; Min, B.; Na, M.; Hattori, M.; Bae, K. Lanostane triterpenes from Ganoderma lucidum suppress the adipogenesis in 3T3-L1 cells through down-regulation of SREBP-1c. Bioorganic Med. Chem. Lett. 2010, 20, 5577–5581. [Google Scholar] [CrossRef] [PubMed]
- Miyamoto, I.; Liu, J.; Shimizu, K.; Sato, M.; Kukita, A.; Kukita, T.; Kondo, R. Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum. Eur, J. Pharmacol. 2009, 602, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Xie, Y.; Yang, F.; Tan, W.; Li, X.; Jiao, C.; Huang, R.; Yang, B.B. The anti-cancer components of Ganoderma lucidum possesses cardiovascular protective effect by regulating circular RNA expression. Oncoscience 2016, 3(7–8), 203–207. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Kim, H.; Kim, J.H.; Kwon, O.; Son, E.; Lee, C.; Park, Y. Effects of Ganodermanondiol, a new melanogenesis inhibitor from the medicinal mushroom Ganoderma lucidum. Int. Mol. Sci. 2016, 17, 1798. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, Y.; Yuan, H.; Luo, Y.; Zhao, Y.; Xiao, J. Ganoderic acid D protects human amniotic mesenchymal stem cells against oxidative stress-induced senescence through the PERK/NRF2 signaling pathway. Oxid. Med. Cell. Longev. 2020, 2020. [Google Scholar] [CrossRef]
- Ina, K.; Kataoka, T.; Ando, T. The use of lentinan for treating gastric cancer. Anticancer Agents Med. Chem. 2013, 13, 681–688. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Y.; Zhang, M.; Jiang, Y.; Li, X.; He, Y.; Zeng, P.; Guo, Z.; Chang, Y.; Luo, H.; Liu, Y.; et al. Lentinan as an immunotherapeutic for treating lung cancer: A review of 12 years clinical studies in China. J. Cancer Res. Clin. Oncol. 2018, 144, 2177–2186. [Google Scholar] [CrossRef]
- Ahn, H.; Jeon, E.; Kim, J.; Kang, S.; Yoon, S.; Ko, H.; Kim, P.; Lee, G. Lentinan from shiitake selectively attenuates AIM2 and non-canonical inflammasome activation while inducing pro-inflammatory cytokine production. Sci. Rep. 2017, 7, 1314. [Google Scholar] [CrossRef] [Green Version]
- Li, X.; Zhang, M. In vitro inhibitory effects of lentinan on rat glioma cells. Biomed. Res. 2014, 25, 39–44. [Google Scholar]
- Deng, S.; Zhang, G.; Kuai, J.; Fan, P.; Wang, X.; Zhou, P.; Yang, D.; Zheng, X.; Liu, X.; Wu, Q.; et al. Lentinan inhibits tumor angiogenesis via interferon γ and in a T cell independent manner. J. Exp. Clin. Cancer Res. 2018, 37, 270. [Google Scholar] [CrossRef] [Green Version]
- Finimundy, T.C.; Gambato, G.; Fontana, R.; Camassola, M.; Salvador, M.; Moura, S.; Hess, J.; Henriques, A.P.; Dillon, A.J.P.; Roesch-Ely, M. Aqueous extracts of Lentinula edodes and Pleurotus sajor-caju exhibit high antioxidant capability and promising in vitro antitumor activity. Nutr. Res. 2013, 33, 76–84. [Google Scholar] [CrossRef] [PubMed]
- Sarangi, I.; Ghosh, D.; Bhutia, S.K.; Mallick, S.K.; Maiti, T.K. Anti-tumor and immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans. Int. Immunopharmacol. 2006, 6, 1287–1297. [Google Scholar] [CrossRef] [PubMed]
- Jedinak, A.; Sliva, D. Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway. Int. J. Oncol. 2008, 33, 1307–1313. [Google Scholar] [PubMed]
- Jedinak, A.; Dudhgaonkar, S.; Wu, Q.; Simon, J.; Silva, D. Anti-inflammatory activity of edible oyster mushroom is mediated through the inhibition of NF-κB and AP-1 signaling. Nutr. J. 2011, 10, 52. [Google Scholar] [CrossRef] [Green Version]
- Sun, Y.; Hu, X.; Li, W. Antioxidant, antitumor and immunostimulatory activities of the polypeptide from Pleurotus eryngii mycelium. Int. J. Biol. Macromol. 2017, 97, 323–330. [Google Scholar] [CrossRef]
- Fontana, S.; Flugy, A.; Schillaci, O.; Cannizzaro, A.; Gargano, M.L.; Saitta, A.; De Leo, G.; Venturella, G.; Alessandro, R. In vitro antitumor effects of the cold-water extracts of Mediterranean species of genus Pleurotus (higher Basidiomycetes) on human colon cancer cells. Int. J. Med. Mushrooms 2014, 16, 49–63. [Google Scholar] [CrossRef] [Green Version]
- Alonso, E.N.; Orozco, M.; Nieto, A.E.; Balogh, G.A. Genes related to suppression of malignant phenotype induced by Maytake D-fraction in breast cancer cells. J. Med. Food 2013, 16, 602–617. [Google Scholar] [CrossRef] [Green Version]
- Alonso, E.N.; Ferronato, M.J.; Gandini, N.A.; Fermento, M.E.; Obiol, D.J.; López Romero, A.; Arévalo, J.; Villegas, M.E.; Facchinetti, M.M.; Curino, A.C. Antitumoral effects of D-fraction from Grifola frondosa (Maitake) mushroom in breast cancer. Nutr. Cancer 2017, 69, 29–43. [Google Scholar] [CrossRef]
- Alonso, E.N.; Ferronato, M.J.; Fermento, M.E.; Gandini, N.A.; López Romero, A.; Guevara, J.A.; Facchinetti, M.M.; Curino, A.C. Antitumoral and antimetastatic activity of Maitake D-fraction in triple-negative breast cancer cells. Oncotarget 2018, 9, 23396–23412. [Google Scholar] [CrossRef] [Green Version]
- Xiao, C.; Wu, Q.; Xie, Y.; Zhang, J.; Tan, J. Hypoglicemic effects of Grifola frondosa (M) polysaccharides F2 and F3 through improvement of insulin in diabetic rats. Food Funct. 2015, 6, 3567–3575. [Google Scholar] [CrossRef]
- Cui, F.; Zan, X.; Li, Y.; Sun, W.; Yang, Y.; Ping, L. Grifola frondosa glycoprotein GFG-3a arrests S phase, alters proteome, and induces apoptosis in human gastric cancer cells. Nutr. Cancer 2016, 68, 267–279. [Google Scholar] [CrossRef] [PubMed]
- Kawagishi, H.; Zhuang, C. Compounds for dementia from Hericium erinaceum. Drugs Future 2008, 33, 149–155. [Google Scholar] [CrossRef]
- Chong, P.S.; Fung, M.; Wong, K.H.; Lim, L.W. Therapeutic potential of Hericium erinaceus for depressive disorders. Int. J. Mol. Sci. 2020, 21, 163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuo, H.; Lu, C.; Shen, C.; Tung, S.; Hsieh, M.; Lee, K.; Lee, L.; Chen, C.; Teng, C.; Huang, W.; et al. Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade. J. Transl. Med. 2016, 14, 78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, I.; Lee, L.; Tzeng, T.; Chen, W.; Chen, Y.; Shiao, Y.; Chen, C. Neurohealth properties of Hericium erinaceus mycelia enriched with erinacines. Behav. Neurol. 2018, 2018. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuo, H.; Kuo, Y.; Lee, K.; Hsieh, M.; Huang, C.; Hsieh, Y.; Lee, K.; Kuo, H.; Lee, L.; Chen, W.; et al. A comparative proteomic analysis of Erinacine A’s inhibition of gastric cancer cell viability and invasiveness. Cell. Physiol. Biochem. 2017, 43, 195–208. [Google Scholar] [CrossRef]
- Lee, K.; Lee, K.-F.; Tung, S.; Huang, W.; Lee, L.; Chen, W.; Chen, C.; Teng, C.; Shen, C.; Hsieh, M.; et al. Induction apoptosis of erinacine A in human colorectal cancer cells involving the expression of TNFR, Fas, and Fas ligand via the JNK/p300/p50 signaling pathway with histone acetylation. Front. Pharmacol. 2019, 10, 1174. [Google Scholar] [CrossRef]
- Wang, L.; Huang, C.; Chen, Y.; Chen, C.; Chen, C.; Chuang, C. Anti-inflammatory effect of erinacine C on NO production through down-regulation of NF-κB and activation of Nrf2-mediated HO-1 in BV2 microglial cells treated with LPS. Molecules 2019, 24, 3317. [Google Scholar] [CrossRef] [Green Version]
- Kumar, K.J.S.; Vani, M.G.; Hsieh, H.W.; Lin, C.C.; Wang, S.Y. Antcin-A modulates epithelial-to-mesenchymal transition and inhibits migratory and invasive potentials of human breast cancer cells via p53-mediated miR-200c activation. Planta Med. 2019, 85, 755–765. [Google Scholar] [CrossRef]
- Chen, Y.; Liu, Y.; El-Shazly, M.; Wu, T.; Chang, J.; Wu, Y. Antrodia cinnamomea, a treasured medicinal mushroom, induces growth arrest in breast cancer cells, T47D cells: New mechanisms emerge. Int. J. Mol. Sci. 2019, 20, 833. [Google Scholar] [CrossRef] [Green Version]
- Blumfield, L.; Abbott, K.; Duve, E.; Cassettari, T.; Marshall, S.; Fayet-Moore, F. Examining the health effects and bioactive components in Agaricus bisporus mushrooms: A scoping review. J. Nutr. Biochem. 2020, 84, 108453. [Google Scholar] [CrossRef] [PubMed]
- Atila, F.; Owaid, M.N.; Ali Shariati, M. The nutritional and medical benefits of Agaricus bisporus: A review. J. Microbiol. Biotechnol. Food Sci. 2017, 7, 281–286. [Google Scholar] [CrossRef]
- Adams, L.S.; Phung, S.; Wu, X.; Ki, L.; Chen, S. White button mushroom (Agaricus bisporus) exhibits antiproliferative and proapoptotic properties and inhibits prostate tumor growth in athymic mice. Nutr Cancer. 2008, 60, 44–56. [Google Scholar] [CrossRef]
- Ahmed, O.M.; Ebaid, H.; El-Nahass, S.; Ragab, M.; Alhazza, I.M. Nephroprotective Effect of Pleurotus ostreatus and Agaricus bisporus Extracts and Carvedilol on Ethylene Glycol-Induced Urolithiasis: Roles of NF-κB, p53, Bcl-2, Bax and Bak. Biomolecules 2020, 10, 1317. [Google Scholar] [CrossRef] [PubMed]
- Muszynska, B.; Grzywacz, A.; Kala, K.; Gdula-Argasinska, J. Anti-Inflammatory Potential of In Vitro Cultures of the White Button Mushroom, Agaricus bisporus (Agaricomycetes), in Caco-2 Cells. Int. J. Med. Mushrooms 2018, 20, 129–139. [Google Scholar] [CrossRef] [PubMed]
- Gargano, M.L.; Van Griensven, L.J.L.D.; Isikhuemhen, O.S.; Lindequist, U.; Venturella, G.; Wasser, S.P.; Zervakis, G.I. Medicinal mushrooms: Valuable biological resources of high exploitation potential. Plant Biosyst. 2017, 151, 548–565. [Google Scholar] [CrossRef]
- Mizuno, T. Medicinal Properties and Clinical Effects of Culinary-Medicinal Mushroom Agaricus blazei Murrill (Agaricomycetideae) (Review). Int. J. Med. Mushrooms 2002, 4, 299–312. [Google Scholar] [CrossRef]
- Murakawa, K.; Fukunaga, K.; Tanouchi, M.; Hosokawa, M.; Hossain, Z.; Takahashi, K. Therapy of myeloma in vivo using marine phospholip in combination with Agaricus blazei Murill as an immune respond activator. J. Oleo Sci. 2007, 56, 179–188. [Google Scholar] [CrossRef] [Green Version]
- Niu, Y.C.; Liu, J.C.; Zhao, X.M.; Wu, X.X. A low molecular weight polysaccharide isolated from Agaricus blazei supresses tumor growth and angiogenesis in vivo. Oncol Rep. 2009, 21, 145–152. [Google Scholar] [CrossRef]
- Lima, C.U.J.O.; Gris, E.F.; Karnikowski, M.G.O. Antimicrobial properties of the mushroom Agaricus blazei–integrative review. Rev. Bras. Farmacogn. 2016, 26, 780–786. [Google Scholar] [CrossRef]
- Ishibashi, K.-I.; Motoi, M.; Liu, Y.; Miura, N.N.; Adachi, Y.; Ohno, N. Effect of Oral Administration of Dried Royal Sun Agaricus, Agaricus brasiliensis S. Wasser et al. (Agaricomycetideae), Fruit Bodies on Anti-β-Glucan Antibody Titers in Humans. Int. J. Med. Mushrooms 2009, 11, 117–131. [Google Scholar] [CrossRef] [Green Version]
- Ellertsen, L.K.; Hetland, G. An extract of the medicinal mushroom Agaricus blazei Murill can protect against allergy. Clin Mol Allergy 2009, 7, 1–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- MSD Manual. Professional Edition. Available online: https://www.msdmanuals.com/professional (accessed on December 2020).
- Pirillo, A.; Capatano, A.L. Nutraceuticals: Definitions, European regulations and clinical applications (Nutraceutica: Definizione, regolamentazione e applicazioni). Giorn. Ital. Farmacoecon. Farmacoutiliz. 2014, 6, 23–30. [Google Scholar]
- Zhao, H.; Zhang, Q.; Zhao, L.; Huang, X.; Wang, J.; Kang, X. Spore powder of Ganoderma lucidum improves cancer-related fatigue in breast cancer patients undergoing endocrine therapy: A pilot clinical trial. Evid. Based Complementary Altern. Med. 2012, 2012, 809614. [Google Scholar] [CrossRef] [Green Version]
- Ahn, W.; Kim, D.; Chae, G.; Lee, J.; Bae, S.; Sin, J.; Kim, Y.; Namkoong, S.; Lee, I.P. Natural killer cell activity and quality of life were improved by consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecological cancer patients undergoing chemotherapy. Int. J. Gynecol. Cancer. 2004, 14, 589–594. [Google Scholar] [CrossRef]
- Yoshimura, K.; Kamoto, T.; Ogawa, O.; Matsui, S.; Tsuchiya, N.; Tada, H.; Murata, K.; Yoshimura, K.; Habuchi, T.; Fukushima, M. Medical mushrooms used for biochemical failure after radical treatment for prostate cancer: An open-label study. Int. J. Urol. 2010, 17, 548–554. [Google Scholar] [CrossRef]
- Ohno, S.; Sumiyoshi, Y.; Hashine, K.; Shirato, A.; Kyo, S.; Inoue, M. Phase I clinical study of the dietary supplement, Agaricus blazei Murill, in cancer patients in remission. Evid. Based Complementary Altern. Med. 2011, 2011. [Google Scholar] [CrossRef] [Green Version]
- Hetland, G.; Tangen, J.; Mahmood, F.; Mirlashari, M.R.; Nissen-Meyer, L.S.H.; Nentwich, I.; Therkelsen, S.P.; Tjønnfjord, G.E.; Johnson, E. Antitumor, anti-inflammatory and antiallergic effects of Agaricus blazei mushroom extract and the related medicinal Basidiomycetes mushrooms, Hericium erinaceus and Grifola frondosa: A review of preclinical and clinical studies. Nutrients 2020, 12, 1339. [Google Scholar] [CrossRef]
- Tangen, J.; Tierens, A.; Caers, J.; Binsfeld, M.; Olstad, O.K.; Trøseid, A.S.; Wang, J.; Tjønnfjord, G.E.; Hetland, G. Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: A randomized, double blinded clinical study. Biomed. Res. Int. 2015, 2015, 718539. [Google Scholar] [CrossRef] [Green Version]
- Kodama, N.; Komuta, K.; Nanba, H. Can maitake MD-fraction aid cancer patients? Altern. Med. Rev. 2002, 7, 236–239. [Google Scholar]
- Deng, G.; Lin, H.; Seidman, A.; Fornier, M.; D’Andrea, G.; Wesa, K.; Yeung, S.; Cunningham-Rundles, S.; Vickers, A.J.; Cassileth, B. A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: Immunological effects. J. Cancer Res. Clin. Oncol. 2009, 135, 1215–1221. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wesa, K.M.; Cunningham-Rundles, S.; Klimek, V.M.; Vertosick, E.; Coleton, M.I.; Yeung, K.S.; Lin, H.; Nimer, S.; Cassileth, B.R. Maitake mushroom extract in myelodysplastic syndromes (MDS): A phase II study. Cancer Immunol. Immunother. 2015, 64, 237–247. [Google Scholar] [CrossRef] [Green Version]
- Tsang, K.W.; Lam, C.L.; Yan, C.; Mak, J.C.; Ooi, G.C.; Ho, J.C.; Lam, B.; Man, R.; Sham, J.S.; Lam, W.K. Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer. Respir. Med. 2003, 97, 618–624. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Akagi, J.; Baba, H. PSK may suppress CD57(+) T cells to improve survival of advanced gastric cancer patients. Int. J. Clin. Oncol. 2010, 15, 145–152. [Google Scholar] [CrossRef] [PubMed]
- Miyake, Y.; Nishimura, J.; Kato, T.; Ikeda, M.; Tsujie, M.; Hata, T.; Takemasa, I.; Mizushima, T.; Yamamoto, H.; Sekimoto, M.; et al. Phase III trial comparing UFT + PSK to UFT + LV in stage IIB, III colorectal cancer (MCSGO-CCTG). Surg. Today 2018, 48, 66–72. [Google Scholar] [CrossRef]
- Okuno, K.; Aoyama, T.; Oba, K.; Yokoyama, N.; Matsuhashi, N.; Kunieda, K.; Nishimura, Y.; Akamatsu, H.; Kobatake, T.; Morita, S.; et al. Randomized phase III trial comparing surgery alone to UFT+PSK for stage II rectal cancer (JFMC38 trial). Cancer Chemother. Pharmacol. 2018, 81, 65–71. [Google Scholar] [CrossRef] [Green Version]
- Chay, W.Y.; Tham, C.K.; Toh, H.C.; Lim, H.Y.; Kiat, T.; Lim, C.; Wang, W.; Choo, S. Coriolus versicolor (Yunzhi) use as therapy in advanced hepatocellular carcinoma patients with poor liver function or who are unfit for standard therapy. J. Altern. Complement. Med. 2017, 23, 648–652. [Google Scholar] [CrossRef]
- Torkelson, C.; Sweet, E.; Martzen, M.R.; Sasagawa, M.; Wenner, C.A.; Gay, J.; Putiri, A.; Standish, L.G. Phase 1 clinical trial of Trametes versicolor in women with breast cancer. ISRN Oncol. 2012, 2012. [Google Scholar] [CrossRef] [Green Version]
- Janardhanan, K.K.; Ravikumar, K.S.; Karuppayil, S.M. Medicinal mushroom bioactives: Potential sources for anti-cancer drug development. Int. J. App. Pharm. 2020, 12, 40–45. [Google Scholar] [CrossRef]
- Gao, Y.; Dai, X.; Chen, G.; Ye, J.; Zhou, S. A randomized, placebo-controlled, multicenter study of Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetideae) polysaccharides (Ganopoly®) in patients with advanced lung cancer. Int. J. Med. Mushrooms 2003, 5, 369–382. [Google Scholar] [CrossRef]
- Gao, Y.; Zhou, S.; Yang, W.; Huang, M.; Dai, X. Effects of Ganopoly® (A Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol. Invest. 2003, 32, 201–215. [Google Scholar] [CrossRef] [PubMed]
- Oka, S.; Tanaka, S.; Yoshida, S.; Himaya, T.; Ueno, Y.; Ito, M.; Kitadai, Y.; Yoshihara, M.; Chayama, K. A water-soluble extract from culture medium of Ganoderma lucidum mycelia suppresses the development of colorectal adenomas. Hiroshima J. Med. Sci. 2010, 59, 1–6. [Google Scholar] [PubMed]
- Tanaka, A.; Nishimura, M.; Sato, Y.; Sato, H.; Nishihira, J. Enhancement of the Th1-phenotype immune system by the intake of Oyster mushroom (Tamogitake) extract in a double-blind, placebocontrolled study. J. Tradit. Complement. Med. 2015, 6, 424–430. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Twardowski, P.; Kanaya, N.; Frankel, P.; Synold, T.; Ruel, C.; Pal, S.K.; Junqueira, M.; Prajapati, M.; Nguyen, T.; Tryon, P.; et al. A phase I trial of mushroom powder in patients with biochemically recurrent prostate cancer: Roles of cytokines and myeloid-derived suppressor cells (MDSCs) for Agaricus bisporus induced PSA responses. Cancer 2015, 121, 2942–2950. [Google Scholar] [CrossRef] [Green Version]
- Costa Fortes, R.; Lacorte Recôva, V.; Lima Melo, A.; Carvalho Garbi Novaes, M.R. Life quality of postsurgical patients with colorectal cancer after supplemented diet with agaricus sylvaticus fungus. Nutr. Hosp. 2010, 25, 586–596. [Google Scholar] [CrossRef]
- Costa Fortes, R.; Carvalho Garbi Novaes, M.R. The effects of Agaricus sylvaticus fungi dietary supplementation on the metabolism and blood pressure of patients with colorectal cancer during post surgical phase. Nutr. Hosp. 2011, 26, 176–186. [Google Scholar]
- Valadares, F.; Carvalho Garbi Novaes, M.R.; Cañete, R. Effect of Agaricus sylvaticus supplementation on nutritional status and adverse events of chemotherapy of breast cancer: A randomized, placebo-controlled, double-blind clinical trial. Indian J. Pharmacol. 2013, 45, 217–222. [Google Scholar] [CrossRef]
- Tsai, M.; Hung, Y.; Chen, Y.; Chen, Y.; Huang, Y.; Kao, C.; Su, Y.; Chiu, H.E.; Rau, K. A preliminary randomised controlled study of short-term Antrodia cinnamomea treatment combined with chemotherapy for patients with advanced cancer. BMC Complement. Altern. Med. 2016, 16, 322. [Google Scholar] [CrossRef] [Green Version]
- Ina, K.; Furuta, R.; Kataoka, T.; Kayukawa, S.; Yoshida, T.; Miwa, T.; Yamamura, Y.; Takeuchi, Y. Lentinan prolonged survival in patients with gastric cancer receiving S-1-based chemotherapy. World J. Clin. Oncol. 2011, 2, 339–343. [Google Scholar] [CrossRef]
- Ma, J. Efficacy of lentinan combined with NP regimen in treatment of patients with advanced nonsmall-cell lung cancer and its effect on immunologic function. Zhongguo Fei Ai Za Zhi (Chinese Journal of Lung cancer) 2014. Corpus ID: 75303359. [Google Scholar]
- Wang, X.; Wang, Y.; Zhou, Q.; Peng, M.; Zhang, J.; Chen, M.; Ma, L.; Xie, G. Immunomodulatory effect of Lentinan on aberrant T subsets and cytokines profile in non-small cell lung cancer patients. Pathol. Oncol. Res. 2020, 26, 499–505. [Google Scholar] [CrossRef] [PubMed]
- Sukhnikhom, W.; Lertkhachonsuk, R.; Manchana, T. The effects of active Hexose correlated compound (AHCC) on levels of CD4+ and CD8+ in patients with epithelial ovarian cancer or peritoneal cancer receiving platinum based chemotherapy. Asian Pac. J. Cancer Prev. 2017, 18, 633–638. [Google Scholar] [CrossRef]
- Ito, T.; Urushima, H.; Sakaue, M.; Yukawa, S.; Honda, H.; Hirai, K.; Igura, T.; Hayashi, N.; Maeda, K.; Kitagawa, T.; et al. Reduction of adverse effects by a mushroom product, active hexose correlated compound (AHCC) in patients with advanced cancer during chemotherapy--the significance of the levels of HHV-6 DNA in saliva as a surrogate biomarker during chemotherapy. Nutr. Cancer. 2014, 66, 377–382. [Google Scholar] [CrossRef] [PubMed]
- Del Buono, A.; Bonucci, M.; Pugliese, S.; D’Orta, A.; Fioranelli, M. Polysaccharide from lentinus edodes for integrative cancer treatment: Immunomodulatory effects on lymphocyte population. WCRJ 2016, 3, e652. [Google Scholar]
- D’Orta, A.; Del Buono, A.; De Monaco, A.; Zhiqiang, P.; Licito, A.; Di Martino, S. Management and treatment of sarcopenia in fifty patients receiving chemotherapy with AHCC (active hexose correlated compound). WCRJ 2018, 5, e1089. [Google Scholar]
- Hsu, C.; Liao, Y.; Lin, S.; Hwang, K.; Chou, P. The mushroom Agaricus Blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: A randomized, double-blinded, and placebo-controlled clinical trial. J. Altern. Complement. Med. 2007, 13, 97–102. [Google Scholar] [CrossRef] [Green Version]
- Sun, L.; Niu, Z. A mushroom diet reduced the risk of pregnancy-induced hypertension and macrosomia: A randomized clinical trial. Food Nutr. Res. 2020, 64, 4451. [Google Scholar] [CrossRef]
- Klupp, N.L.; Kiat, H.; Bensoussan, A.; Steiner, G.Z.; Chang, D.H. A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome. Sci. Rep. 2016, 6, 29540. [Google Scholar] [CrossRef]
- Khatun, K.; Mahtab, H.; Khanam, P.A.; Sayeed, M.A.; Khan, K.A. Oyster mushroom reduced blood glucose and cholesterol in diabetic subjects. Mymensingh Med. J. 2007, 16, 94–99. [Google Scholar] [CrossRef]
- Kajaba, I.; Simoncic, R.; Frecerova, K.; Belay, G. Clinical studies on the hypolipidemic and antioxidant effects of selected natural substances. Bratisl. Lek. Listy 2008, 109, 267–272. [Google Scholar]
- Schneider, I.; Kressel, G.; Meyer, A.; Krings, U.; Berger, R.G.; Hahn, A. Lipid lowering effects of oyster mushroom (Pleurotus ostreatus) in humans. J. Funct. Foods 2011, 3, 17–24. [Google Scholar] [CrossRef]
- Choudhury, M.B.K.; Rahman, T.; Kakon, A.J.; Hoque, N.; Akhtaruzzaman, M.; Begum, M.M.; Choudhury, M.S.K.; Hossain, M.S. Effects of Pleurotus ostreatus on blood pressure and glycemic status of hypertensive diabetic male volunteers. Bangladesh J. Med. Biochem. 2013, 6, 5–10. [Google Scholar] [CrossRef] [Green Version]
- Choudhury, M.B.K.; Hossain, M.S.; Hossain, M.M.; Kakon, A.J.; Choudhury, M.A.K.; Ahmed, N.U.; Rahman, T. Pleurotus ostreatus improves lipid profile of obese hypertensive non-diabetic males. Bangladesh J. Mushroom. 2013, 7, 37–44. [Google Scholar]
- Sayeed, M.; Banu, A.; Khatun, K.; Khanam, P.A.; Begum, T.; Mahtab, H.; Haq, J.A. Effect of edible mushroom (Pleurotus ostreatus) on type-2 diabetics. Ibrahim Med. Coll. J. 2014, 8, 6–11. [Google Scholar] [CrossRef] [Green Version]
- Jayasuriya, W.J.A.B.N.; Wanigatunge, C.A.; Fernando, G.H.; Abeytunga, D.T.U.; Suresh, T.S. Hypoglycaemic activity of culinary Pleurotus ostreatus and P. cystidiosus mushrooms in healthy volunteers and type 2 diabetic patients on diet control and the possible mechanisms of action. Phytother. Res. 2015, 29, 303–309. [Google Scholar] [CrossRef] [PubMed]
- Tang, W.; Gao, Y.; Chen, G.; Gao, H.; Dai, X.; Ye, J.; Chan, E.; Huang, M.; Zhou, S. A randomized, double-blind and placebo-controlled study of a Ganoderma lucidum polysaccharide extract in neurasthenia. J. Med. Food. 2005, 8, 53–58. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mori, K.; Inatomi, S.; Ouchi, K.; Azumi, Y.; Tuchida, T. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: A double-blind placebo-controlled clinical trial. Phytother. Res. 2009, 23, 367–372. [Google Scholar] [CrossRef]
- Li, I.; Chang, H.; Lin, C.; Chen, W.; Lu, T.; Lee, L.; Chen, Y.; Chen, Y.-P.; Chen, C.; Lin, D.P. Prevention of early Alzheimer’s disease by erinacine A-enriched Hericium erinaceus mycelia pilot double-blind placebo-controlled study. Front. Aging Neurosci. 2020, 12, 155. [Google Scholar] [CrossRef]
- Nagano, M.; Shimizu, K.; Kondo, R.; Hayashi, C.; Sato, D.; Kitagawa, K.; Ohkuni, K. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed. Res. 2010, 31, 231–237. [Google Scholar] [CrossRef] [Green Version]
- Inanaga, K. Marked improvement of neurocognitive impairement after treatment with compounds from Hericium erinaceum: A case study of recurrent depressive disorder. Pers. Med. Universe 2014, 3, 46–48. [Google Scholar] [CrossRef]
- Vigna, L.; Morelli, F.; Agnelli, G.M.; Napolitano, F.; Ratto, D.; Occhinegro, A.; Di Iorio, C.; Savino, E.; Girometta, C.; Brandalise, F.; et al. Hericium erinaceus improves mood and sleep disorders inpatients affected by overweight or obesity: Could circulating pro-BDNF and BDNF be potential biomarkers? Evid. Based Complementary Altern. Med. 2019, 2019. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Palomares, M.R.; Rodriguez, J.; Phung, S.; Stanczyc, F.Z.; Lacey, S.F.; Synolds, S.D.; Denison, T.W.; Frankel, P.H.; Chen, S. A dose-finding clinical trial of mushroom powder in postmenopausal breast cancer survivors for secondary breast cancer prevention. J. Clin. Oncol. 2011, 29. [Google Scholar] [CrossRef]
- Hess, J.; Wang, Q.; Gould, T.; Slavin, J. Impact of Agaricus bisporus mushroom consumption on gut health markers in healthy adults. Nutrients 2018, 10, 1402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jesenak, M.; Majtan, J.; Rennerova, Z.; Kyselovic, J.; Banovcin, P.; Hrubisko, M. Immunomodulatory effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. Int. Immunopharmacol. 2013, 15, 395–399. [Google Scholar] [CrossRef]
- Urbancikova, I.; Hudackova, D.; Majtan, J.; Rennerova, Z.; Banovcin, P.; Jesenak, M. Efficacy of Pleuran (β-Glucan from Pleurotus ostreatus) in the management of Herpes Simplex Virus Type 1 infection. Evid. Based Complement. Alternat. Med. 2020, 2020, 8562309. [Google Scholar] [CrossRef] [Green Version]
- Okamura, H.; Anno, N.; Tsuda, A.; Inokuchi, T.; Uchimura, N.; Inanaga, K. The effects of Hericium erinaceum (Amyloban® 3399)on sleep quality and subjective well-being among female undergraduate students: A pilot study. Pers. Med. Universe 2015, 4, 76–78. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Venturella, G.; Ferraro, V.; Cirlincione, F.; Gargano, M.L. Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials. Int. J. Mol. Sci. 2021, 22, 634. https://doi.org/10.3390/ijms22020634
Venturella G, Ferraro V, Cirlincione F, Gargano ML. Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials. International Journal of Molecular Sciences. 2021; 22(2):634. https://doi.org/10.3390/ijms22020634
Chicago/Turabian StyleVenturella, Giuseppe, Valeria Ferraro, Fortunato Cirlincione, and Maria Letizia Gargano. 2021. "Medicinal Mushrooms: Bioactive Compounds, Use, and Clinical Trials" International Journal of Molecular Sciences 22, no. 2: 634. https://doi.org/10.3390/ijms22020634