A Mechanistic Review on Medicinal Mushrooms-Derived Bioactive Compounds: Potential Mycotherapy Candidates for Alleviating Neurological Disorders

Abstract

According to the World Health Organization, neurological and neurodegenerative diseases are highly debilitating and pose the greatest threats to public health. Diseases of the nervous system are caused by a particular pathological process that negatively affects the central and peripheral nervous systems. These diseases also lead to the loss of neuronal cell function, which causes alterations in the nervous system structure, resulting in the degeneration or death of nerve cells throughout the body. This causes problems with movement (ataxia) and mental dysfunction (dementia), both of which are commonly observed symptoms in Alzheimerʼs disease, Parkinsonʼs disease, Huntingtonʼs disease, and multiple sclerosis. Medicinal mushrooms are higher fungi with nutraceutical properties and are low in calories and fat. They are also a rich source of nutrients and bioactive compounds such as carbohydrates, proteins, fibers, and vitamins that have been used in the treatment of many ailments. Medicinal mushrooms such as Pleurotus giganteus, Ganoderma lucidium, and Hericium erinaceus are commonly produced worldwide for use as health supplements and medicine. Medicinal mushrooms and their extracts have a large number of bioactive compounds, such as polysaccharide β-glucan, or polysaccharide-protein complexes, like lectins, lactones, terpenoids, alkaloids, antibiotics, and metal-chelating agents. This review will focus on the role of the medicinal properties of different medicinal mushrooms that contain bioactive compounds with a protective effect against neuronal dysfunction. This information will facilitate the development of drugs against neurodegenerative diseases.

Key words

medicinal mushrooms - Cyathus - Sarcodon - Hericium - Antrodia - Ganoderma - Pleurotus - bioactive compounds - neurological disorder - neurodegenerative diseases

Publikationsverlauf

Eingereicht: 08. August 2019

Angenommen nach Revision: 13. Mai 2020

Artikel online veröffentlicht:
14. Juli 2020

• References

• 1 Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech 2017; 10: 499-502
• 2 Gandhi J, Antonelli AC, Afridi A, Vatsia S, Joshi G, Romanov V, Murray IVJ, Khan SA. Protein misfolding and aggregation in neurodegenerative diseases: a review of pathogeneses, novel detection strategies, and potential therapeutics. Rev Neurosci 2019; 30: 339-358
• 3 Ganguly U, Chakrabarti SS, Kaur U, Mukherjee A, Chakrabarti S. Alpha-synuclein, proteotoxicity and Parkinsonʼs disease: search for neuroprotective therapy. Curr Neuropharmacol 2018; 16: 1086-1097
• 4 Krainc D. Clearance of mutant proteins as a therapeutic target in neurodegenerative diseases. Arch Neurol 2010; 67: 388-392
• 5 Sleegers K, Lambert JC, Bertram L, Cruts M, Amouyel P, Van Broeckhoven C. The pursuit of susceptibility genes for Alzheimerʼs disease: progress and prospects. Trends Genet 2010; 26: 84-93
• 6 Gandhi S, Wood NW. Genome-wide association studies: the key to unlocking neurodegeneration?. Nat Neurosci 2010; 13: 789-794
• 7 Noorbakhsh F, Overall CM, Power C. Deciphering complex mechanisms in neurodegenerative diseases: the advent of systems biology. Trends Neurosci 2009; 32: 88-100
• 8 Lei XG, Zhu JH, Cheng WH, Bao Y, Ho YS, Reddi AR, Holmgren A, Arnér ES. Paradoxical roles of antioxidant enzymes: basic mechanisms and health implications. Physiol Rev 2016; 96: 307-364
• 9 Mattson MP, Arumugam TV. Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metab 2018; 27: 1176-1199
• 10 Von Bernhardi R, Eugenín-von Bernhardi L, Eugenín J. Microglial cell dysregulation in brain aging and neurodegeneration. Front Aging Neurosci 2015; 7: 124
• 11 Schwartz M, Deczkowska A. Neurological disease as a failure of brain-immune crosstalk: the multiple faces of neuroinflammation. Trends Immunol 2016; 37: 668-679
• 12 Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimerʼs disease: systematic review and meta-analysis of observational studies. BMJ 2003; 327: 128
• 13 McGeer PL, McGeer EG. NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging 2007; 28: 639-647
• 14 Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008; 70: 1672-1677
• 15 Wang J, Tan L, Wang HF, Tan CC, Meng XF, Wang C, Tang SW, Yu JT. Anti-inflammatory drugs and risk of Alzheimerʼs disease: an updated systematic review and meta-analysis. J Alzheimers Dis 2015; 44: 385-396
• 16 Cooper DJ, Zunino G, Bixby JL, Lemmon VP. Phenotypic screening with primary neurons to identify drug targets for regeneration and degeneration. Mol Cell Neurosci 2017; 80: 161-169
• 17 Durães F, Pinto M, Sousa E. Old drugs as new treatments for neurodegenerative diseases. Pharmaceuticals (Basel) 2018; 11: 44
• 18 Hawksworth DL, Lücking R. Fungal diversity revisited: 2.2 to 3.8 million species. Microbiol Spectr 2017; 5: 1-2
• 19 De Silva DD, Rapior S, Sudraman E, Stadler M, Xu JC, Alias SA, Hyde KD. Bioactive metabolites from macrofungi: ethnopharmacology, biological activities and chemistry. Fungal Div 2013; 62: 1-40
• 20 De Silva DD, Rapior S, Hyde KD, Bahkali AH. Medicinal mushroom in prevention and control of diabetes mellitus. Fungal Div 2012; 56: 1-29
• 21 Valverde ME, Pérez TH, López OP. Edible mushrooms: improving human health and promoting quality life. Int J Microbiol 2015; 2015: 376387
• 22 Phan CW, David P, Sabratnam V. Edible and medicinal mushrooms: emerging brain food for the mitigation of neurodegenerative diseases. J Medicinal Food 2017; 20: 1-10
• 23 Kirk PM. Species Fungorum (version 26th August 2015). Species 2000 & ITIS Catalogue of Life. Available at (Accessed March 1, 2020): http://www.speciesfungorum.org
• 24 Larsson KH, Svantesson S, Miscevic D, Kõljalg U, Larsson E. Reassessment of the generic limits for Hydnellum and Sarcodon (Thelephorales, Basidiomycota). MycoKeys 2019; 54: 31-47
• 25 Marcotullio MC, Pagiott R, Maltese F, Obara Y, Hoshino T, Nakahata N, Curini M. Neurite outgrowth activity of cyathane diterpenes from Sarcodon cyrneus, cyrneines A and B. Planta Med 2006; 72: 819-823
• 26 Marcotullio MC, Pagiotti R, Maltese F, Oball-Mond Mwankie GN, Hoshino T, Obara Y, Nakahata N. Cyathane diterpenes from Sarcodon cyrneus and evaluation of their activities of neuritegenesis and nerve growth factor production. Bioorg Med Chem 2007; 15: 2878-2882
• 27 Marcutullio MC, Pagiotti R, Campagna V, Maltese F, Fardella G, Altinier G, Tubaro A. Glaucopine C, a new diterpene from fruiting bodies of Sarcodon glaucopus . Nat Prod Res 2006; 20: 917-921
• 28 Obara Y, Nakahata N, Kita T, Takaya Y, Kobayashi H, Hosoi S, Kiuchi F, Ohta T, Oshima Y, Ohizumi Y. Stimulation of neurotrophic factor secretion from 1321N1 human astrocytoma cells by novel diterpenoids, scabronines A and G. Eur J Pharmacol 1999; 370: 79-84
• 29 Ohta T, Kita T, Kobayashi N, Obara Y, Nakahata N, Ohizumi Y, Takaya Y, Oshima Y. Scabronine A, a novel diterpenoid having potent inductive activity of the nerve growth factor synthesis, isolated from the mushroom, Sarcodon scabrosus . Tetrahedron Lett 1998; 39: 6229-6232
• 30 Kita T, Takaya Y, Oshima Y, Ohta T, Aizawa K, Hirano T, Inakuma T. Scabronines B, C, D, E and F, novel diterpenoids showing stimulating activity of nerve growth factor-synthesis, from the mushroom Sarcodon scabrosus . Tetrahedron 1998; 54: 11877-11886
• 31 Shi XW, Liu L, Gao JM, Zhang AL. Cyathane diterpenes from Chinese mushroom Sarcodon scabrosus and their neurite outgrowth promoting activity. Eur J Med Chem 2011; 46: 3112-3117
• 32 Liu L, Shi XW, Zong SC, Tang JJ, Gao JM. Scabronine M, a novel inhibitor of NGF induced neurite outgrowth from PC12 cells from the fungus Sarcodon scabrosus . Bioorg Med Chem Lett 2012; 22: 2401-2406
• 33 Obara Y, Kobayashi H, Ohta T, Ohizumi Y, Nakahata N. Scabronine G methyl ester enhances secretion of neurotrophic factors mediated by an activation of protein kinase C-ζ. Mol Pharma 2001; 59: 1287-1297
• 34 Obara Y, Hoshino T, Marcutollio MC, Pagiotti R, Nakahata N. A novel cyathane diterpene, cyrneine A, induces neurite outgrowth in a Rac1-dependent mechanism in PC12 cells. Life Sci 2007; 80: 1669-1677
• 35 Moore DL, Goldberg JL. Multiple transcription factor families regulate axon growth and regeneration. Dev Neurobiol 2011; 71: 1186-1211
• 36 Cingolani L, Goda Y. Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy. Nat Rev Neurosci 2008; 9: 344-356
• 37 Song TY, Lin HC, Chen CL, Wu JH, Liao JW, Hu ML. Ergothioneine and melatonin attenuate oxidative stress and protect against learning and memory deficits in C57BL/6J mice treated with D-galactose. Free Radic Res 2014; 48: 1049-1060
• 38 Tang HY, Yin X, Zhang CC, Jia Q, Gao JM. Structure diversity, synthesis, and biological activity of cyathane diterpenoids in higher fungi. Curr Med Chem 2015; 22: 2375-2391
• 39 Bai R, Zhang CC, Yin X, Wei J, Gao JM. Striatoids A–F, cyathane diterpenoids with neurotrophic activity from cultures of the fungus Cyathus striatus . J Nat Prod 2015; 78: 783-788
• 40 Kou RW, Du ST, Li YX, Yan XT, Zhang Q, Cao CY, Yin X, Gao JM. Cyathane diterpenoids and drimane sesquiterpenoids with neurotrophic activity from cultures of the fungus Cyathus africanus . J Antbiot (Tokyo) 2019; 72: 15-21
• 41 Tang D, Xu YZ, Wang WW, Yang Z, Liu B, Stadler M, Liu LL, Gao JM. Cyathane diterpenes from cultures of the birdʼs nest fungus Cyathus hookeri and their neurotrophic and anti-neuroinflammatory activities. J Nat Prod 2019; 82: 1599-1608
• 42 Ganeshan N, Baskaran R, Velmurugan BK, Thanh NC. Antrodia cinnamomea–an updated minireview of its bioactive components and biological activity. J Food Biochem 2019; 43: e12936
• 43 Wang C, Zhang W, Wong JH, Ng T, Ye X. Diversity of potentially exploitable pharmacological activities of the highly prized edible medicinal fungus Antrodia camphorate . Appl Microbiol Biotechnol 2019; 103: 7843-7867
• 44 Lee TH, Lee CK, Tsou WL, Liu SY, Kuo MT, Wen WC. A new cytotoxic agent from solid-state fermented mycelium of Antrodia camphorata . Planta Med 2007; 73: 1412-1415
• 45 Chen MC, Cho TY, Kou YH, Lee TH. Meroterpenoids from medicinal fungus Antrodia cinnamomea . J Nat Prod 2007; 80: 2439-2446
• 46 Chang WH, Chen MC, Cheng IH. Antroquinonol lowers brains amyloid-β levels and improves spatial learning and memory in transgenic mice mouse model of Alzheimerʼs diseases. Sci Rep 2015; 5: 15067
• 47 Karkkainen V, Pomeshchik Y, Savchenko E, Dhungana H, Kurronen A, Lehtonen S, Naumenko N, Tavi P, Levonen AL, Yamamoto M, Malm T, Magga J, Kanninen KM, Koistinaho J. Nfr2 regulates neurogenesis and protects neural progenitor cells against Aβ-toxicity. Stem Cell 2014; 32: 1904-1916
• 48 Lu MK, Cheng JJ, Lai WL, Lin YR, Huang NK. Adenosine as an active component of Antrodia cinnamomea that prevents rat PC12 cells from serum deprivation-induced apoptosis through the activation of adenosine A2A receptors. Life Sci 2006; 79: 252-258
• 49 Domenici MR, Ferrante A, Martire A, Chiodi V, Pepponi R, Tebano MT, Popoli P. Adenosine A2A receptor as potential therapeutic target in neuropsychiatric disorders. Pharmacol Res 2019; 147: 104338
• 50 Liu DZ, Liang HJ, Chen CH, Su CH, Lee TH, Huang CT, Hou WC, Lin SY, Zhong WB, Lin PJ, Hung LF, Liang YC. Comparative anti-inflammatory characterization of wild fruiting body, liquid-state fermentation, and solid-state culture of Taiwanofungus camphoratus in microglia and the mechanism of its action. J Ethnopharmacol 2007; 113: 45-53
• 51 Chen-Roetling J, Lu X, Regan RF. Targeting heme oxygenase after intracerebral hemorrhage. Ther Targets Neurol Dis 2015; 2: 474
• 52 Phan CW, Wong WL, David P, Naidu M, Sabaratnam V. Pleurotus giganteus (Berk) Karunarathna and KD Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells. BMC Complem Altern Med 2012; 12: 10
• 53 Phan CW, David P, Wong KH, Naidu M, Sabaratnam V. Uridine from Pleurotus giganteus and its neurite outgrowth stimulatory effects with underlying mechanism. PLoS One 2015; 10: e0143004
• 54 Chang YS, Lee SS. Utilisation of macrofungi species in Malaysia. Fungal Div 2004; 15: 15-22
• 55 Moroney S. Chemical Constituents in the fruiting Bodies of Pleurotus giganteus (Berk.) Karunarathna & K. D. Hyde Extracts by GC-MS and LC-MS/MS [PhD thesis]. Kuala Lumpur: University of Malaya; 2012
• 56 Cansev M. Uridine and cytidine in the brain: their transport and utilization. Brain Res Rev 2006; 52: 389-397
• 57 Ishimoto T, Nakamichi N, Hosotani H, Masuo Y, Sugiura T, Kato Y. Organic cation transporter-mediated ergothioneine uptake in mouse neural progenitor cells suppresses proliferation and promotes differentiation into neurons. PLoS One 2014; 9: e89434
• 58 Song TY, Lin HC, Chen CL, Wu JH, Liao JW, Hu ML. Ergothioneine and melatonin attenuate oxidative stress and protect against learning and memory deficits in C57BL/6J mice treated with D-galactose. Free Radic Res 2014; 48: 1049-1060
• 59 Yang NC, Lin HC, Wu JH, Ou HC, Chai YC, Tseng CY, Liao JW, Song TY. Ergothioneine protects against neuronal injury induced by β-amyloid in mice. Food Chem Toxicol 2012; 50: 3902-3911
• 60 Nakamichi N, Nakayama K, Ishimoto T, Masuo Y, Wakayama T, Sekiguchi H, Sutoh K, Usumi K, Iseki S, Kato Y. Food-derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice. Brain Behav 2016; 6: e00477
• 61 Cilerdzic JL, Sofrenic IV, Tesevic VV, Brceski ID, Duletic-Lausevic SN, Vukojevic JB, Stajic MM. Neuroprotective potential and chemical profile of alternatively cultivated Ganoderma lucidum Basidiocarps. Chem Biodivers 2018; 15: e1800036
• 62 Wang J, Cao B, Zhao H, Feng J. Emerging role of Ganodrma lucidum in anti-aging. Aging Dis 2017; 8: 691-707
• 63 Wang GH, Wang LH, Wang C, Qin LH. Spore powder of Ganoderma lucidum for the treatment of Alzheimer disease. Medicine (Baltimore) 2018; 97: e0636
• 64 Seow SLS, Naidu M, David P, Wong KH, Sabratnam V. Potentiation of neuritogenic activity of medicinal mushrooms in rat pheochoromocytoma cells. BMC Complement Altern Med 2013; 13: 157
• 65 Zhang XQ, Ip FC, Zhang DM, Chen LX, Zhang W, Li YL, Ip NY, Ye WC. Triterpenoids with neurotrophic activity from Ganoderma lucidum . Nat Prod Res 2011; 25: 1607-1613
• 66 Weng Y, Xiang L, Matsuura A, Zhang Y, Huang Q, Qi J. Ganodermasides A and B, two novel anti-aging ergosterols from spores of a medicinal mushroom Ganoderma lucidum on yeast via UTH1 gene. Bioorg Med Chem 2010; 18: 999-1002
• 67 Méndez-Armenta M, Nava-Ruíz C, Juárez-Rebollar D, Rodríguez-Martínez E, Gómez PY. Oxidative stress associated with neuronal apoptosis in experimental models of epilepsy. Oxid Med Cell Longev 2014; 2014: 293689
• 68 Liu JX, Liu XG, Wang L, Wu F, Yang ZW. Neuroprotective effects of ganoderic acid extract against epilepsy in primary hippocampal neurons. Res Opin Anim Vet Sci 2013; 13: 420-425
• 69 Jiang ZM, Qiu HB, Wang SQ, Guo J, Yang ZW, Zhou SB. Ganoderic acid A potentiates the antioxidant effect and protection of mitochondrial membranes and reduces the apoptosis rate in primary hippocampal neurons in magnesium free medium. Pharmazie 2018; 73: 87-91
• 70 Wang C, Liu X, Lian C, Ke J, Liu J. Triterpenes and aromatic Meroterpenoids with antioxidant activity and neuroprotective effects from Ganoderma lucidum . Molecules 2019; 24: E4353
• 71 Lu SY, Peng XR, Dong JR, Yan H, Kong QH, Shi QQ, Li DS, Zhou L, Li ZR, Qiu MH. Aromatic constituents from Ganoderma lucidum and their neuroprotective and anti-inflammatory activities. Fitoterapia 2019; 134: 58-64
• 72 Boyle MP, Brewer JA, Funatsu M, Wozniak DF, Tsien JZ, Izumi Y, Muglia LJ. Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. Proc Natl Acad Sci U S A 2005; 102: 473-478
• 73 Kunugi H, Hori H, Adachi N, Numakawa T. Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression. Psychiatry Clin Neurosci 2010; 64: 447-459
• 74 Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 2011; 476: 458-461
• 75 Thongbai B, Rapior S, Hyde KD, Wittstein K, Stadler M. Hericium erinaceus, an amazing medicinal mushroom. Mycol Progr 2015; 14: 91
• 76 Chong PS, Fung ML, Wong KH, Lim LW. Therapeutic potential of Hericium erinaceus for depressive disorder. Int J Mol Sci 2019; 21: E163
• 77 Lu QQ, Tian JM, Wei J, Gao JM. Bioactive metabolites from the mycelia of the basidiomycete Hericium erinaceum . Nat Prod Res 2014; 28: 1288-1292
• 78 Lai PL, Naidu M, Sabaratnam V, Wong KH, David RP, Kuppusamy UR, Abdullah N, Malek SNA. Neurotrophic properties of the Lionʼs mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. Int J Med Mushrooms 2013; 15: 539-554
• 79 Friedman M. Chemistry nutrition and health promoting properties of Hericeum erinaceus (Lionʼs mane) mushroom fruiting bodies and mycelia and their bioactive compound. J Agric Food Chem 2015; 63: 7108-7123
• 80 Kawagishi H, Ando M, Sakamoto H, Yoshida S, Ojima F, Ishigurob Y, Ukai N, Furukawa S. Hericenones C, D, and E, stimulators of nerve growth factor synthesis, from the mushroom Hericium erinaceus . Tetrahedron Lett 1991; 32: 4561-4564
• 81 Kawagishi H, Shimada A, Shirai R, Okamoto K. Erinacines A, B, and C, strong stimulator of nerve growth factor (NGF)-synthesis from the mycelia of Hericium erinceum . Tetrahedron Lett 1994; 35: 1569-1572
• 82 Kawagishi H, Shimada A, Shizuki K, Mori H, Okamoto K, Sakamoto H, Furukawa S, Ojima F. Erinacine D, a stimulator of NGF-synthesis from the mycelia of Hericium erinaceus . Heterocycle Commun 1996; 2: 51-54
• 83 Lee EW, Shizuki K, Hosokawa S, Suzuki M, Suganuma H, Inakuma T, Li J, Ohnishi-Kameyama M, Nagata T, Furukawa S, Kawagishi H. Two novel diterpenoids, erinacines H–I from the mycelia of Hericium erinaceum . Biosci Biotechnol Biochem 2000; 64: 2402-2405
• 84 Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Ischemia/Reperfusion. Compr Physiol 2017; 7: 113-170
• 85 Sano R, Reed JC. ER stress-induced cell death mechanism. Biochim Biophys Acta 2013; 1833: 3460-3470
• 86 Lee KF, Chen JH, Teng CC, Shen CH, Hsieh MC, Lu CC, Lee KC, Lee LY, Chen WP, Chen CC, Huang WS, Kuo HC. Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the Inhibition of iNOS/p38 MAPK and nitrotyrosine. Int J Mol Sci 2014; 15: 15073-15089
• 87 Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biol Pharm Bull 2008; 31: 1727-1732
• 88 Kenmoku H, Tanaka K, Okada K, Kato N, Sassa T. Erinacol (cyatha-3,12-dien-14beta-ol) and 11-O-acetylcyathin A3, new cyathane metabolites from an erinacine Q-producing Hericium erinaceum . Biosci Biotechnol Biochem 2004; 68: 1786-1789
• 89 Phan CW, Lee GS, Hong SL, Wong YT, Brkljača R, Urban S, Abd Malek SN, Sabaratnam V. Hericium erinaceus (Bull.: Fr) Pers. cultivated under tropical conditions: isolation of hericenones and demonstration of NGF-mediated neurite outgrowth in PC12 cells via MEK/ERK and PI3K-Akt signaling pathways. Food Funct 2014; 5: 3160-3169
• 90 Zhang CC, Cao CY, Kubo M, Harada K, Yan XT, Fukuyama Y, Gao JM. Chemical constituents from Hericium erinaceus promote neuronal survival and potentiate neurite outgrowth via the TrkA/Erk1/2 pathways. Int J Mol Sci 2017; 18: 1659
• 91 Carlstedt T. Approaches permitting and enhancing motoneuron regeneration after spinal cord, ventral root, plexus and peripheral nerve injuries. Curr Opin Neurol 2000; 13: 683-686
• 92 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
• 93 Diling C, Tiangiao Y, Jian Y, Chaoqun Z, Ou S, Yizhen X. Docking studies and biological evaluation of a potential β-secretase inhibitor of 3-hydroxyhericenone F from Hericium erinaceus . Front Pharmacol 2017; 8: 219
• 94 Kuo HC, Lu CC, Shen CH, Tung SY, Hsieh MC, Lee KC, Lee LY, Chen CC, Teng CC, Huang WS, Chen TC, Lee KF. 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
• 95 Speciale SG. MPTP: insights into parkinsonian neurodegeneration. Neurotoxicol Teratol 2002; 24: 607-620
• 96 Chiu CH, Chyau CC, Chen CC, Lee LY, Chen WP, Liu JL, Lin WH, Mong MC. Erinacine A-enriched Hericium erinaceus mycelium produces antidepressant-like effects through modulating BDNF/PI3K/Akt/GSK-3β signaling in mice. Int J Mol Sci 2018; 19: 341
• 97 Gill SK, Rieder MJ. Toxicity of a traditional Chinese medicine, Ganoderma lucidum, in children with cancer. Can J Clin Pharmacol 2008; 15: e275-e285
• 98 Wachtel-Galor S, Tomlinson B, Benzie IF. Ganoderma lucidum (“Lingzhi”), a Chinese medicinal mushroom: biomarker responses in a controlled human supplementation study. Br J Nutr 2004; 91: 263-926
• 99 Li EK, Tam LS, Wong CK, Li WC, Lam CW, Wachtel-Galor S, Benzie IF, Bao YX, Leung PC, Tomlinson B. Safety and efficacy of Ganoderma lucidum (lingzhi) and San Miao San supplementation in patients with rheumatoid arthritis: a double-blind, randomized, placebo-controlled pilot trial. Arthritis Rheum 2007; 57: 1143-1150
• 100 Dewi SC, Sargowo D, Widodo MA, Wihastuti TA, Heriansyah T, Hartanto MA, Ali T, Pambayun IDA, Bakhri SS, Gregorius DW, Aʼini NQ, Sahudi DP, Hantoko SH, Jaya JI, Octariny K, Ardhi AI. Ganoderma Lucidum subchronic toxicity on the liver as anti-oxidant and anti-inflammatory agent for cardiovascular disease. J Hypertens 2015; 33: e30