Application of Medicinal Mushrooms for the Treatment of Peripheral Nerve Injury: A Systematic Review

<b>Background/Objective</b>: Current treatments for peripheral nerve injury (PNI) lack robust evidence to suggest complete recovery; hence, alternative therapeutics offer new opportunities to develop more effective protocols. Mushroom species and their related components are considered potential candidates for peripheral nerve repair, but their specific effects and underlying mechanisms are not fully understood. This systematic review presents the available evidence on the use of mushroom species for PNI therapy, including the bioactive components and mechanisms of action. <b>Methodology</b>: A comprehensive literature search in three databases (PubMed, Scopus, and Google Scholar) led to the synthesis of 11 records published between 2010 and 2024. Qualitative analysis revealed the neuroregenerative potential of four mushrooms: <i>Amanita muscaria</i> (<i>n</i> = 2), <i>Hericium erinaceus</i> (<i>n</i> = 5), <i>Lignosus rhinocerotis</i> (<i>n</i> = 3), and <i>Flammulina velutipes</i> (<i>n</i> = 1), with aqueous extracts as the most common type of ingredients used (<i>n</i> = 4) relative to specific components such as muscimol, polysaccharide, Erinacine S, and nerve-guided conduits (NGCs). <b>Results</b>: These mushroom-derived treatments enhanced the migration of Schwann cells mainly via the FGF-2 signalling and MAPK pathway. In vivo studies also revealed the ability of <i>H. erinaceus</i>, <i>A. muscaria</i>, and <i>L. rhinocerotis</i> to promote peripheral nerve repair and functional recovery, with evidence suggesting the role of neurotrophic factors, anti-apoptotic signalling, and pro-inflammatory substances. <i>H. erinaceus</i> was identified as the most promising for potential clinical applications, given the stronger evidence-based data and its relatively safer components compared to <i>A. muscuria</i> and other mushroom species. <b>Conclusions</b>: Despite presenting the potential use of mushrooms in managing PNIs, the existing approaches need to be subjected to clinical research to accelerate the development of future therapeutics and preventive measures for PNIs.