Neurogenesis-dependent antidepressant-like activity of Hericium erinaceus in an animal model of depression

Abstract

Background Depression is a severe neuropsychiatric disorder that affects more than 264 million people worldwide. The efficacy of conventional antidepressants are barely adequate and many have side effects. Hericium erinaceus (HE) is a medicinal mushroom that has been reported to have therapeutic potential for treating depression. Methods Animals subjected to chronic restraint stress were given 4 weeks HE treatment. Animals were then screened for anxiety and depressive-like behaviours. Gene and protein assays, as well as histological analysis were performed to probe the role of neurogenesis in mediating the therapeutic effect of HE. Temozolomide was administered to validate the neurogenesis-dependent mechanism of HE. Results The results showed that 4 weeks of HE treatment ameliorated depressive-like behaviours in mice subjected to 14 days of restraint stress. Further molecular assays demonstrated the 4-week HE treatment elevated the expression of several neurogenesis-related genes and proteins, including doublecortin, nestin, synaptophysin, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphorylated extracellular signal-regulated kinase, and phosphorylated cAMP response element-binding protein (pCREB). Increased bromodeoxyuridine-positive cells were also observed in the dentate gyrus of the hippocampus, indicating enhanced neurogenesis. Neurogenesis blocker temozolomide completely abolished the antidepressant-like effects of HE, confirming a neurogenesis-dependent mechanism. Moreover, HE induced anti-neuroinflammatory effects through reducing astrocyte activation in the hippocampus, which was also abolished with temozolomide administration. Conclusion HE exerts antidepressant effects by promoting neurogenesis and reducing neuroinflammation through enhancing the BDNF-TrkB-CREB signalling pathway.

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

“…The culinary-medicinal mushroom Hericium erinaceus, also known as the lion's mane mushroom, is well known for its diverse therapeutic activities related to neuroprotection [127,[157][158][159][160] and neuroregeneration [161][162][163] attributed to its antioxidant properties [127,160,164]. In a study by Lew et al [127], a standardized aqueous extract of H. erinaceus has been shown to possess higher total phenolic content and more potent reducing power compared to solvent extracts.…”

Mycotherapy: Potential of Fungal Bioactives for the Treatment of Mental Health Disorders and Morbidities of Chronic Pain

“…Currently, the biggest challenge associated with psychedelic pharmacology studies is prohibition where psychedelics are classed as a Schedule 1 drug and the social stigma associated with their use. Chong et al, 2021 implied a predictive analysis method to investigate the molecular mechanisms of H. erinaceus [ 124 ], perhaps this offers a novel means of determining efficacy prior to clinical trials in line with prohibition. Other methods including ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis to investigate fungal biologics may also be implemented.…”

“…Additionally, in vivo studies on depressed animals demonstrated that when fed with H. erinaceus levels of the monoamine’s serotonin, dopamine and NE were elevated [ 123 ]. In vivo studies report that erinacine can increase monamine expression and modulate anti-inflammatory brain-derived neurotrophic factor (BDNF) signalling in depressed animals [ 124 ]. Amycenone, a proprietary mixture of compounds which are present in the fruiting body of H. erinaceus , demonstrated anti-inflammatory activity against cytokines TNF and IL and reduced inflammatory induced depression in test animals [ 119 ] a similar activity observed with SSRIs and SNRIs.…”

“…To this end, many of the studies involving the psychedelics and compounds which alter consciousness have been carried out in the presence of psychiatrists and counselling professionals specifically trained in psychedelic psychotherapy. Some alternative methods of determining activity have been utilized based on gene ontology, predictive analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to investigate fungal biologics [ 124 ].…”

The Monkey Head Mushroom and Memory Enhancement in Alzheimer’s Disease

“…Hericium erinaceus (HE), also known as the monkey’s head mushroom, lion’s mane mushroom, or Yamabushitake, is commonly found in East Asia [ 18 ] ( Figure 1 ). It is well-known for its diverse therapeutic activities, including neuroprotection [ 16 , 17 , 19 , 20 ] and neuroregeneration [ 21 , 22 , 23 , 24 ], which are attributed to its neurogenesis, antioxidative, and anti-neuroinflammatory functions [ 17 , 19 , 20 , 23 , 25 ].…”