Article

Effects of Hericium erinaceus on amyloid β(25-35) peptide-induced learning and memory deficits in mice

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The mushroom Hericium erinaceus has been used as a food and herbal medicine since ancient times in East Asia. It has been reported that H. erinaceus promotes nerve growth factor secretion in vitro and in vivo. Nerve growth factor is involved in maintaining and organizing cholinergic neurons in the central nervous system. These findings suggest that H. erinaceus may be appropriate for the prevention or treatment of dementia. In the present study, we examined the effects of H. erinaceus on amyloid β(25-35) peptide-induced learning and memory deficits in mice. Mice were administered 10 µg of amyloid β(25-35) peptide intracerebroventricularly on days 7 and 14, and fed a diet containing H. erinaceus over a 23-d experimental period. Memory and learning function was examined using behavioral pharmacological methods including the Y-maze test and the novel-object recognition test. The results revealed that H. erinaceus prevented impairments of spatial short-term and visual recognition memory induced by amyloid β(25-35) peptide. This finding indicates that H. erinaceus may be useful in the prevention of cognitive dysfunction.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Both erinacine-based compounds and hericenone induce the biosynthesis of NGF in neurons [16]. In a study on rats, the administration of erinacine A led to an adjustment of NGFs in two areas of the brain, locus coeruleus and hippocampus [20,[22][23][24][25][26]. These areas of the brain are usually affected in patients with dementia and AD. ...
... These areas of the brain are usually affected in patients with dementia and AD. The administration of erinacine A in mice with Alzheimer's and induced Parkinson's improved the symptoms of both diseases [24][25][26]. A group of diterpenoids isolated from cultured mycelia of H. erinaceus, namely, erinacines, was demonstrated to be a potential enhancer of NGF biosynthesis in cultured astrocytes and increased production of NGF is correlated with proper neural growth and maintenance [22]. ...
... A group of diterpenoids isolated from cultured mycelia of H. erinaceus, namely, erinacines, was demonstrated to be a potential enhancer of NGF biosynthesis in cultured astrocytes and increased production of NGF is correlated with proper neural growth and maintenance [22]. Notably, erinacine A has been reported to exhibit a protective effect against ischemic injury, Parkinson's, and AD in vivo [20,24,25]. Therefore, erinacine A-enriched H. erinaceus attracts attention and may serve as a promising agent with neurotrophic activity, potentially easing neurodegenerative disorders [16]. ...
Article
Full-text available
Hericium erinaceus (H. erinaceus) is a rare and appreciated fungal species belonging to the division Basidiomycota used for centuries in traditional Chinese medicine for its medicinal value. This species of mushrooms brings the most diverse benefits for the human body, and can have beneficial effects for treating Alzheimer's disease (AD). This study investigated whether ethanolic extract from the fungal biomass of H. erinaceus enhances cognitive function via the action on cholinergic neurons using the scopolamine (SCOP)-induced zebrafish (Danio rerio) model of memory impairment. The ethanolic extract from the fungal biomass of H. erinaceus was previously obtained using an ultrasonic extraction method (UE). The administration of H. erinaceus extract to zebrafish, with a pattern of AD induced by scopolamine, showed an improvement in memory evaluated by behavioral and biochemical tests on brain tissue. These results suggest that H. erinaceus has preventive and therapeutic potentials in managing memory deficits and brain oxidative stress in zebrafish with AD.
... 11,12 In particular, erinacine, one of the diterpeniods, is reported to facilitate nerve growth factor (NGF) expression and secretion. 13 Given that NGF plays pleiotropic roles in diverse brain diseases, including Alzheimer's disease, 14 HE could alleviate memory deficits in animal models 15,16 as well as in human patients with Alzheimer's disease. 17 Moreover, HE administration reduced stroke-induced cerebral infarction. ...
... 18,33 When narrowed down to active ingredients of HE in relation to NGF, the majority of studies focused on erinacines and hericenones, showing improved neurite out-growth. [11][12][13]15,20 Taken together, NGF, possibly stimulated by crude HE extracts that contain erinacines and hericenones, can boost adult hippocampal neurogenesis. However, as many new bioactive compounds comprising HE are actively being identified, 34,35 it will be interesting to find out whether novel molecules are present in the extract that mediates adult hippocampal neurogenesis after chronic HE administration. ...
Article
Full-text available
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.
... In in vitro assays, extracts from H. erinaceus were reported to stimulate NGF synthesis and/or promote NGF-induced neurite outgrowth in various cell types [14,15]. In in vivo assays, H. erinaceus's fruiting bodies exhibited significant anti-dementia activity [16,17]. The 2 of 13 aqueous extract from fruiting bodies also promoted the injured nerve regeneration in a Sprague-Dawley rat model [18]. ...
... The known compounds were identified by comparing their spectral data with those reported in the literature. [16,17]. The aqueous extract from fruiting bodies also promoted the injured nerve regeneration in a Sprague-Dawley rat model [18]. ...
Article
Full-text available
Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6) and one new natural product (2) together with five known compounds (1,3–5,7) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1) and a cyathane diterpenoid, erincine A (3), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells.
... Do kategorie léèivých hub patøí také u nás málo známý korálovec ježatý (Hericum eri- naceus); Jiang et al., 2014, oznaèovaný v Èínì jako Hou Tou Gu a v Japonsku yamabushitake (Lindequist et al., 2010). Tato jedlá houba, která má své pevné místo v tradièní èínské medicínì v terapii nemocí trávicího systému (Wong et al., 2013), má mimo jiné také antidepresivní (Nagano et al., 2010) a neuroprotektivní úèinky (Lee et al., 2014) a chrání mozek pøed neurodegenerativními pochody, vèetnì Alzheimerovy a Parkinsonovy choroby (Mori et al., 2011; Phan et al., 2014). ...
... Pokud jim však byly po dobu tøí týdnù podávány houby H. erinaceus, jejich orientace v bludišti se výraznì zlepšila. Navíc se tyto myši staly zvídavìjšími – vìnovaly více èasu zkoumání nových pøedmìtù ve srovnání s tìmi, které už znaly (Mori et al., 2011). Stamets poukazuje na japonskou klinickou studii Moriho et al. (2009), která prokázala významné pozitivní úèinky této houby u lidí s mírnou kognitivní poruchou. ...
Article
Full-text available
SOUHRN Houby jsou považovány za funkèní potraviny a zdroj fyziologicky prospìšných látek. Nedávné výzkumy ukázaly, že jedlé houby mohou hrát dùležitou roli v prevenci mnoha neurologických poruch spojených se stáøím, vèetnì Alzheimerovy a Parkinsonovy choroby. Herici-um erinaceus je jedlá houba, která má dlouhou historii použití v tradièní èínské medicínì. Tato houba je bohatá na nìkteré fyziologicky významné složky, zejména beta-glukanové polysacharidy, které jsou odpovìdné za protirakovinné, imunomodulaèní, hypolipidemické, antioxidaèní a neuroprotektivní úèinky houby. Tento pøehledový èlánek shrnuje nedávné pokroky ve výzkumu H. erinaceus, diskutuje o možné prospìšnosti této houby a poukazuje na bioaktivní látky zodpovìdné za její léèivé vlastnosti. SUMMARY Mushrooms are considered as nutritionally functional foods and source of physiologically beneficial medicines. Recent evidence demonstrates that edible mushrooms may play an important role in the prevention of many age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Hericium erinaceus is an edible fungus, which has a long history of usage in traditional Chinese medicine. This mushroom is rich in some physiologically important components, especially beta-glucan polysaccharides, which are responsible for anti-cancer, immuno-modulating, hypolipidemic, antioxidant and neuro-protective activities of this mushroom. This review article has summarized recent advances in the research and study on H. erinaceus and discussed the potential health beneficial effects of this mushroom with the recognition of bioactive compounds responsible for these medicinal properties.
... However, in most of the animal and human experiments, Hericium erinaceus fruiting body and its extracts were used as the study object. They were not only supported by many cell experiments, but the protective effect in mice ischemic brain injury was also shown in animal models [16] to ameliorate learning and memory impairment in mice [17], rat sport repair neural damage [18], and human mild cognitive impairment [19]. An intervention of three 350 mg/g H. erinaceus mycelia enriched with 5 mg/g erinacine A capsules for 49 weeks achieved a better contrast sensitivity in mild Alzheimer's disease patients, when compared to a placebo group, and may be important in achieving neurocognitive benefits [20]. ...
... In the early study of Kawagishi et al. [2], hericenones isolated from fruiting body of Hericium erinaceus extract could promote neural cell growth. In recent years, Hazekawa et al. [16] and Mori et al. [17] also confirmed the neural protective and memory-improving effect of Hericium erinaceus in mice. Wong et al. [14] found that polysaccharide extract of Hericium erinaceus fruiting body could promote peripheral nerve regeneration after a nerve injury crush in rats. ...
Article
Full-text available
Hericium erinaceus is a well-known edible and medicinal mushroom. Its fruiting bodies and mycelia exhibit various bioactive components including polysaccharides, terpenoids, erinacines, and hericenones. It also have various pharmacological activities, such as immunomodulation, antitumor, antioxidant, antimicrobe, neuroprotection and enhancing memory functions. The objective of this study was to investigate protection and repair functions of brain cells in zebrafish embryos by treatment of hot water and ethanol extracts from Hericium erinaceus solid-state fermented soybean and adlay mix products. The results showed that the crude polysaccharide and crude triterpenoids contents in water and ethanol extracts from Hericium erinaceus solid-state fermented soybeans and adlay mix product were 65.18% and 10.85%, respectively. They were 6.87 and 3.97 folds fruiting body extracts. Zebrafish embryos pre-soaking 24 h in different concentrations (50, 100 and 200 ppm) of water and ethanol extracts of Hericium erinaceus solid-state fermented product significantly reduced the number of died brain cells impaired by 1 % ethanol soaking 24 h in a dose-dependent, 200 ppm extract had the best protection effect as the control. Moreover, both 200 ppm water and ethanol extracts from Hericium erinaceus solid-state fermented product had significantly better repair effects in brain cells of zebrafish embryo impaired by 1% ethanol pre-soaking 4 h; they also had better effects than extracts from Hericium erinaceus fruiting body.
... 16 In mice, oral administration of H. erinaceus prevents amyloid β (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) peptide-induced impairment of spatial short-term memory and visual recognition memory. 17 Orally delivered H. erinaceus was found to confer neuroprotection in mice in which the middle cerebral artery was occluded. 18 Furthermore, scores on a cognitive function scale improved following oral administration of H. erinaceus to patients with mild cognitive impairment. ...
... A failure was defined as repeated entry into the same arm (ABA, ACA, AAB, AAC, BAB, BCB, BBC, BBC, CBC, CAC, CCB, or CCA). 17 The number of arm entries and the number of triads were measured. The percentage alternation was computed by dividing the number of triads by the number of possible alternations (number of entries − 2) and then multiplying by 100. ...
Article
Hericium erinaceus is an edible and medicinal mushroom with potential neuroprotective effects. The study of H. erinaceus has attracted considerable attention during the past 10 years, particularly with regard to its potential utility in the treatment of motor dysfunction, Alzheimer disease, and other forms of dementia. We previously determined that oral supplementation with H. erinaceus results in significant improvements in novelty-seeking behavior and novel object recognition in mice. In this study, H. erinaceus was added to the diets of wild-type mice for 2 months, and effects on spatial memory were evaluated by means of a Y maze and an object location task. We found that H. erinaceus increased general locomotor activity but had no effect on spatial memory. Thus, oral supplementation with H. erinaceus yields specific and selective improvements in recognition memory without altering spatial working memory, which supports the hypothesis that recognition memory can be modeled as a dual process. In this model, the perirhinal cortex supports the recognition of individual items as part of a circuit involved in familiarity with an encountered stimulus, whereas the hippocampus supports recollected associations and relationships between stimuli.
... Interestingly, hericenones and erinacines have been shown to effectively cross the BBB (Hu et al. 2019) and proven to have neuroprotective effect both in vitro and in vivo in animal models of peripheral nerve injury (Wong et al. 2012), stroke (Hazekawa et al. 2010) and Alzheimer's disease (Friedman 2015;Mori et al. 2011;Kawagishi & Zhuang 2008). This suggested a dual action on the peripheral and central nervous system. ...
... in Alzheimer's disease mouse models (Tsai-Teng et al. 2016;Mori et al. 2011) suggesting a yet to be defined activity on the CNS. A recent study has determined that erinacine A and hericenones C and D were capable of slowing cognitive declines in a model of frailty (Ratto et al. 2019). ...
Preprint
Full-text available
The traditional medicinal mushroom Hericium erinaceus has long been known for enhancing the peripheral nerve regeneration through targeting nerve growth factor (NGF) neurotrophic activity. It was also reported to protect against ageing-dependent cognitive decline in wildtype and in Alzheimer's disease mouse models suggesting a yet to be defined action on neurons of the central nervous system. Here, we purified and identified biologically active compounds from H. erinaceus, based on their ability to promote neurite outgrowth in hippocampal neurons. N-de phenylethyl isohericerin (NDPIH), an isoindoline compound from this mushroom together with its hydrophobic derivative hericene A, were highly potent in inducing extensive axon outgrowth and neurite branching in the absence of serum demonstrating high neurotropic activity. NDPIH also induced enlarged growth cones suggestive of a brain-derived neurotrophic factor (BDNF)-like activity. Pharmacological inhibition of tropomyosin receptor kinase B (TrkB) by ANA12 prevented NDPIH-induced neurotrophic activity providing evidence that NDPIH acts via TrkB receptors to mediate its neurotrophic effect in central neurons. Finally, in vivo treatment with H. erinaceus crude extract and hericene A significantly increased BDNF and downstream pathway and enhanced learning and memory in the novel object recognition memory test. Our results suggest that hericene A can promote BDNF-like activity in neurons in vitro and in vivo thereby enhancing recognition memory.
... Encouragingly, H. erinaceus displays neuroprotective properties, such as facilitating nerve growth factor (NGF) expression and secretion and regulating the differentiation and development of cholinergic neurons in in vitro and in vivo experiments [2]. Recently, H. erinaceus has been reported to improve visual cognitive memory and mediate spatial short-term memory damage in an Aβ-induced mouse model analyzed via behavioral tests [17]. Taken together, these studies suggest that H. erinaceus may have beneficial effects on neurodegenerative diseases. ...
Article
Full-text available
Hericium erinaceus, an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson’s and Alzheimer’s disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl3 combined with d-galactose-induced Alzheimer’s disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation. A 3 h HE incubation at doses of 50 and 100 µg/mL before 25 mM of l-Glu effectively reversed the reduction of cell viability and the enhancement of the nuclear apoptosis rate in DPC12 cells. Compared with l-Glu-damaged cells, in PC12 cells, HE suppressed intracellular reactive oxygen species accumulation, blocked Ca²⁺ overload and prevented mitochondrial membrane potential (MMP) depolarization. In the Alzheimer’s disease mouse model, HE administration enhanced the horizontal and vertical movements in the autonomic activity test, improved the endurance time in the rotarod test, and decreased the escape latency time in the water maze test. It also improved the central cholinergic system function in the Alzheimer’s mice, demonstrated by the fact that it dose-dependently enhanced the acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations in both the serum and the hypothalamus. Our findings provide experimental evidence that HE may provide neuroprotective candidates for treating or preventing neurodegenerative diseases.
... Специальные лабораторные исследования этого гриба показали, что H. erinaceum способен предотвратить нарушения пространственной краткосрочной памяти и визуального распознавания, благодаря наличию амилоидных β (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) пептидов. Это открытие указывает на то, что этот гриб может быть полезен в профилактике когнитивной дисфункции [37]. ...
Article
Full-text available
Medicinal mushrooms have become an attractive topic due to their bioactive compounds potentially useful for therapeutic use. Among the growing popularity of medicinal mushrooms is Hericium erinaceus. Hericium erinaceus is a medicinal edible mushroom with a long history of use in traditional Chinese medicine as well as in other countries of the East. Along with this, several of its biologically active compounds served as the basis for the creation of nutritional supplements. Its fruiting bodies and mycelium are rich in active substances that promote health. Tests of substances extracted from this fungus in animals and in vitro have given good results. They are beginning to be used in the treatment of cancer, liver diseases, Alzheimer’s and Parkinson’s diseases, and wound healing. They improve cognitive abilities, support the nervous and immune systems.
... Results revealed that the consumption of cookies enriched with 0.5 g of powdered fruiting bodies relieves depression, anxiety, frustration, and palpitation. Mori et al. 47 examined the effects of dietary supplementation with freeze-dried fruiting bodies on intracerebroventricular injection of Aβ 25-35 -induced learning and memory deficits in mice. The diet prevented impairments of spatial short-term memory and visual recognition memory. ...
Article
Culinary and medicinal mushrooms have been appreciated since prehistoric times as valuable resources for food and medicine. Edible mushrooms represent an untapped source of nutraceuticals and valuable palatable food. Long considered tonics, they are now treasured as functional foods that can improve human health and quality of life. Numerous studies have provided insights into the neuroprotective effects of edible mushrooms, which are attributed to their antioxidant, antineuroinflammatory, and cholinesterase inhibitory properties, and their ability to prevent neuronal death. Here we review the recent literature on the role of culinary and medicinal mushrooms in the management of neurodegenerative diseases and neurotrauma. We highlight some of the molecular mechanisms for how these alternative medicines provide health benefits that could help us to harness their neuroprotective effects.
... This mushroom can improve sleep quality, ameliorate depression and alleviate the mild cognitive impairment [45,46]. Mori et al. [47] examined the effect of oral administration of H. erinaceus powder added to the mouse diet over a 23 day experimental period on the amyloid b(25-35) peptide-induced learning and memory deficits (cognitive dysfunctions) in mice. The results revealed that H. erinaceus prevented the cognitive deficits induced by amyloid b (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) peptide, so that, this mushroom may be a promising treatment for the prevention of cognitive dysfunction. ...
Article
Mushroom species have the potential to be developed into functional foods for their high nutritional value and because they are a source of biologically active compounds of medicinal importance. The investigation on the beneficial properties of edible mushrooms has gained attention by the scientific community during the last decades. In the light of the emerging literature, the objective of this review was to compile the more recent information about the health benefits associated to the edible mushrooms intake. It can be concluded that the consumption of mushrooms as a part of daily diet could be a natural adjuvant for the treatment and prevention of several chronic diseases.
... In mice, dietary supplementation with H. erinaceus prevents the impairment of spatial short-term and visual recognition memory induced by amyloid (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) peptide [2]. Recently, Hazekawa et al. [3] described the neuroprotective effects of H. erinaceus dietary supplementation in mice subjected to middle cerebral artery occlusion. ...
Article
Full-text available
Hericium erinaceus (Bull.) Pers. is a medicinal mushroom capable of inducing a large number of modulatory effects on human physiology ranging from the strengthening of the immune system to the improvement of cognitive functions. In mice, dietary supplementation with H. erinaceus prevents the impairment of spatial short-term and visual recognition memory in an Alzheimer model. Intriguingly other neurobiological effects have recently been reported like the effect on neurite outgrowth and differentiation in PC12 cells. Until now no investigations have been conducted to assess the impact of this dietary supplementation on brain function in healthy subjects. Therefore, we have faced the problem by considering the effect on cognitive skills and on hippocampal neurotransmission in wild-type mice. In wild-type mice the oral supplementation with H. erinaceus induces, in behaviour test, a significant improvement in the recognition memory and, in hippocampal slices, an increase in spontaneous and evoked excitatory synaptic current in mossy fiber-CA3 synapse. In conclusion, we have produced a series of findings in support of the concept that H. erinaceus induces a boost effect onto neuronal functions also in nonpathological conditions.
... In addition, we demonstrate that H. erinaceus treatment resulted in a significant increase of LXA4 in most of the brain regions examined and modulated expression of cytoprotective proteins, such as HO-1, Hsp70 and Trx. Our results are consistent with recent evidence obtained in mice, showing neuroprotection by H. erinaceus on Ab25-35 peptide-induced cognitive dysfunction [38,39]. In this study the powder of H. erinaceus was mixed with a normal powdered diet and the Ab25-35 peptide was administered by intracerebroventricular injection. ...
Article
Full-text available
Background: There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. Results: Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding. Conclusions: Conceivably, activation of LXA4 signaling and modulation of stress responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage.
... Hericenones isolated from the fruiting body and erinacines isolated from the mycelium of HE promoted nerve growth factor (NGF) biosynthesis in rodent astrocytes cultures (15). HE also prevented cognitive deficits induced by intracerebroventricular administration of amyloid β (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) peptide in mice (18). HE has been found to be effective in improving mild cognitive impairment in humans, which might be attributable to NGF synthesis promoting effect by hericenones (16). ...
Article
Full-text available
Hericium erinaceus (HE), an edible mushroom, has been used as a herbal medicine in several Asian countries since ancient times. HE has potential as a medicine for the treatment and prevention of dementia, a disorder closely linked with circadian rhythm. This study investigated the effects of the intake of HE extracts on behavioral rhythm, photosensitivity of the circadian clock, and clock gene mRNA expression in the suprachiasmatic nucleus (SCN), a central clock, in mice. Although the HE ethanol extract only affected the offset time of activity, the HE water extract advanced the sleep–wake cycle without affecting the free-running period, photosensitivity, or the clock gene mRNA expression in SCN. In addition, both extracts decreased wakefulness around end of active phase. The findings of the present study suggest that HE may serve as a functional food in the prevention and treatment of Alzheimer’s disease and delayed sleep phase syndrome.
... Moreover, compounds isolated from its fruiting bodies and mycelia exhibit a potent activity to stimulate NGF expression and secretion in vitro and in vivo [10,11]. Recent studies demonstrated anti-dementia activity of its fruiting bodies in mice with cognitive deficits induced by Aβ and in people with mild cognition impairment [12,13]. However, the anti-dementia activity of Hericium erinaceus mycelia remained unclear. ...
Article
Full-text available
Background The fruiting body of Hericium erinaceus has been demonstrated to possess anti-dementia activity in mouse model of Alzheimer’s disease and people with mild cognitive impairment. However, the therapeutic potential of Hericium erinaceus mycelia on Alzheimer’s disease remains unclear. In this study, the effects of erinacine A-enriched Hericium erinaceus mycelia (HE-My) on the pathological changes in APPswe/PS1dE9 transgenic mouse model of Alzheimer’s disease are studied. Results After a 30 day oral administration to 5 month-old female APPswe/PS1dE9 transgenic mice, we found that HE-My and its ethanol extracts (HE-Et) attenuated cerebral Aβ plaque burden. It’s worth noting that the attenuated portion of a plaque is the non-compact structure. The level of insulin-degrading enzyme was elevated by both HE-My and HE-Et in cerebral cortex. On the other hand, the number of plaque-activated microglia and astrocytes in cerebral cortex and hippocampus were diminished, the ratio of nerve growth factor (NGF) to NGF precursor (proNGF) was increased and hippocampal neurogenesis was promoted after these administrations. All the mentioned benefits of these administrations may therefore improve the declined activity of daily living skill in APPswe/PS1dE9 transgenic mice. Conclusions These results highlight the therapeutic potential of HE-My and HE-Et on Alzheimer’s disease. Therefore, the effective components of HE-My and HE-Et are worth to be developed to become a therapeutic drug for Alzheimer’s disease.
... It was previously reported that HE extracts have neuroprotective effects, promote normal development of cultivated cerebellar cells and have regulatory effects on the development of myelin genesis processes in vitro [10]. The ethanol extract of HE has been shown to induce nerve growth factor expression and to prevent Aβ 25-35 -induced impairment of memory functions in animal experiments [11,12]. Oxidative stress has been shown to be involved in the initiation and progression of various disorders caused by oxygen radicals, which damages lipids, proteins and nucleic acids [13,14]. ...
Article
Full-text available
Background Hericium erinaceus (HE) is a well-known mushroom in traditional Chinese food and medicine. HE extracts from the fruiting body and mycelia not only exhibit immunomodulatory, antimutagenic and antitumor activity but also have neuroprotective properties. Here, we purified HE polysaccharides (HEPS), composed of two high molecular weight polysaccharides (1.7 × 105 Da and 1.1 × 105 Da), and evaluated their protective effects on amyloid beta (Aβ)-induced neurotoxicity in rat pheochromocytoma PC12 cells. Methods HEPS were prepared and purified using a 95 % ethanol extraction method. The components of HEPS were analyzed and the molecular weights of the polysaccharides were determined using high-pressure liquid chromatography (HPLC). The neuroprotective effects of the polysaccharides were evaluated through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and an MTT assay and by quantifying reactive oxygen species (ROS) and mitochondrial membrane potentials (MMP) of Aβ-induced neurotoxicity in cells. Result Our results showed that 250 μg/ml HEPS was harmless and promoted cell viability with 1.2 μM Aβ treatment. We observed that the free radical scavenging rate exceeded 90 % when the concentration of HEPS was higher than 1 mg/mL in cells. The HEPS decreased the production of ROS from 80 to 58 % in a dose-dependent manner. Cell pretreatment with 250 μg/mL HEPS significantly reduced Aβ-induced high MMPs from 74 to 51 % and 94 to 62 % at 24 and 48 h, respectively. Finally, 250 μg/mL of HEPS prevented Aβ-induced cell shrinkage and nuclear degradation of PC12 cells. Conclusion Our results demonstrate that HEPS exhibit antioxidant and neuroprotective effects on Aβ-induced neurotoxicity in neurons.
... It is used as a food and herbal medicine in Japan and China without harmful effects [1]. The mushroom may be a good candidate for inducing neuronal differentiation and promoting neuronal survival [2]. Both the mycelium (erinacines A-I) and the fruiting bodies (Hericenone C-H) are the source of many bioactive extracts with drug efficacy. ...
Article
Full-text available
Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.
... Administration of lion's mane mushroom extracts enhances learning abilities and improves memory [118]. Extracts of lion's mane mushroom are appropriate in the prevention of dementia thanks to the enhancement of cognitive functions [119]. ...
Article
Full-text available
Hericium erinaceum (Bull.: Fr.) Pers. is an edible fungus of great significance in medicine. It is rarely found in Europe, in contrast, it is common in Japan and North America. Its fruitbodies have been well-known for hundreds of years in traditional Chinese medicine and cuisine. A cradle of H. erinaceum cultivation is Asia. In Eastern Europe is rare in natural habitats, but can be successfully cultivated. Both fruitbodies and mycelia are rich in active, health promoting substances. Tests of substances extracted from this mushroom carried out on animals and in vitro have given good results. They can be used in the treatment of cancer, hepatic disorders, Alzheimer’s and Parkinson’s diseases, wound healing. They improve cognitive abilities, support the nervous and immune systems. Promising results have been reported in clinical trials and case reports about the human treatment (e.g., recovery from schizophrenia, an improvement of the quality of sleep, alleviation of the menopause symptoms). The subject of this paper is to summarize information about the development of mycelium, the best conditions for cultivation of fruitbodies, bioactive substances and their use in medicine.
... The stereochemistry of erinacine R (46) was elucidated by Ma et al. 2008 (Fig. 9). Several studies were conducted on the mechanisms involved in the neuroprotection process of the brain from extracts from H. erinaceus (Hazekawa et al. 2010;Mori et al. 2008Mori et al. , 2009Mori et al. , 2011Phan et al. 2014). Lee et al. (2014) found the effects of erinacine A, which is capable of preventing ischemic injury to neurons; possibly act as an antiinflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. ...
Article
Full-text available
DOI 10.1007/s11557-015-1105-4. Online Medicinal mushrooms have become a compelling topic because the bioactive compounds they contain promise a plethora of therapeutic properties. Hericium erinaceus commonly known as “Houtou” or “Shishigashira” in China and “Yamabushitake” in Japan, has commonly been prescribed in Traditional Chinese Medicine (TCM), because its consumption has been shown to be beneficial to human health. The species is found throughout the northern hemisphere in Europe, Asia, and North America. Hericium erinaceus has been firmly established as an important medicinal mushroom and its numerous bioactive compounds have been developed into food supplements and alternative medicines. However, the correspondence of the active components that cause the observed effects is often not clear. The mushroom as well as the fermented mycelia have been reported to produce several classes of bioactive molecules, including polysaccharides, proteins, lectins, phenols, and terpenoids. Most interestingly, two classes of terpenoid compounds, hericenones and erinacines, from fruiting bodies and cultured mycelia, respectively, have been found to stimulate nerve growth factor (NGF) synthesis. In this review we examine the scientific literature to explore and highlight the scientific facts concerning medicinal properties of H. erinaceus. We provide up-to-date information on this mushroom, including its taxonomy and a summary of bioactive compounds that appear related to the therapeutic potential of H. erinaceus. See http://link.springer.com/article/10.1007/s11557-015-1105-4
... The effects of Hericium erinaceus on Ab25-35 peptideinduced cognitive dysfunction in mice was investigated by Mori et al. (2011). The powder of H. erinaceus was mixed with a normal powdered diet and the Ab25-35 peptide was administered by intracerebroventricular injection. ...
... 21 Sterols, such as Fermentative mycelia Glucose ergosterol confer antioxidative properties. 21,22 Hericium erinaceus has been found to be the most potent in vitro inhibitor of both low-density lipoprotein (LDL) oxidation and HMG Co-A reductase activity, suggesting therapeutic potential for the prevention of oxidative stress-mediated vascular diseases. 23 ...
Article
Full-text available
Hericium erinaceus, most commonly known as lion’s mane, is an edible fungus, with a long history of use in Traditional Chinese Medicine. The mushroom is abundant in bioactive compounds including β-glucan polysaccharides; hericenones and erinacine terpenoids; isoindolinones; sterols; and myconutrients, which potentially have neuroprotective and neuroregenerative properties. Because of its anti-inflammatory properties and promotion of nerve growth factor gene expression and neurite (axon or dendrite) outgrowth, H. erinaceus mycelium shows great promise for the treatment of Alzheimer’s and Parkinson’s diseases. The fungus was well tolerated in two clinical studies, with few adverse events reported.
... An increase in NGF mRNA has been detected in the hippocampus, but not cortex, of mice given 5% of the diet as lion's mane for a period of seven days to around 1.3-fold of control (Mori et al., 2008). Hericium appears to protect rats against cognitive decline caused by β-amyloid pigmentation at 5% of the diet (Mori et al., 2011). ...
... Erinacines isolated from its mycelia have been known to possess a potent stimulating effect on nerve growth factor (NGF) expression and secretion [13]. Recent studies have demonstrated that H. erinaceus fruiting body ameliorated Aβ-induced cognitive declined in mice and people with mild cognitive impairment [14,15]. Our previous studies also demonstrated that H. erinaceus mycelium ameliorated Aβ-induced cognitive decline in mice [16]. ...
Article
Full-text available
Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid β production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid β and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid β production and is worth to be further developed for AD therapeutic use.
... However, our study shows for the first time that HE pretreatment modulates vitagenes expression in PC12 cells. Our results are consistent with evidence obtained in mice, showing neuroprotection by HE on Aβ25-35 peptide-induced cognitive dysfunction [49]. ...
Article
Full-text available
Hericium Erinaceus (HE) is a medicinal plant known to possess anticarcinogenic, antibiotic, and antioxidant activities. It has been shown to have a protective effect against ischemia-injury-induced neuronal cell death in rats. As an extending study, here we examined in pheochromocytoma 12 (PC12) cells, whether HE could exert a protective effect against oxidative stress and apoptosis induced by di(2-ethylhexyl)phthalate (DEHP), a plasticizer known to cause neurotoxicity. We demonstrated that pretreatment with HE significantly attenuated DEHP induced cell death. This protective effect may be attributed to its ability to reduce intracellular reactive oxygen species levels, preserving the activity of respiratory complexes and stabilizing the mitochondrial membrane potential. Additionally, HE pretreatment significantly modulated Nrf2 and Nrf2-dependent vitagenes expression, preventing the increase of pro-apoptotic and the decrease of anti-apoptotic markers. Collectively, our data provide evidence of new preventive nutritional strategy using HE against DEHP-induced apoptosis in PC12 cells.
... In animal models, its active compounds have demonstrated the ability to delay neuronal death in neurodegenerative diseases such as ischemic stroke, Parkinson's disease, AD, and depression, and it has been shown to promote nerve regeneration and functional recovery in neuropathic pain or presbycusis [199]. In addition, lion's mane has been shown to prevent the loss of spatial short-term and visual recognition memory induced by Aβ25-35 in mice [200]. Similarly, it has been shown in vitro that lion's mane fruiting body extract induces neurite outgrowth of neuron cells NG108-15 and PCI2 cells, promotes nerve growth factor (NGF) mRNA expression, and modulates the secretion of NGF from 1321N1 human astrocyte cells [201]. ...
Article
Full-text available
Background and aim: Brain health is becoming more important to the average person as the number of people with cognitive impairments, such as Alzheimer's disease (AD), is rising significantly. The current Food and Drug Administration-approved pharmacotherapeutics for dementia neither cure nor halt cognitive decline; they just delay the worsening cognitive impairment. This narrative review summarizes the effects of nutrients and phytonutrients on cognitive function. Methods: A comprehensive literature search of PubMed was performed to find clinical trials in humans that assessed the effects of nutrients and phytonutrients on cognitive function published in English between 2000 and 2021. Six independent reviewers evaluated the articles for inclusion in this review. Results: Ninety-six articles were summarized in this narrative review. In total 21 categories of nutrients and phytonutrients were included, i.e., α-lipoic acid, Bacopa monnieri, B vitamins, cholinergic precursors, vitamin D, vitamin E, Ginkgo biloba, ginseng, lion's mane mushroom, N-acetyl cysteine, omega-3 fatty acids, aloe polysaccharides, Rhodiola rosea, rosemary, saffron, tart cherries, turmeric, wild yam, Withania somnifera, xanthines, and zinc. Particular noteworthy effects on cognition included memory, recollection, attention, intelligence, vocabulary, recognition, response inhibition, arousal, performance enhancement, planning, creative thinking, reaction time, vigilance, task switching, orientation to time, place, and person, reading, writing, comprehension, accuracy, learning, information processing speed, executive function, mental flexibility, daily functioning, decrease in mental fatigue, and freedom from distractibility. Some nutrients and phytonutrients also improved mood and contentedness and reduced anxiety and the need for caregiving. These effects are not completely consistent or ubiquitous across all patient populations or health statuses. Adverse effects were minimal or nonexistent. Conclusion: Due to the growing population of people with cognitive impairment and the lack of effective pharmacotherapeutics, it is prudent for those afflicted or their caregivers to find alternative treatments. Our narrative review shows that many of these nutrients and phytonutrients may be promising for treating some aspects of cognitive impairment, especially for people afflicted with AD. Relevance for patients: As demonstrated in a number of clinical trials, healthy adults and patients with various health challenges (e.g., AD, mild cognitive impairment, multiple sclerosis, and Parkinson's disease) exhibiting a wide range of severity in cognitive defects would be best served to consider multiple nutrients and phytonutrients to improve aspects of their cognitive function.
... Both in-vitro and in vivo studies showed no adverse effect of H. erinaceus. According to Mori et al.[66], a diet containing H. erinaceus powder prevented ...
Chapter
Mushrooms are used not only for culinary purposes, but also for the treatment of various chronic diseases. It shows vital therapeutic activity in several neurodegenerative disorders such as, Alzheimer's and Parkinson's diseases. These diseases are non-communicable as well as age-related. Currently, no drug therapy is available to treat such neurodegenerative disorders; instead, it is best to delay progression of these diseases. Accumulated evidence has suggested that culinary or medicinal mushrooms may play a significant role in the prevention of these disorders, as mentioned earlier, and dementia. Therefore, daily consumption of mushrooms in the diet may improve memory and cognitive functions, including mushrooms such as, Hericium Erinaceus, Ganoderma lucidium, Pleurotus giganteus, Dictyophora indusiata, Sarcodon scabrosus, Antrodia camphorata Termitomyces albuminosus, Paxillus panuoides, Mycoleptodonoides aitchisonii, Lignosus rhinocerotis, and numerous other species. These mushrooms show potent antioxidative, antiinflammatory, and memory-enhancing activities. This chapter deals with the therapeutic activity of mushrooms and their bioactive components for different neurodegenerative diseases. Thus, mushrooms can be considered supportive and promising candidates for treating or preventing neurodegenerative diseases.
... Ma et al. 2010;Nagano et al. 2010;Mori et al. 2011;Kim et al. 2014;Phan et al. 2014a Phan et al. , b, 2019Thongbai et al. 2015;Cheng et al. 2016;Kuo et al. 2016;Zhang et al. 2016a;Spelman et al. 2017;Chong et al. 2019;Jang et al. 2019;Kushairi et al. 2019;Saitsu et al. 2019;Üstün and Ayhan 2019;Limanaqi et al. 2020;Yadav et al. 2020). ...
Book
Diversity of wild and cultivated macrofungi as edible and medicinal mushrooms has long been known by humans as a source of valuable food and medicines used by tradipraticians. In the fungal kingdom, macrofungi taxonomically belong to two phyla, the Basidiomycota (class Agaricomycetes) and Ascomycota (class Pezizomycetes). Macrofungi have been used in traditional Asian and European Medicines, and based on 90,000 known worldwide distributed mushroom species, are considered an important resource for modern clinical and pharmacological research. They are regarded as a source of high- and low-molecular-weight bioactive compounds (alkaloids, lipids, phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) with more than 130 therapeutic effects (anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, etc.). There is also scientific evidence of using macrofungi as neuroprotectants, that is, Agaricus blazei (= Agaricus subrufescens), Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Pleurotus ostreatus, and Trametes versicolor. However, their neuroprotective effects have not been fully explored. This review discusses recent advances in research on the neuroprotective potential of macrofungi and perspectives for their application as neuroprotectants in biomedicine to prevent, support, or cure neurodegenerative disorders.
... Ma et al. 2010;Nagano et al. 2010;Mori et al. 2011;Kim et al. 2014;Phan et al. 2014a Phan et al. , b, 2019Thongbai et al. 2015;Cheng et al. 2016;Kuo et al. 2016;Zhang et al. 2016a;Spelman et al. 2017;Chong et al. 2019;Jang et al. 2019;Kushairi et al. 2019;Saitsu et al. 2019;Üstün and Ayhan 2019;Limanaqi et al. 2020;Yadav et al. 2020). ...
Chapter
Full-text available
Badalyan S.M. et Rapior S. The neurotrophic and neuroprotective potential of macrofungi. In: Medicinal Herbs and Fungi – Neurotoxicity vs. Neuroprotection. Agrawal D.C. et Dhanasekaran M. (Eds). Publisher Springer. Chapter 2: 37-78 (2021). doi:10.1007/978-981-33-4141-8_2 ____ Diversity of wild and cultivated macrofungi as edible and medicinal mushrooms has long been known by humans as a source of valuable food and medicines used by tradipraticians. In the fungal kingdom, macrofungi taxonomically belong to two phyla, the Basidiomycota (class Agaricomycetes) and Ascomycota (class Pezizomycetes). Macrofungi have been used in traditional Asian and European Medicines, and based on 90,000 known worldwide distributed mushroom species, are considered an important resource for modern clinical and pharmacological research. They are regarded as a source of high- and low-molecular-weight bioactive compounds (alkaloids, lipids, phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) with more than 130 therapeutic effects (anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, cytotoxic, hepatoprotective, hypocholesterolemic, hypoglycemic, hypotensive, immunomodulatory, etc.). There is also scientific evidence of using macrofungi as neuroprotectants, that is, Agaricus blazei (= Agaricus subrufescens), Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Pleurotus ostreatus, and Trametes versicolor. However, their neuroprotective effects have not been fully explored. This review discusses recent advances in research on the neuroprotective potential of macrofungi and perspectives for their application as neuroprotectants in biomedicine to prevent, support, or cure neurodegenerative disorders. Corresponding authors: s.badalyan@ysu.am, sylvie.rapior@umontpellier.fr
... Previously, another edible-medicinal mushroom, Hereicium erinaceus, had been reported to enhance NOR performance of the Aβ 25-35 infused AD mice. 19 G. lucidum HWE might have facilitated learning related neuronal plasticity and long-term potentiation that aided in better object recognition and memory reconsolidation. 20 In the current study only male rats were used. ...
Article
Full-text available
Alzheimer's disease (AD) is the leading neurodegenerative disorder affecting memory and learning of aged people. Hypercholesterolemia had been implicated as one of the stark hallmarks of AD. Recent AD control guidelines have suggested lifestyle modification to slow down the progression of AD. In this regard, medicinal mushroom Ganoderma lucidum seems apt. In the present study, hot water extract of G. lucidum (200 mg/kg body weight) was fed to the hypercholesterolemic and AD model rats for 8 weeks. Nonspatial memory and learning abilities of the model animals was assessed using novel object recognition (NOR) test, rotarod test, and locomotor/open-field test. Then, the animals were sacrificed and transmission electron micrograph (TEM) view of the hippocampal neurons was assessed. In all the nonspatial memory and learning tests, the G. lucidum HWE fed rats performed better indicating improved memory and learning abilities. TEM view showed regular arrangement of the neurons in the G. lucidum HWE fed rats compared with those of the deranged arrangement of the AD rats. G. lucidum might have aided in restoring the memory and learning abilities of the AD model animals through maintaining neuronal structure and function. Thus, G. lucidum could be suggested as a medicotherapeutic agent against AD. KEY WORDS: Ganoderma lucidum, Alzheimer's disease, amyloid beta, nonspatial memory and learning, novel object recognition test, open-field test, rotarod test, medicinal mushrooms ABBREVIATIONS: A, Alzheimer's disease model rat; Aβ, amyloid β; AD, Alzheimer's disease; AE, G. lucidum hot water extract fed Alzheimer's disease model rats; C, control rats; CE, G. lucidum hot water extract fed control rats; H, hypercholesterolemic rats; HE, G. lucidum hot water extract fed hypercholesterolemic rats; HWE, hot water extract; NOR, novel object recognition; OF, open field
... • H. erinaceus extract is shown to attenuate the effects of Amyloid Beta in mice. The study reported that mice on a H. erinaceus based diet that were were prevented from peptide induced spatial short-term and visual recognition memory impairment [8] . ...
Poster
Poster presented to summarize the neuroprotective and bioactive properties of a selection of ethnomedically important macrofungi in South East Asia.
... 1−3 By consuming the mushroom fruiting bodies or extracts, numerous positive physiological effects have been reported on the nervous, digestive, circulatory, and immune systems. 4 In particular, nervous system effects 5,6 such as the stimulation of the nerve growth factor (NGF) gene expression and enhancement of the neurite outgrowth 7 are considered to be beneficial for the prevention and treatment of dementia, 8,9 a cognitive disorder occurring in super-aged societies in developed countries. Some of the clinical testing data show that the continual oral intake of tablets containing dry samples of H. erinaceus led to improved cognitive functions. ...
Article
The first total syntheses of hericenones C–H and “putative 3-hydroxyhericenone F” were achieved. Highlights of the synthesis include the straightforward construction of the resorcinol core and geranyl side chain, assembly of the natural product skeleton by sequential O-geranylation and a clay/zeolite-mediated O → C rearrangement reaction, and a biomimetic cyclization to form a variety of bicyclic natural hericenones and their congeners. The structure of the “putative 3-hydroxyhericenone F” was revised as the 5-exo cyclization product (named: hericenone Z) of epoxyhericenone C through in-depth analyses of the cyclization modes in addition to NMR spectroscopic studies. To gain insights into the biological functions of geranyl-resorcinols in Hericium erinaceus, potential neuroprotective effects against endoplasmic reticulum (ER) stress-dependent cell death were evaluated systematically to clarify a fundamental structure–activity relationship. Among the compounds assayed, the linoleate-containing hericenone analogue, i.e., the regioisomer of hericene D, was found to possess the most potent neuroprotective effect against tunicamycin and thapsigargin-induced ER stress-dependent cell death.
... Thus, by stimulating NE and NGF/BDNF synthesis, H. erinaceus may produce plastic effects which are expected to counteract behavioural alterations besides neurotoxicity. In fact, H. erinaceus reverses early learning and memory deficits which are induced by amyloid beta peptides independently of neuropathology in AD mice models [114]. ...
Article
Full-text available
Recent studies focused on the pharmacology and feasibility of herbal compounds as a potential strategy to target a variety of human diseases ranging from metabolic to brain disorders. Accordingly, bioactive ingredients which are found within a variety of herbal compounds are reported to produce both neuroprotective and psychotropic activities which may help to combat mental disorders such as depression, anxiety, sleep disturbances and cognitive alterations. In the present manuscript, we focus on three herbs which appear effective in mitigating anxiety or depression with favourable risk-benefit profiles, namely Scutellaria baicalensis (S. baicalensis), Hericium erinaceus (H. erinaceus) and Rhodiola rosea (R. rosea). These three traditional folk medicinal herbs target the main biochemical events that are implicated in mental disorders, mimicking, to some extent, the mechanisms of action of conventional antidepressants and mood stabilizers with a wide margin of tolerability. In detail, they rescue alterations in neurotransmitter and neuro-endocrine systems, stimulate neurogenesis and the synthesis of neurotrophic factors, and they counteract oxidative stress, mitochondrial dysfunction and inflammation. Albeit the encouraging results that emerge from both experimental and clinical evidence, further studies are needed to confirm and better understand the mental-health promoting, and specifically, the antidepressant effects of these herbs.
... Recent studies also show that fungal protein from H. erinaceus exhibited immunomodulatory activities which can be an adjunct drug for immunotherapy [10]. Several reports also demonstrated its stimulating activity to the synthesis of nerve growth factor which might have a preventive and ameliorative effect in age-related neurological dysfunctions such as Alzheimer's disease and Parkinson's disease [11,12,13]. It is also reported that the polysaccharide in the fruiting body may have a positive influence on immune function which can be beneficial against stomach, esophageal, and skin cancer [14]. ...
Article
Full-text available
Hericium mushrooms are edible fungi belonging to the Hericiaceae family with a long history of usage in traditional medicine in China. In the Philippines, however, information on its production, cultivation or nutraceutical properties is relatively unknown. In this study, four strains of Hericium spp. including H. americanum, H. erinaceus, H. coralloides and Hericium sp. were evaluated for their nutritional requirements using various commercially available culture media and their antibacterial activity against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 in two dilutions (60 ml and 80 ml sterile distilled water + 12-hour culture - bacterial suspension) on Mueller Hinton Agar. Highest mycelial growth response of H. americanum and H. coralloides was observed on Sabouraud Dextrose Agar while H. erinaceus and Hericium sp. grew best on Potato Dextrose Agar. The ability of H. americanum mycelia to inhibit bacterial growth at 12 and 24 hours after inoculation against E. coli was reported. Meanwhile, both H. americanum and H. erinaceus demonstrated antibacterial activity against S. aureus ATCC 25923 in both dilutions.
... In Chinese folk medicine, H. erinaceus is used to treat tumors of the digestive system such as esophageal cancer, gastric cancer and duodenal cancer [13,14]. According to various studies, extracts from the fruiting body and mycelium of H. erinaceus provide many health benefits, such as anti-oxidizing properties [15,16], anti-inflammatory properties [17,18], the promotion of neuron growth and regeneration [19][20][21], the prevention of memory loss [22,23], and the activation of other physiological functions. For example, recent studies have shown that 4-chloro-3,5-dimethoxybenzoic methyl ester and erincine A isolated from H. erinaceus enhance NGF-induced neurite outgrowth and protect neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells [21]. ...
Article
Full-text available
Previous studies have revealed the anti-inflammatory and neuroprotective properties of Hericium erinaceus extracts, including the fact that the active ingredient erinacine C (EC) can induce the synthesis of nerve growth factor. However, there is limited research on the use and mechanisms of action of EC in treating neuroinflammation. Hence, in this study, the inflammatory responses of human BV2 microglial cells induced by LPS were used to establish a model to assess the anti-neuroinflammatory efficacy of EC and to clarify its possible mechanisms of action. The results showed that EC was able to reduce the levels of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) proteins produced by LPS-induced BV2 cells, in addition to inhibiting the expression of NF-κB and phosphorylation of IκBα (p-IκBα) proteins. Moreover, EC was found to inhibit the Kelch-like ECH-associated protein 1 (Keap1) protein, and to enhance the nuclear transcription factor erythroid 2-related factor (Nrf2) and the expression of the heme oxygenase-1 (HO-1) protein. Taken together, these data suggest that the mechanism of action of EC involves the inhibition of IκB, p-IκBα, and iNOS expressions and the activation of the Nrf2/HO-1 pathway.
... Hericium erinaceus, also known as Yamabushitake or Lion's Mane, is an exceptional health-promoting species. H. erinaceus has a neuroprotective role in neurodegenerative diseases, in vitro and in preclinical studies [40][41][42]. The H. erinaceus fruiting body and mycelia contain an exceptionally large amount of structurally different bioactive components, including polysaccharides, erinacines, hericerins, steroids, alkaloids, and lactones that play roles preventing, alleviating, or treating major diseases, including cancer, depression, diabetes, lipidaemia, and neurodegenerative diseases [43,44]. ...
Article
Full-text available
Epidemiological data indicate that subjects affected by obesity have an increased risk of developing mood disorders. The relationship between obesity and mood disorders is bidirectional. We assessed whether a Hericium erinaceus treatment improved depression, anxiety, sleep, and binge eating disorders after 8 weeks of supplementation in subjects affected by overweight or obesity under a low calorie diet regimen. Looking for a possible clinical biomarker, we assessed the serum balance between brain-derived neurotrophic factor (BDNF) and its precursor pro-BDNF before and after H. erinaceus supplementation. Seventy-seven volunteers affected by overweight or obesity were recruited at the offices of the Department of Preventive Medicine, Luigi Devoto Clinic of Work, Obesity Centre, at the IRCCS Foundation Policlinico Hospital of Milan (Italy). Patients were recruited only if they had a mood and/or sleep disorder and/or were binge eating as evaluated through self-assessment questionnaires. We used two different enzyme-linked immunosorbent assays kits to discriminate circulating levels of pro-BDNF and BDNF. Eight weeks of oral H. erinaceus supplementation decreased depression, anxiety, and sleep disorders. H. erinaceus supplementation improved mood disorders of a depressive-anxious nature and the quality of the nocturnal rest. H. erinaceus increased circulating pro-BDNF levels without any significant change in BDNF circulating levels.
Article
Hericium erinaceus is an important mushroom with edible values and medicinal properties. Both the mycelium and the fruiting bodies contain many bioactive compounds with drug efficacy. Recent evidence demonstrates that it is helpful to various diseases, such as Alzheimer's disease, immunoregulatory, and many types of cancer. Furthermore, emerging pieces of evidence have shown that different active molecules in H. erinaceus have different functions on different organs in different diseases via the different mechanisms. Drawing on current research results, this review mainly focuses on the therapeutic effects of H. erinaceus on various diseases of multiple physiological systems, including the nervous system, digestive system, circulatory system, and immune system. This paper also discusses systematically the efficient protection of H. erinaceus against the diseases from the intricate experimental proofs by using the systematic viewpoints, which provides a framework for future research directions.
Article
Abstract On the search for anti-inflammatory compounds from natural Korean medicinal sources, a bioassay-guided fractionation and chemical investigation of the MeOH extract from the fruiting bodies of Hericium erinaceum resulted in the isolation and identification of five benzyl alcohol derivatives (1-5). In this study, their anti-inflammatory effects on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators were examined using RAW 264.7 macrophage cells. The structures of isolates were identified by comparing their spectroscopic data with previously reported values. The analysis of their inhibitory activities on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophage cells showed that erinacerin B (2) and hericenone E (4) decreased the levels of NO and PGE2 production in a concentration-dependent manner. Next, this study was performed to examine their mechanism of action on the regulation of NO and PGE2 production. Compounds 2 and 4 were found to block the LPS-induced phosphorylation of two major inflammatory transcription factors, NF-κB (p65/p50) and AP-1 (c-Jun and c-Fos). Taken together, these results suggest that down-regulation of LPS-induced NO and PGE2 production by compounds 2 and 4 is mediated through the modulation of NF-κB and AP-1 activation in macrophage cells. These results impact the development of potential health products for preventing and treating inflammatory diseases.
Article
Full-text available
Hericium erinaceus (commonly known as lion’s mane mushroom) is an edible mushroom used in traditional Chinese medicine. It is a prolific producer of diverse bioactive metabolites with neuroprotective and neuroregenerative properties (e.g. β-glucan polysaccharides, hericenones, erinacine terpenoids, isoindolinones, sterols, and myconutrients). Because of its anti-inflammatory properties and promotion of nerve growth factor (NGF) gene expression and neurite (axon or dendrite) outgrowth, H. erinaceus is used for the treatment of Alzheimer's as well as Parkinson's diseases. This review provides a comprehensive account of the bioactive compounds from H. erinaceus (both from the fruit bodies and mycelia) and their biological activities such as neuroprotective functions, cytotoxicity, anticarcinogenic, antidiabetic, antimicrobial, and herbicidal activities. Keywords – Alzheimer’s disease – anticancer agents – antidiabetic – anti-inflammatory – antimicrobial – erinacine terpenoids – herbicidal – hericenone – neurite outgrowth – neuroprotection – Parkinson’s disease
Article
Helicium erinaceus (HE) is a fungal mushroom habiting in the mountainous areas of northeast territories. HE has been used in the traditional folk medicines and medicinal cuisine in China, Korea and Japan. It has been implicated in a variety of physiological functions such as anti-aging, anti-cancer, anti-gastritis, anti-metabolic diseases, etc. Hence, HE is an attractive target resource for developing not only medicines but also functional foods. Basic studies on the physiological functions and the chemical identification of its active ingredients have progressed in recent decades. In this article, we provide an overview of the biochemical and pharmacological studies of HE, especially of its antitumor and neural preserving functions, together with recent developments in the chemical analysis of its polysaccharides which comprise its major active components.
Article
The culinary and medicinal mushroom Hericium erinaceus is widely consumed in Asian countries, but apparently not in the United States, for its nutritional and health benefits. To stimulate broader interest in the reported beneficial properties, this overview surveys and consolidates the widely scattered literature on the chemistry (isolation and structural characterization) of polysaccharides and secondary metabolites such as erinacines, hericerins, hericenones, resorcinols, steroids, mono- and diterpenes, and volatile aroma compounds, nutritional composition, food and industrial uses, and exceptional nutritional and health-promoting aspects of H. erinaceus. The reported health-promoting properties of the mushroom fruit bodies, mycelia, and bioactive pure compounds include antibiotic, anticarcinogenic, antidiabetic, antifatigue, antihypertensive, antihyperlipodemic, antisenescence, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties and improvement of anxiety, cognitive function, and depression. The described anti-inflammatory, antioxidative, and immunostimulating properties in cells, animals, and humans seem to be responsible for the multiple health-promoting properties. A wide range of research advances and techniques are described and evaluated. The collated information and suggestion for further research might facilitate and guide further studies to optimize the use of the whole mushrooms and about 70 characterized actual and potential bioactive secondary metabolites to help prevent or treat human chronic, cognitive, and neurological diseases.
Article
Chronic low-grade inflammation in the adipose tissue accompanying obesity is thought to be an underlying driver of metabolic diseases. In this study, we aimed to investigate the efficacy of Hericium erinaceus on adipose tissue inflammation. The anti-inflammatory effects of the ethyl acetate soluble fraction of H. erinaceus (EAHE) were examined using cocultures of 3T3-L1 adipocytes and RAW264 macrophages. EAHE significantly suppressed tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in cultured RAW264 macrophages stimulated by lipopolysaccharide (LPS). EAHE also caused notable inhibition of c-Jun N-terminal kinase (JNK) activation, which is thought to be involved in the suppression of proinflammatory cytokines by EAHE. In a coculture system with 3T3-L1 and RAW264 cells stimulated with LPS, EAHE reduced TNF-α and IL-6 concentrations in the conditioned medium and lowered the gene expression levels of these cytokines in 3T3-L1 adipocytes. Furthermore, EAHE suppressed the LPS-induced reduction of adiponectin mRNA levels in 3T3-L1 adipocytes cocultured with RAW264 macrophages. However, in 3T3-L1 adipocytes cultured alone, the concentration of LPS used in this study did not affect the gene expression levels of these adipokines. We attributed the anti-inflammatory effects of EAHE on 3T3-L1 adipocytes cocultured with RAW264 macrophages to the suppression of Toll-like receptor 4 (TLR4) signaling and subsequent proinflammatory cytokine secretion in RAW264 cells. Our findings indicate the possibility that H. erinaceus exerts anti-inflammatory effects on macrophages through the inhibition of TLR4-JNK signaling and prevents or ameliorates adipose tissue inflammation associated with obesity.
Article
In traditional medicine, a variety of plants have shown favorable effects in the therapy of diseases associated with cognitive dysfunction and memory loss. Lately, a large number of phytoconstituents have been studied for their potential in the treatment of Alzheimer's disease, including compounds that inhibit acetylcholinesterase, demonstrate antioxidant activity, have anti-inflammatory effects, inhibit beta-amyloid accumulation or tau aggregation, and improve mitochondrial dysfunction. This article discusses the current situation of basic research and clinical trials on substances derived from medicinal plants to provide basic data for further research and new drug development. Copyright © 2015 Prous Science, S.A.U. or its licensors. All rights reserved.
Article
We studied the effect of ethyl acetate (EA) fraction from Acer okamotoanum on cognitive improvement and protective abilities in amyloid beta (Aβ)25–35 peptide-injected Alzheimer’s disease (AD) mice. EA was oral administration at 100 and 200 mg/kg/day during the 14 days. We studied the protective effect of EA against AD on the basis of behavioral tests including T-maze test, Novel object recognition test, and Morris water maze test. Control group injected with Aβ25–35 showed significant impairments in memory function. But the oral administration of EA (EA 100 and EA 200 groups) improved the cognition and memory function. In addition, EA against Aβ25–35 peptide has been shown to inhibit lipid peroxidation levels and nitric oxide production in tissues. Acetylcholinesterase (AChE) was elevated in the brain by Aβ25–35 peptide, whereas administration of EA (EA 100 and EA 200 groups) significantly decreased AChE level. Our results indicated that EA improves learning and long-term memory against Aβ25–35 peptide–caused deficit through attenuation of oxidative stress.
Book
Researchers have tried various effective treatments that prevent the progressive neurodegeneration of neurons within the brain. Parkinson’s disease (PD), Alzheimer’s disease (AD), and Multiple sclerosis (MS) are some of the most common neurodegenerative diseases (NDDs).Recent Advances in the Treatment of Neurodegenerative Disorders provides interesting updates on treatments of these neurological disorders. Ten chapters have been contributed by experts in pharmacology and give a unique perspective to reader on special topics in this area, including the treatment of neurodegenerative treatment of neurodegenerative disease through ayurveda and phytochemicals, the therapeutic role of vitamins in Parkinson’s disease, mushrooms in NDD treatment, MS treatment, ALS treatment and the use of nanoparticles and nano formulations in NDD treatment. This is an informative reference for pharmacologists, medicinal chemists and healthcare professionals (general practitioners and neurologists) seeking updates in the treatment of some common neurodegenerative disorders.
Chapter
Mushrooms, the macro-fungi with distinctive fruiting bodies and mycelia, are valued throughout the world not only for their nutritive values but also for their medicinal uses. The former desirable property of mushrooms derives out of their rich contents of vitamins, trace elements, and minerals and appetite-enhancing flavors, but the therapeutic values result from its antioxidant and immunomodulatory activities, from its ability to activate very specific neuronal receptors, and from its capacity to rejuvenate cellular metabolism. Reactive oxygen species cause extensive damage to cells and tissues by interfering with normal metabolism, which are aggravated during stressful environments, such as during infections, stress, metabolic diseases, and various degenerative disorders including neurodegenerative diseases, cardiovascular diseases, and accelerated or normal aging. Mushrooms contain many biologically dynamic compounds, some of which are neuroactive substances, free radical scavengers, anti-apoptotic factors, and nerve growth factor stimulators that exert positive effects on brain cells, all of which essentially qualify them as good neuro-nutraceuticals that help in the protection of different neural cells, in vivo and in vitro. While discussing the neuroprotective and neuromodulatory properties of mushrooms, we rationally postulate here indirect benefits of these fungi through the enhanced environment for gut microbiome that are meaningful for healthy brain functions.
Article
Full-text available
The Himalayan forests of Uttarakhand represent a natural repository for the rich biodiversity of the Indian subcontinent. Forest resources in this region form an integral part of socio-economy and cultural practices. Mushrooms are forest products which have been used as food for a long time but very few for therapeutic purposes, which is associated to the lack of awareness and knowledge. If properly identified, these mystic organisms can be very promising in prevention and cure of various ailments. The present study is a part of macrofungal exploration carried out from 2015–2016. As a result, 15 mushroom species are identified which possess a spectrum of bioactive compounds and therapeutic potential. All of these species are morphologically described along with the habit, habitat and notes on their healing capacities.
Chapter
Mushrooms have been used globally for various nutritional and medicinal values and now are gaining worldwide recognition due to its various health benefits and potent and unique pharmaceutical properties. Researchers in different parts of the world have demonstrated different species of mushrooms possessing immunomodulatory, antitumor, anticancer, antibacterial, antiviral, anti-inflammatory, anti-atherosclerotic, neuroprotective, antioxidant, and antihypoglycemic properties. The chapter presents an overview of the research on the therapeutic efficacy of mushrooms.
Article
Full-text available
Abstract Mushrooms have long been used not only as food but also for the treatment of various ailments. Although at its infancy, accumulated evidence suggested that culinary-medicinal mushrooms may play an important role in the prevention of many age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Therefore, efforts have been devoted to a search for more mushroom species that may improve memory and cognition functions. Such mushrooms include Hericium erinaceus, Ganoderma lucidum, Sarcodon spp., Antrodia camphorata, Pleurotus giganteus, Lignosus rhinocerotis, Grifola frondosa, and many more. Here, we review over 20 different brain-improving culinary-medicinal mushrooms and at least 80 different bioactive secondary metabolites isolated from them. The mushrooms (either extracts from basidiocarps/mycelia or isolated compounds) reduced beta amyloid-induced neurotoxicity and had anti-acetylcholinesterase, neurite outgrowth stimulation, nerve growth factor (NGF) synthesis, neuroprotective, antioxidant, and anti-(neuro)inflammatory effects. The in vitro and in vivo studies on the molecular mechanisms responsible for the bioactive effects of mushrooms are also discussed. Mushrooms can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro evidence and clinical trials with humans are needed.
Article
Full-text available
The neurodegeneration of Alzheimer's disease has been theorized to be mediated, at least in part, by insoluble aggregates of β-amyloid protein that are widely distributed in the form of plaques throughout brain regions affected by the disease. Previous studies by our laboratory and others have demonstrated that the neurotoxicity of β-amyloid in vitro is dependent upon its spontaneous adoption of an aggregated structure. In this study, we report extensive structure-activity analyses of a series of peptides derived from both the proposed active fragment of β-amyloid, β25–35, and the full-length protein, β1–42. We examine the effects of amino acid residue deletions and substitutions on the ability of β-amyloid peptides to both form sedimentable aggregates and induce toxicity in cultured hippocampal neurons. We observe that significant levels of peptide aggregation are always associated with significant β-amyloid-induced neurotoxicity. Further, both N- and C-terminal regions of β25–35 appear to contribute to these processes. In particular, significant disruption of peptide aggregation and toxicity result from alterations in the β33–35 region. In β1–42 peptides, aggregation disruption is evidenced by changes in both electrophoresis profiles and fibril morphology visualized at the light and electron microscope levels. Using circular dichroism analysis in a subset of peptides, we observed classic features of β-sheet secondary structure in aggregating, toxic β-amyloid peptides but not in nonaggregating, nontoxic β-amyloid peptides. Together, these data further define the primary and secondary structures of β-amyloid that are involved in its in vitro assembly into neurotoxic peptide aggregates and may underlie both its pathological deposition and subsequent degenerative effects in Alzheimer's disease.
Article
Full-text available
In aged rodents, impairments in learning and memory have been associated with an age-dependent decline in forebrain of cholinergic function, and recent evidence indicates that the cholinergic neurons in the nucleus basalis magnocellularis, the septal-diagonal band area and the striatum undergo age-dependent atrophy. Thus, as in Alzheimer-type dementia in man, degenerative changes in the forebrain cholinergic system may contribute to age-related cognitive impairments in rodents. The cause of these degenerative changes is not known. Recent studies have shown that the central cholinergic neurons in the septal-diagonal band area, nucleus basalis and striatum are sensitive to the neurotrophic protein nerve growth factor (NGF). In particular, intraventricular injections or infusions of NGF in young adult rats have been shown to prevent retrograde neuronal cell death and promote behavioural recovery after damage to the septo-hippocampal connections. It is so far not known, however, whether the atrophic cholinergic neurons in aged animals are responsive to NGF treatment. We report here that continuous intracerebral infusion of NGF over a period of four weeks can partly reverse the cholinergic cell body atrophy and improve retention of a spatial memory task in behaviourally impaired aged rats.
Article
Full-text available
Three experiments assessed the effects of beta-amyloid 1-40 (beta A4) on spatial learning in Sprague-Dawley rats. In Experiment 1, rats were trained on a signaled footshock avoidance in a Y-maze. Rats received a single injection of beta A4 or vehicle in both sides of the hippocampus immediately after the fifth trial. The beta A4 group took significantly longer than the vehicle group to learn to avoid the shock when trained to criterion 1 week later, suggesting a detrimental effect of beta A4 on memory consolidation. Experiment 2 used a food reinforcer rather than shock relief under procedures similar to Experiment 1. Again, the beta A4 group took longer to learn the maze to criterion. This shocks that the effect in Experiment 1 was not specific to shock-maintained learning. In Experiment 3, rats were trained to retrieve a food pellet from each arm of an eight-arm radial maze. After training to criterion, beta A4 or vehicle was administered intrahippocampally 30 min before the daily session for 26 sessions. There were no acute or chronic effects of beta A4 injection on radial maze performance, and no aggregation of beta A4 or significant necrosis was observed upon postmortem histological analysis. These experiments suggest that single injections of beta A4 impair memory consolidation, but repeated injections of beta A4 over an extended period do not affect well-learned behavior.
Article
Full-text available
A subtle but chronic alteration in metabolic balance between amyloid-β peptide (Aβ) anabolic and catabolic activities is thought to cause Aβ accumulation, leading to a decade-long pathological cascade of Alzheimer disease. However, it is still unclear whether a reduction of the catabolic activity of Aβ in the brain causes neuronal dysfunction in vivo. In the present study, to clarify a possible connection between a reduction in neprilysin activity and impairment of synaptic and cognitive functions, we cross-bred amyloid precursor protein (APP) transgenic mice (APP23) with neprilysin-deficient mice and biochemically and immunoelectron-microscopically analyzed Aβ accumulation in the brain. We also examined hippocampal synaptic plasticity using an in vivo recording technique and cognitive function using a battery of learning and memory behavior tests, including Y-maze, novel-object recognition, Morris water maze, and contextual fear conditioning tests at the age of 13–16 weeks. We present direct experimental evidence that reduced activity of neprilysin, the major Aβ-degrading enzyme, in the brain elevates oligomeric forms of Aβ at the synapses and leads to impaired hippocampal synaptic plasticity and cognitive function before the appearance of amyloid plaque load. Thus, reduced neprilysin activity appears to be a causative event that is at least partly responsible for the memory-associated symptoms of Alzheimer disease. This supports the idea that a strategy to reduce Aβ oligomers in the brain by up-regulating neprilysin activity would contribute to alleviation of these symptoms.
Article
Novel cytotoxic phenols, hericenone A () and B () were isolated from the mushroom . These structures were determined by interpretation of spectral data and chemical analyses.
Article
The structures of novel diterpenoids, erinacines A, B, and C, isolated from the cultured mycelia of Hericium erinaceum were determined by interpretation of the spectral data, and chemical and enzymatic reactions. These compounds showed potent stimulating activity of nerve growth factor (NGF)-synthesis.
Article
Novel compounds, hericenones C (3), D (4) and (5) were isolated from the mushroom Hericium erinaceum. These structures were determined by interpretation of the spectral data, and chemical and enzymatic reactions. These compounds have stimulating activity of the synthesis of nerve growth factor (NGF).
Article
Novel chromans, hericenones F, G and H were isolated from the mushroom Hericium erinaceum. These compounds stimulated the synthesis of nerve growth factor (NGF) in vitro.
Article
The structures of erinacines E, F and G from mycelia of Hericium erinaceum were determined by spectroscopic and/or X-ray analysis. Erinacines E and F exhibited potent stimulating activity against NGF synthesis by astroglial cells.
Article
The structures of erinacines E, F and G from mycelia of Hericium erinaceum were determined by spectroscopic and/or X-ray analysis. Erinacines E and F exhibited potent stimulating activity against NGF synthesis by astroglial cells.
Article
A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.
Article
Neurotrophic factors are essential to maintain and organize neurons functionally; thereby neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases such as Alzheimer's disease. In the present study, we firstly examined the effects of ethanol extracts of four edible mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and Agaricus blazei (Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among the four mushroom extracts, only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner. In addition, secretion of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned medium of 1321N1 cells incubated with H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones C, D and E, constituents of H. erinaceus, failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene expression by H. erinaceus extracts was inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus extracts induced phosphorylation of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting that H. erinaceus promotes NGF gene expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in vivo. ddY mice given feed containing 5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression in the hippocampus. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the JNK pathway; these compounds are not hericenones.
Article
Cholinergic neurons from the septum area, the vertical limb of the diagonal band of Broca, and the nucleus basalis of Meynert of postnatal 13-day-old rats were cultured with or without nerve growth factor (NGF) conditions. Total choline acetyltransferase (ChAT) activities, acetylcholine (ACh) contents, and survival numbers of cholinergic neurons in culture from each of three distinct regions were increased by NGF treatment, but little difference was found in cellular ChAT activities and ACh contents obtained in cultures with or without NGF. The result shows that NGF promotes the survival of cholinergic neurons from 13-day-old rats. Furthermore, the release of ACh from cultured neurons was investigated. The cells cultured with NGF showed a larger increase of the high K+-evoked ACh release than those cultured without NGF. However, NGF had no effect on spontaneous release. This suggests that NGF could regenerate and sustain the stimulation-evoked release mechanisms of ACh in cultured cholinergic neurons from postnatal rats.
Article
Cholinergic neuronal degeneration after axotomy has been proposed to be due to the loss of a retrogradely transported neurotrophic factor, possibly nerve growth factor (NGF). To test this hypothesis, NGF was continuously infused into the lateral ventricles of adult rats that had received bilateral lesions of all cholinergic axons projecting from the medial septum to the dorsal hippocampus. After 2 weeks of NGF treatment, identification of cholinergic neurons by the presence of the biosynthetic enzyme choline acetyltransferase revealed a dramatic increase (350%) in the survival of the axotomized septal cholinergic neurons. Thus, NGF or an NGF-like molecule can act as a neurotrophic factor for these neurons.
Article
The nucleus basalis of male Charles River Wistar rats was injected with 10 micrograms of the beta-amyloid peptides beta-(1-40) and beta-(25-35) and changes in the morphology of the lesioned area, the release of acetylcholine from the cortex, and in behavior were investigated. Injections of saline and a scrambled (25-35) peptide were used as controls. One week after lesioning, a Congo Red-positive deposit of aggregated material was found at the beta-peptides injection site, which lasted for about 21 days in the case of the beta-(25-35) peptide and at least two months for beta-(1-40). No deposit was detected after scrambled peptide injection. At one week post injection, an extensive glial reaction surrounded the injection site of all peptides and saline as well. Such a reaction was still present but rather attenuated after two months. A decrease in the number of cholinergic neurons was detected in the nucleus basalis after one week with all treatments except saline. After two months, a reduction in the number of choline acetyltransferase-immunopositive neurons was still detectable in the rats injected with beta-(1-40) but not in the beta-(25-35)-or scrambled-injected. The reduction in choline acetyltransferase immunoreactivity was closely paralleled by a decrease in basal acetylcholine release from the parietal cortex ipsilateral to the lesion. Disruption of object recognition was observed in the first weeks after beta-(25-35) peptide injection, whereas the beta-(1-40) peptide impaired the performance only two months after lesion. Rats with lesions induced by beta-peptides may be a useful animal model of amyloid deposition for investigation of the pathogenetic mechanisms leading to Alzheimer's disease.
Article
The neurodegeneration of Alzheimer's disease has been theorized to be mediated, at least in part, by insoluble aggregates of beta-amyloid protein that are widely distributed in the form of plaques throughout brain regions affected by the disease. Previous studies by our laboratory and others have demonstrated that the neurotoxicity of beta-amyloid in vitro is dependent upon its spontaneous adoption of an aggregated structure. In this study, we report extensive structure-activity analyses of a series of peptides derived from both the proposed active fragment of beta-amyloid, beta 25-35, and the full-length protein, beta 1-42. We examine the effects of amino acid residue deletions and substitutions on the ability of beta-amyloid peptides to both form sedimentable aggregates and induce toxicity in cultured hippocampal neurons. We observe that significant levels of peptide aggregation are always associated with significant beta-amyloid-induced neurotoxicity. Further, both N- and C-terminal regions of beta 25-35 appear to contribute to these processes. In particular, significant disruption of peptide aggregation and toxicity result from alterations in the beta 33-35 region. In beta 1-42 peptides, aggregation disruption is evidenced by changes in both electrophoresis profiles and fibril morphology visualized at the light and electron microscope levels. Using circular dichroism analysis in a subset of peptides, we observed classic features of beta-sheet secondary structure in aggregating, toxic beta-amyloid peptides but not in nonaggregating, nontoxic beta-amyloid peptides. Together, these data further define the primary and secondary structures of beta-amyloid that are involved in its in vitro assembly into neurotoxic peptide aggregates and may underlie both its pathological deposition and subsequent degenerative effects in Alzheimer's disease.
Article
Although a consensus on the primary mechanism(s) of neuronal degeneration in AD has not yet been reached, several potential pathogenic mechanisms have emerged. The involvement of APP and Aβ in the neurodegenerative process and their relationship to the tau-related neurofibrillary pathology are central issues. The pathogenic mechanism associated with inheritance of the ApoE4 allele remains to be determined, although initial investigations implicate effects on Aβ or possibly tau. Increasing evidence implicates oxidative stress in the neurodegenerative process, although this has yet to be convincingly linked to specific molecular mechanisms. Most importantly, the recent identification of new AD susceptibility genes promises to rapidly advance our understanding of the primary neurodegenerative mechanisms. In the broader context of human neurobiology, AD poses fundamental questions about how the brain ages and why the systems subserving memory and cognition are selectively vulnerable. The potential to answer these questions and treat this devastating illness makes this an exciting time in AD research.
Article
We explored amnesia induced by posttraining injection of beta-amyloid protein (beta A4) in four experiments. Previous reports showed that beta A4 impaired retention of learning maintained either by food reward or by shock relief. The experiments in this paper attempted to determine (1) if the amnesia is specific to the 1-40 beta A4 amino-acid sequence; and (2) if the amnesia can be attributed to a consolidation process. Subjects were 190 male Sprague-Dawley rats, 3 to 6 months old. Subjects were given five training trials on a left-right discrimination in a Y-maze with a food reward and injected immediately afterward with beta A4(1-40) or vehicle. One week later they were trained to criterion. Experiment 1 used a control group that was injected with the reverse-sequence peptide (40-1). The performance of the beta A4(40-1) group was unimpaired. Experiments 2 and 3 attempted to reverse the amnestic effects of beta A4 using noncontingent presentation of aspects of the training context during the retention interval. Experimental subjects in Experiment 2 were exposed to the Y-maze in the absence of reinforcers, 24, 22, and 2 h before retention testing. In Experiment 3, subjects were given a 1-min exposure to the reinforcers, outside the Y-maze, 24 h before retention testing. Both manipulations reversed beta A4-induced amnesia. In Experiment 4, beta A4-induced impairments were reversed by reinjecting beta A4 immediately before retention testing. Results indicate that beta A4 injected after partial training does not interfere with a consolidation process.
Article
Different putative toxic amyloid beta (A beta) peptides, beta (1-42), beta (1-40) and beta (25-35), were infused (0.75, 1.5 or 3 nmol) in the rat medial septum. Memory deficits were then investigated using the social recognition test. A significant amnesia was observed 4, 7 and 14 days after intraseptal injection of 3 nmol of beta (1-42), beta-(1-40)- and beta (25-35). Lower amounts of beta (1-42) were inactive except 1.5 nmol that disrupted memory 7 days post-treatment. Used as control, the inverted peptide beta (40-1) and the scrambled beta (25-35) were inactive. Using the prolongation procedure, rats infused with 3 nmol of beta (1-40) were still able to recognize the same juvenile. Finally, a daily treatment with the non-peptide neurotrophic compound SR 57746A (10 mg/kg p.o.) over 21 days, prevented the deficits in short-term memory induced by the intraseptal infusion of 3 nmol of either beta (1-40) or beta (25-35). These findings suggest that A beta fragments could impair short-term memory when infused in the rat medial septum, an effect that is prevented by SR 57746A.
Article
The present studies investigate the effects of early nerve growth factor (NGF) administration on the ontogenetic profile of learning and retention capacities in mice. The learning paradigm used required the animals to withhold an escape response from a vibrating platform to avoid a punishment (step-down passive avoidance). In Experiment 1, acquisition of step-down passive avoidance was essentially the same in 11- and 15-day-old mice whereas only the latter showed significant retention after 24 h. In younger animals, data pointed to a facilitating effect of familiarization with the test environment. In Experiment 2 ICV NGF treatment on postnatal day 9 increased step-down latencies in both reinforced and nonreinforced pups on day 11. Moreover, NGF mice exposed in nonreinforcement condition on day 11 failed to acquire the avoidance response 24 h later, suggesting that the treatment anticipated the appearance of latent inhibition. Results of Experiment 3, investigating the effects of different durations of preexposure to the test apparatus on passive avoidance acquisition 24 h later, supported the specificity of NGF effects on the emergence of latent inhibition. These findings suggest that neural populations responsive to NGF trophic effect are involved in the maturation of early learning and retention capacities in rodents.
Article
Novel diterpenoids, erinacines H (1) and I (3), were isolated from the cultured mycelia of Hericium erinaceum. The structures of the compounds were determined by interpretation of the spectral data. Erinacine H showed stimulating activity of nerve growth factor (NGF)-synthesis.
Article
It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid ??-peptide (A??) in plaques in brain tissue. According to the amyloid hypothesis, accumulation of A?? in the brain is the primary influence driving AD pathogenesis. The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between A?? production and A?? clearance.
Article
Phenotypic knockout of nerve growth factor (NGF) activity in transgenic anti-NGF mice (AD11 mice) results in a progressive neurodegenerative phenotype resembling Alzheimer's disease. In this article, we examine whether and how the progressive neurodegenerative phenotype of AD11 mice could be prevented or ameliorated by pharmacological treatments with NGF or the cholinergic agonist galantamine, at a relatively early phase of Alzheimer's disease-like neurodegeneration. We demonstrate that the neurodegeneration induced by the expression of anti-NGF antibodies in AD11 mice can be largely reversed by NGF delivery through an olfactory route.
Article
There are various neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and interleukin-6 (IL-6), which are essential for the promotion of neuronal survival (prevention of apoptosis), differentiation and regeneration in the central nervous system. Neurotrophic factors, neurotrophic factor-like substances and inducers of neurotrophic factor biosynthesis have enormous therapeutic potential for serious neuronal diseases such as Alzheimer's disease or traumatic, chemical and ischemic lesions in the brain. The clarification of the mechanism in neurotrophic factor biosynthesis is important in understanding the development of the drugs that stimulate neurotrophic factor production. In this review, we describe these mechanisms in the biosynthesis of NGF, BDNF, GDNF and IL-6, and also discuss the drugs that could possibly promote neurotrophic factor biosynthesis. (c) 2002 Prous Science. All rights reserved.
Article
Three isoforms of a vesicular glutamate transporter (VGLUT1-3) have been identified. Of these, VGLUT1 is the major isoform in the cerebral cortex and hippocampus where it is selectively located on synaptic vesicles of excitatory glutamatergic terminals. Variations in VGLUT1 expression levels have a major impact on the efficacy of glutamate synaptic transmission. Given evidence linking alterations in glutamate neurotransmission to various neuropsychiatric disorders, we investigated the possible influence of a down-regulation of VGLUT1 transporter on anxiety, depressive-like behaviour and learning. The behavioural phenotype of VGLUT1-heterozygous mice (C57BL/6) was compared to wild-type (WT) littermates. Moreover, VGLUT1-3 expression, hippocampal excitatory terminal ultrastructure and neurochemical phenotype were analysed. VGLUT1-heterozygous mice displayed normal spontaneous locomotor activity, increased anxiety in the light-dark exploration test and depressive-like behaviour in the forced swimming test: no differences were shown in the elevated plus-maze model of anxiety. In the novel object recognition test, VGLUT1(+/-) mice showed normal short-term but impaired long-term memory. Spatial memory in the Morris water maze was unaffected. Western blot analysis confirmed that VGLUT1 heterozygotes expressed half the amount of transporter compared to WT. In addition, a reduction in the reserve pool of synaptic vesicles of hippocampal excitatory terminals and a 35-45% reduction in GABA in the frontal cortex and the hippocampus were observed in the mutant mice. These observations suggest that a VGLUT1-mediated presynaptic alteration of the glutamatergic synapses, in specific brain regions, leads to a behavioural phenotype resembling certain aspects of psychiatric and cognitive disorders.