Neuroprotective Effects of Hericium erinaceus: Evidence from Experimental and Clinical Studies—A Systematic Review and Limited Meta-Analysis

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.