Hericium erinaceus Extract Reduces Anxiety and Depressive Behaviors by Promoting Hippocampal Neurogenesis in the Adult Mouse Brain

Abstract

Versatile biological activities of Hericium erinaceus (HE) have been reported in many brain diseases. However, roles of HE in major psychiatric disorders such as depression and anxiety remain to be investigated. Therefore, we evaluated whether HE could reduce anxiety and depressive behaviors in the adult mouse and its underlying mechanisms. Male C57BL/6 mice were administered HE (20 or 60 mg/kg, p.o.) or saline once a day for 4 weeks. Open field and tail suspension tests were performed 30 min after the last administration of HE, followed by forced swim test 2 days later. We found that chronic administration of HE showed anxiolytic and antidepressant-like effects. To elucidate possible mechanisms, proliferative activity of the hippocampal progenitor cells was assessed by immunohistochemistry of proliferating cell nuclear antigen (PCNA) and Ki67. Moreover, to evaluate neuronal survival in the dentate gyrus, 5-bromo-2'-deoxyuridine (BrdU) (120 mg/kg, i.p.) was given at the first day of HE administration, followed by isolation of the brains 4 weeks later. HE (60 mg/kg) increased the number of PCNA- and Ki67-positive cells in the subgranular zone of the hippocampus, indicating increased proliferation of hippocampal progenitors. In addition, BrdU- and BrdU/NeuN-positive cells in the dentate gyrus were significantly increased when treated with HE (60 mg/kg) compared with the saline-treated group, demonstrating enhanced neurogenesis by HE treatment. Taken together, the results indicate that chronic HE administration can exert anxiolytic and antidepressant-like effects, possibly by enhancing adult hippocampal neurogenesis.

Therapeutic Potential of Hericium erinaceus for Depressive Disorder

“…However, they did not detect an anxiolytic effect in the elevated plus-maze, which contradicted the previous findings by Ryu et al in 2018 [32]. One possible reason for this discrepancy is that the two studies used different H. erinaceus extracts, as Chiu et al (2018) used the ethanolic extract enriched with erinacine A extracted from the mycelium [31], whereas Ryu et al (2018) used the ethanolic extract from the fruiting body [32]. Further research on the anxiolytic effects of H. erinaceus is required to confirm these findings.…”

“…They showed that the extracts enriched with erinacine A reduced the immobility time in both the forced swim test and tail suspension test, indicating it had antidepressant-like effects. However, they did not detect an anxiolytic effect in the elevated plus-maze, which contradicted the previous findings by Ryu et al in 2018 [32]. One possible reason for this discrepancy is that the two studies used different H. erinaceus extracts, as Chiu et al (2018) used the ethanolic extract enriched with erinacine A extracted from the mycelium [31], whereas Ryu et al (2018) used the ethanolic extract from the fruiting body [32].…”

“…Increased levels of NGF were found to be associated with neurogenesis and neuroplasticity [48], which may potentially lead to antidepressant-like effects. A study by Ryu et al (2018) found that chronic administration of H. erinaceus ethanolic extract (60 mg/kg) significantly increased the number of PCNA-positive cells and Ki67-positive cells in the…”

“…The study by Ryu et al in 2018 investigated the antidepressant and anxiolytic effects of H. erinaceus ethanolic extract in adult mice [32]. They found that chronic administration of a high dose (60 mg/kg) H. erinaceus extract significantly reduced the time spent in the peripheral region of the open field test, suggesting a potential anxiolytic effect.…”

“…Moreover, H. erinaceus has been used to treat cognitive impairments [27], Alzheimer's disease [28], Parkinson's disease [29], ischemic stroke [30], and presbycusis [14]. Recently, the present research on H. erinaceus has been focused on its antidepressant-like effects for the treatment of depressive disorder [31][32][33]. Up to date, no review concerning the antidepressant effects of H. erinaceus is available.…”