Neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, affect more than 55 million people worldwide and represent a growing public health challenge. Hericium erinaceus (Lion’s Mane mushroom) has attracted increasing attention due to its reported neuroprotective and antioxidant properties. This systematic review and limited meta-analysis evaluated current evidence regarding the effects of Hericium erinaceus on neurodegenerative disease-related outcomes. A systematic search of PubMed and Google Scholar was conducted following PRISMA guidelines for studies published between 2000 and 2026. From 1224 records identified, 23 studies met the inclusion criteria, comprising 12 animal studies, 8 in vitro studies and 3 human clinical trials. Study quality and risk of bias were assessed using SYRCLE and Cochrane tools. Across experimental models, Hericium erinaceus demonstrated consistent neuroprotective effects, which appeared to be mediated through multiple mechanisms, including enhancement of nerve growth factor and brain-derived neurotrophic factor signalling, activation of antioxidant defence pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2) signalling, suppression of NLRP3 inflammasome activity, reduction of oxidative stress, and attenuation of neuronal apoptosis. Limited human studies suggested potential benefits for cognitive function and mood. Quantitative synthesis supported the neuroprotective potential of Hericium erinaceus, with improvements in oxidative stress-related biomarkers observed across experimental studies. However, substantial heterogeneity and limited clinical evidence precluded definitive conclusions. Overall, Hericium erinaceus shows promising preclinical neuroprotective through multiple interconnected mechanisms, including antioxidant, anti-inflammatory, neurotrophic and anti-apoptotic pathways. However, its clinical efficacy in neurodegenerative disease remains unconfirmed.
- Open Access
- Review
Neuroprotective Effects of Hericium erinaceus: Evidence from Experimental and Clinical Studies—A Systematic Review and Limited Meta-Analysis
- Maya Gina Ninyo 1,
- Guoqiang Zhang 2,
- Shaobo Zhou 1,*
Author Information
Received: 19 Jul 2026 | Revised: 10 Sep 2026 | Accepted: 15 Sep 2026 | Published: 28 Sep 2026
Abstract
Keywords
Hericium erinaceus | Neuroprotection | Oxidative stress | Alzheimer’s disease | Parkinson’s disease | Nutraceuticals
References
- 1.
Cornford, N.; Charnley, M. Hericium erinaceus: A possible future therapeutic treatment for the prevention and delayed progression of Alzheimer’s disease?—A narrative review. Nutr. Res. Rev. 2025, 38, 613–627. https://doi.org/10.1017/s0954422425000058.
- 2.
Li, Y.; Lv, Z.; Dai, Y.; et al. The global, regional, and National burden of parkinson’s disease in 204 countries and territories, 1990–2021: A systematic analysis for the global burden of disease study 2021. BMC Public Health 2025, 25, 3047-. https://doi.org/10.1186/s12889-025-23492-8.
- 3.
Szućko-Kociuba, I.; Trzeciak-Ryczek, A.; Kupnicka, P.; et al. Neurotrophic and Neuroprotective Effects of Hericium erinaceus. Int. J. Mol. Sci. 2023, 24, 15960. https://doi.org/10.3390/ijms242115960.
- 4.
Contato, A.; Conte-Junior, C. Lion’s Mane Mushroom (Hericium erinaceus): A Neuroprotective Fungus with Antioxidant, Anti-Inflammatory, and Antimicrobial Potential—A Narrative Review. Nutrients 2025, 17, 1307. https://doi.org/10.3390/nu17081307.
- 5.
Zhou, S.; Hassan, H.; Guo, J.; et al. From gut to brain: Formulation and transporter-guided approaches to maximise rutin central nervous system delivery. Nutr. Neurosci. 2026, 29, 1022–1048. https://doi.org/10.1080/1028415x.2026.2617363.
- 6.
Yanshree; Yu, W.; Fung, M.; et al. The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease. Cells 2022, 11, 2284. https://doi.org/10.3390/cells11152284.
- 7.
Menon, A.; Jalal, A.; Arshad, Z.; et al. Benefits, side effects, and uses of Hericium erinaceus as a supplement: A systematic review. Front. Nutr. 2025, 12, 1641246. https://doi.org/10.3389/fnut.2025.1641246.
- 8.
Chong, P.S.; Fung, M.L.; Wong, K.H.; et al. Therapeutic Potential of Hericium erinaceus for Depressive Disorder. Int. J. Mol. Sci. 2020, 21, 163. https://doi.org/10.3390/ijms21010163.
- 9.
Othman, A.; Amen, Y.; Shimizu, K. Hericenones from Hericium erinaceus (Bull.) Pers.: A Scoping Review of Structural Diversity and Health Benefits. Chem. Biodivers. 2026, 23, e02560. https://doi.org/10.1002/cbdv.202502560.
- 10.
Wang, J.; Liu, H.; Wang, C.; et al. Recent Advances in Erinacine A: Preparation, Biological Activities, and Biosynthetic Pathway. Molecules 2026, 31, 219. https://doi.org/10.3390/molecules31020219.
- 11.
Spangenberg, E.; Moneypenny, A.; Bozzo, G.; et al. Unveiling the role of erinacines in the neuroprotective effects of Hericium erinaceus: A systematic review in preclinical models. Front. Pharmacol. 2025, 16, 1582081. https://doi.org/10.3389/fphar.2025.1582081.
- 12.
Ge, F.; Chen, Y.; Wang, B.; et al. Bioactive Polysaccharides from Hericium erinaceus: Extraction, Structure, Bioactivities, and Applications. Molecules 2025, 30, 1850. https://doi.org/10.3390/molecules30081850.
- 13.
Friedman, M. Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion’s Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds. J. Agric. Food Chem. 2015, 63, 7108–7123. https://doi.org/10.1021/acs.jafc.5b02914.
- 14.
Shirvani, M.; Nouri, F.; Sarihi, A.; et al. Neuroprotective Effects of Dehydroepiandrosterone and Hericium erinaceus in Scopolamine-induced Alzheimer’s Diseases-like Symptoms in Male Rats. Cell Biochem. Biophys. 2024, 82, 2853–2864. https://doi.org/10.1007/s12013-024-01400-y.
- 15.
Hsu, C.; Liao, E.; Chiang, W.; et al. Antioxidative Activities of Micronized Solid-State Cultivated Hericium erinaceus Rich in Erinacine A against MPTP-Induced Damages. Molecules 2023, 28, 3386. https://doi.org/10.3390/molecules28083386.
- 16.
Martínez-Mármol, R.; Chai, Y.; Conroy, J.N.; et al. Hericerin derivatives activates a pan-neurotrophic pathway in central hippocampal neurons converging to ERK1/2 signaling enhancing spatial memory. J. Neurochem. 2023, 165, 791–808. https://doi.org/10.1111/jnc.15767.
- 17.
Docherty, S.; Doughty, F.L.; Smith, E.F. The Acute and Chronic Effects of Lion’s Mane Mushroom Supplementation on Cognitive Function, Stress and Mood in Young Adults: A Double-Blind, Parallel Groups, Pilot Study. Nutrients 2023, 15, 4842. https://doi.org/10.3390/nu15224842.
- 18.
Suurmond, R.; van Rhee, H.; Hak, T. Introduction, comparison, and validation of Meta-Essentials: A free and simple tool for meta-analysis. Res. Synth. Methods 2017, 8, 537–553. https://doi.org/10.1002/jrsm.1260.
- 19.
D’Amico, R.; Trovato Salinaro, A.; Fusco, R.; et al. Hericium erinaceus and Coriolus versicolor Modulate Molecular and Biochemical Changes after Traumatic Brain Injury. Antioxidants 2021, 10, 898. https://doi.org/10.3390/antiox10060898.
- 20.
Cordaro, M.; Salinaro, A.T.; Siracusa, R.; et al. Key Mechanisms and Potential Implications of Hericium erinaceus in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease. Antioxidants 2021, 10, 1164. https://doi.org/10.3390/antiox10111664.
- 21.
Lee, K.F.; Hsieh, Y.Y.; Tung, S.Y.; et al. The Cerebral Protective Effect of Novel Erinacines from Hericium erinaceus Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways. Antioxidants 2024, 13, 371. https://doi.org/10.3390/antiox13030371.
- 22.
Lee, L.Y.; Chou, W.; Chen, W.P.; et al. Erinacine A-Enriched Hericium erinaceus Mycelium Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice. Nutrients 2021, 13, 3659. https://doi.org/10.3390/nu13103659.
- 23.
Roda, E.; Priori, E.C.; Ratto, D.; et al. Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging. Int. J. Mol. Sci. 2021, 22, 6379. https://doi.org/10.3390/ijms22126379.
- 24.
Roda, E.; De Luca, F.; Ratto, D.; et al. Cognitive Healthy Aging in Mice: Boosting Memory by an Ergothioneine-Rich Hericium erinaceus Primordium Extract. Biology 2023, 12, 196. https://doi.org/10.3390/biology12020196.
- 25.
Tsai, Y.C.; Lin, Y.C.; Huang, C.C.; et al. Hericium erinaceus Mycelium and Its Isolated Compound, Erinacine A, Ameliorate High-Fat High-Sucrose Diet-Induced Metabolic Dysfunction and Spatial Learning Deficits in Aging Mice. J. Med. Food 2019, 22, 469–478. https://doi.org/10.1089/jmf.2018.4288.
- 26.
Tsai, P.C.; Wu, Y.K.; Hu, J.H.; et al. Preclinical Bioavailability, Tissue Distribution, and Protein Binding Studies of Erinacine A, a Bioactive Compound from Hericium erinaceus Mycelia Using Validated LC-MS/MS Method. Molecules 2021, 26, 4510. https://doi.org/10.3390/molecules26154510.
- 27.
Chen, Y.Y.; Lin, T.W.; Li, I.C.; et al. A pilot pharmacokinetic and Metabolite identification study of Erinacine A in a Single landrace pig model. Heliyon 2024, 10, e37850. https://doi.org/10.1016/j.heliyon.2024.e37850.
- 28.
Lew, S.Y.; Lim, S.H.; Lim, L.W.; et al. Neuroprotective effects of Hericium erinaceus (Bull.: Fr.) Pers. against high-dose corticosterone-induced oxidative stress in PC-12 cells. BMC Complement. Med. Ther. 2020, 20, 340. https://doi.org/10.1186/s12906-020-03132-x.
- 29.
Zhang, C.C.; Yin, X.; Cao, C.Y.; et al. Chemical constituents from Hericium erinaceus and their ability to stimulate NGF-mediated neurite outgrowth on PC12 cells. Bioorganic Med. Chem. Lett. 2015, 25, 5078–5082. https://doi.org/10.1016/j.bmcl.2015.10.016.
- 30.
Tamrakar, S.; Wang, D.; Hiraki, E.; et al. Deacylated Derivative of Hericenone C Treated by Lipase Shows Enhanced Neuroprotective Properties Compared to Its Parent Compound. Molecules 2023, 28, 4549. https://doi.org/10.3390/molecules28114549.
- 31.
Lin, C.; Chen, Y.; Hsu, C.; et al. Erinacine S from Hericium erinaceus mycelium promotes neuronal regeneration by inducing neurosteroids accumulation. J. Food Drug Anal. 2023, 31, 32–54. https://doi.org/10.38212/2224-6614.3446.
- 32.
Wu, Y.L.; Sun, H.L.; Chang, J.C.; et al. Erinacine A-Enriched Hericium erinaceus Mycelium Ethanol Extract Lessens Cellular Damage in Cell and Drosophila Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation. Antioxidants 2024, 13, 1495. https://doi.org/10.3390/antiox13121495.
- 33.
Ghosh, S.; Nandi, S.; Banerjee, A.; et al. Prospecting medicinal properties of Lion’s mane mushroom. J. Food Biochem. 2021, 45, e13833. https://doi.org/10.1111/jfbc.13833.
- 34.
Qiao, Z.; Jia, X.; Wang, Y.; et al. Structural Analysis and Antioxidant Activity of Alkaline-Extracted Glucans from Hericium erinaceus. Foods 2024, 13, 2742. https://doi.org/10.3390/foods13172742.
- 35.
Amara, I.; Scuto, M.; Zappalà, A.; et al. Hericium Erinaceus Prevents DEHP-Induced Mitochondrial Dysfunction and Apoptosis in PC12 Cells. Int. J. Mol. Sci. 2020, 21, 2138. https://doi.org/10.3390/ijms21062138.
- 36.
Saitsu, Y.; Nishide, A.; Kikushima, K.; et al. Improvement of cognitive functions by oral intake of Hericium erinaceus. Biomed. Res. 2019, 40, 125–131. https://doi.org/10.2220/biomedres.40.125.
- 37.
Nagano, M.; Shimizu, K.; Kondo, R.; et al. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed. Res. 2010, 31, 231–237. https://doi.org/10.2220/biomedres.31.231.
- 38.
Cevik, C.; Ercan, A.M.; Or, M.E. Multimodal assessment of Hericium erinaceus and Valeriana officinalis for canine anxiety: Integrating EEG, neurochemical analysis, and behavioral surveys. J. Vet. Behav. 2025, 80, 57–68. https://doi.org/10.1016/j.jveb.2025.04.010.
- 39.
Çevik, Ç.; Kurt, B.O.; Bilgiç, B.; et al. The Chronic Metabolic Fingerprint of Canine Anxiety: Hair Trace Element Dyshomeostasis and the Dissociation of Behavioral Recovery via Hericium erinaceus. Biol. Trace Elem. Res. 2026, 204, 6233–6242. https://doi.org/10.1007/s12011-026-05107-4.
- 40.
Muhanna, M.; Lund, I.; Bromberg, M.; et al. ALSUntangled #73: Lion’s Mane. Amyotroph. Lateral Scler. Front. Degener. 2024, 25, 420–423. https://doi.org/10.1080/21678421.2023.2296557.
- 41.
Lai, P.L.; Naidu, M.; Sabaratnam, V.; et al. Neurotrophic Properties of the Lion’s Mane Medicinal Mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. Int. J. Med. Mushrooms 2013, 15, 539–554. https://doi.org/10.1615/intjmedmushr.v15.i6.30.
- 42.
Alsoufi, M.H.; AlGhamdi, N.; AlAhmady, N.F.; et al. Morphology, anticancer and neurological activities of Hericium erinaceus. Braz. J. Biol. 2025, 85, e296172. https://doi.org/10.1590/1519-6984.296172.
- 43.
Baker, J.F.; Newman, S.D. Theoretical Potential of Hericium Erinaceus Supplementation as an Add-On to Antipsychotics in Chronic and Treatment-Resistant Schizophrenia. Psychopharmacol. Bull. 2025, 55, 41–59. https://doi.org/10.64719/pb.4520.
- 44.
Brandalise, F.; Roda, E.; Ratto, D.; et al. Hericium erinaceus in Neurodegenerative Diseases: From Bench to Bedside and Beyond, How Far from the Shoreline? J. Fungi 2023, 9, 551. https://doi.org/10.3390/jof9050551.
- 45.
Nahar, L.; Charoensup, R.; Kalieva, K.; et al. Natural products in neurodegenerative diseases: Recent advances and future outlook. Front. Pharmacol. 2025, 16, 1529194. https://doi.org/10.3389/fphar.2025.1529194.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Suite 4002 Level 4, 447 Collins Street, Melbourne, Victoria 3000, Australia
General Inquiries: info@sciltp.com