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Improvement of cognitive functions by oral intake of Hericium erinaceus
Abstract
Hericium erinaceus has been recognized as medical mushroom since ancient time, but its scientific evidence for human health has been still uncertain. In this study, we tested a randomized, double-blind, placebo-controlled parallel-group comparative study to evaluate the improvement of the cognitive functions by taking supplements containing fruiting body of H. erinaceus for 12 weeks. We performed three kinds of tests: Mini Mental State Examination (MMSE), Benton visual retention test, and Standard verbal paired-associate learning test (S-PA). MMSE alone showed that oral intake of H. erinaceus significantly improved cognitive functions and prevented from the deterioration. We speculate that various chemical compounds, including hericenones, in the mushroom have multiple effects to the brain neural networks and improve cognitive functions. Oral intake of H.erinaceus is safe and convenient method for dementia prevention so far.
... Several studies involving animal models and human subjects suggest that bioactive compounds in H. erinaceus have neuroprotective activities [14,[20][21][22]. Therefore, extracts and isolated compounds from this mushroom species attract a lot of interest in terms of Figure 5. ...
... Several studies involving animal models and human subjects suggest that bioactive compounds in H. erinaceus have neuroprotective activities [14,[20][21][22]. Therefore, extracts and isolated compounds from this mushroom species attract a lot of interest in terms of restorative and preventative care for neurodegenerative diseases. ...
... Therefore, extracts and isolated compounds from this mushroom species attract a lot of interest in terms of restorative and preventative care for neurodegenerative diseases. Cognitive functions were found to be improved in elderly human subjects given H. erinaceus supplements containing dried powder of the fruiting bodies [20,23]. An important consideration while interpreting the health benefits of bioactive compounds is their bioavailability upon consumption or administration into the human body. ...
Hericium erinaceus, a mushroom species commonly known as Yamabushitake in Japan, is known to have a stimulatory effect on neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Hericenone C, a meroterpenoid with palmitic acid as the fatty acid side chain, is reported to be one such stimulant. However, according to the structure of the compound, the fatty acid side chain seems highly susceptible to lipase decomposition, under in vivo metabolic conditions. To study this phenomenon, hericenone C from the ethanol extract of the fruiting body was subjected to lipase enzyme treatment and observed for changes in the chemical structure. The compound formed after the lipase enzyme digestion was isolated and identified using LC-QTOF-MS combined with 1H-NMR analysis. It was found to be a derivative of hericenone C without its fatty acid side chain and was named deacylhericenone. Interestingly, a comparative investigation of the neuroprotective properties of hericenone C and deacylhericenone showed that the BDNF mRNA expression in human astrocytoma cells (1321N1) and the protection against H2O2-induced oxidative stress was considerably higher in the case of deacylhericenone. These findings suggest that the stronger bioactive form of the hericenone C compound is in fact deacylhericenone.
... In particular, in vivo investigation in mouse models revealed that erinacine A in the mycelia confers nootropic effects and reduces oxidative stress against stroke [46], AD [69], depression [70], and aging [71]. On the other hand, the neuroprotective role played in vivo by hericenones from the H. erinaceus sporophores is still controversial, even though oral sporophore supplementation exerted a nootropic action in pilot clinical trials, as reported in the Section 8 [72][73][74]. Nonetheless, few studies have been conducted thus far on the bioavailability and tissue distribution of these relatively hydrophobic metabolites with a low molecular weight. ...
... A pilot interventional study was conducted on 31 subjects over 50 years old that were healthy, and with normal cognitive functions after H. erinaceus oral administration. The dry powder of H. erinaceus sporophore (0.8 g four times a day, for 12 weeks) was tested in this randomized, double-blind placebo-controlled parallel-group comparative study [74]. Three different tests were used to assess the effects of H. erinaceus on cognitive functions: Mini Mental State Examination (MMSE), standard verbal-paired-associate learning test, and Benton visual retention. ...
... Timeline of the published papers relating the effects of H. erinaceus in clinical studies[72][73][74]85,86,124,127]. ...
A growing number of studies is focusing on the pharmacology and feasibility of bioactive compounds as a novel valuable approach to target a variety of human diseases related to neurological degeneration. Among the group of the so-called medicinal mushrooms (MMs), Hericium erinaceus has become one of the most promising candidates. In fact, some of the bioactive compounds extracted from H. erinaceus have been shown to recover, or at least ameliorate, a wide range of pathological brain conditions such as Alzheimer’s disease, depression, Parkinson’s disease, and spinal cord injury. In a large body of in vitro and in vivo preclinical studies on the central nervous system (CNS), the effects of erinacines have been correlated with a significant increase in the production of neurotrophic factors. Despite the promising outcome of preclinical investigations, only a limited number of clinical trials have been carried out so far in different neurological conditions. In this survey, we summarized the current state of knowledge on H. erinaceus dietary supplementation and its therapeutic potential in clinical settings. The bulk collected evidence underlies the urgent need to carry out further/wider clinical trials to prove the safety and efficacy of H. erinaceus supplementation, offering significant neuroprotective applications in brain pathologies.
... For example, HE has continuously demonstrated properties to stimulate nerve growth factor and brain-derived neurotropic factor production, both which are known to increase cognitive functioning through its neurotrophic properties (5, 19). Interestingly, only four studies to date have examined the psychological, gut microbiota, and neuroprotective effects of HE in humans and findings are mixed (19,20,27,30). While data are limited in both animals and humans, discrepancies in findings likely reflect the incorporation of an absolute versus a relative HE dose (grams vs. mg/kg), the dose incorporated for HE consumption (~50 mg/kg -4 g/day), and the duration of HE consumption (2-16 weeks), Additionally, no studies have yet examined HE consumption on markers of metabolic flexibility or cognitive performance in a human cohort. ...
... The DTC consisted of three consecutive 15-s segments composed of two visual-verbal modified Stroop Color Word (SCW; 11) interposed by a mental arithmetic task (MAT). Participants simultaneously completed a Y-Balance Test (YBT) during the DTC (27). The cognitive component of this protocol (i.e., SCW and MAT) was adopted from previous investigations (1,17,28) and modified to be performed during the YBT. ...
... At present, there are only four studies examining the effects of HE in humans focused on aspects of cognition such as depression and anxiety (20) or the effect of HE on the progression of Alzheimer's disease (15,19,27). Our study is unique in that it tested HE supplementation on markers of cognitive performance as opposed to markers of cognitive decline (e.g., dementia). ...
Hericium erinaceus (HE), also known as Lion's Mane mushroom, has been found to enhance cognition and metabolic flexibility in various animal models. To date however, only four studies exist in humans and none have evaluated the effects of HE on markers of metabolic flexibility or cognitive performance. A single-blind, placebo controlled, parallel-longitudinal study was used to determine the effects of HE on markers of metabolic flexibility and cognition. Twenty-four participants completed a graded exercise test on a cycle ergometer to analyze substrate oxidation rates and markers of cardiorespiratory fitness. Additionally, two dual-task challenges consisting of a Stroop Word Challenge interspersed with a Mental Arithmetic Challenge were performed, pre-post the graded exercise test, to evaluate markers of cognition in a pre-post fatigued state. Participants were stratified into two groups, receiving either 10 g of HE per day or placebo for 4-weeks in the form of two muffins identical in taste and appearance. Repeated-measures analysis of variance were conducted to evaluate potential interactions or main effects. Although group differences were noted at baseline, there were no significant interactions or main effects observed from HE ingestion for any dependent variable (all p > 0.05). Our data suggest that ingesting 10 g of HE per day for 4-weeks had no impact on metabolic flexibility and cognition in a college-age cohort. Due to the limited research on HE supplementation, future research is needed to establish an effective supplement dose and duration for potential physiological changes to be observed in humans.
... A 12-week parallel intervention study in 31 cognitively healthy adults allocated to consume either a combination of an extract of Eleutherococcussenticosus (ES) and rhizomes of Drynariafortunei (DR) (203.01 mg/d of ES leaf extract, and 20.01 mg/d of DR), showed significant improvements in language, semantic fluency and figure recall scores [75]. Consumption of Hericiumerinaceus supplement (3.2 g/d) for 12 weeks also improved cognitive function and prevented cognitive decline in a study of 34 cognitively healthy subjects over the age of 50 years [76]. The effect of fermented Laminaria japonica was also evaluated in 60 moderately active senior subjects randomized to consume either 1.5 g/d of this supplement or a sucrose pill as placebo. ...
... Other dietary supplements that have shown significant improvements on different cognitive domains are fungi and algae extracts (Hericiumerinaceus, Tremella fuciformis and Laminaria japonica), other plant extracts (Eleutherococcussenticosus leaf, Drynariafortuneirhizome, combined sage, rosemary and melissa, auraptene, astaxanthin and matured hop bitter acids), minerals such as magnesium, medium-chain triglycerides and the complex Twendee X (supplement containing a mix of eight antioxidants). The consumption of the above antioxidant and anti-inflammatory supplements not only significantly improved subjective memory complaints [84] and scores in different cognitive domains such as psychomotor and processing speed [73], working memory [76,77,79,81], short-term memory [74,76,77,84], spatial working memory [75,79,81,87], verbal episodic memory [78], verbal fluency [75,82,83], language [75,79,81,87], executive functions [79,82,84] and attention [79,83,87], but also cortical gray matter integrity in AD-related brain regions [84]. The spermidine-rich plant extract also had an impact on memory performance in subjects with SCD, although this was not significant, probably due to the small sample size (n = 30) and/or the short follow-up period (3 months) [85]. ...
... Other dietary supplements that have shown significant improvements on different cognitive domains are fungi and algae extracts (Hericiumerinaceus, Tremella fuciformis and Laminaria japonica), other plant extracts (Eleutherococcussenticosus leaf, Drynariafortuneirhizome, combined sage, rosemary and melissa, auraptene, astaxanthin and matured hop bitter acids), minerals such as magnesium, medium-chain triglycerides and the complex Twendee X (supplement containing a mix of eight antioxidants). The consumption of the above antioxidant and anti-inflammatory supplements not only significantly improved subjective memory complaints [84] and scores in different cognitive domains such as psychomotor and processing speed [73], working memory [76,77,79,81], short-term memory [74,76,77,84], spatial working memory [75,79,81,87], verbal episodic memory [78], verbal fluency [75,82,83], language [75,79,81,87], executive functions [79,82,84] and attention [79,83,87], but also cortical gray matter integrity in AD-related brain regions [84]. The spermidine-rich plant extract also had an impact on memory performance in subjects with SCD, although this was not significant, probably due to the small sample size (n = 30) and/or the short follow-up period (3 months) [85]. ...
New dietary approaches for the prevention of cognitive impairment are being investigated. However, evidence from dietary interventions is mainly from food and nutrient supplement interventions, with inconsistent results and high heterogeneity between trials. We conducted a comprehensive systematic search of randomized controlled trials (RCTs) published in MEDLINE-PubMed, from January 2018 to July 2021, investigating the impact of dietary counseling, as well as food-based and dietary supplement interventions on cognitive function in adults with or without cognitive impairment. Based on the search strategy, 197 eligible publications were used for data abstraction. Finally, 61 articles were included in the analysis. There was reasonable evidence that dietary patterns, as well as food and dietary supplements improved cognitive domains or measures of brain integrity. The Mediterranean diet showed promising results, whereas the role of the DASH diet was not clear. Healthy food consumption improved cognitive function, although the quality of these studies was relatively low. The role of dietary supplements was mixed, with strong evidence of the benefits of polyphenols and combinations of nutrients, but with low evidence for PUFAs, vitamin D, specific protein, amino acids, and other types of supplements. Further well-designed RCTs are needed to guide the development of dietary approaches for the prevention of cognitive impairment.
... To date, studies in this demographic are limited and often target healthy, older adults or assess mood effects in isolation. Here, improved scores on the Mini-Mental State Examination have been observed in adults aged ≥50 years who consumed 3.2 g of powdered fruiting body daily for 12 weeks [22], although no additional effects were observed on other measures. Most recently, a trial in a college-age athlete cohort aimed to assess the cognitive effects of 4-week H. erinaceus supplementation (10 g/day, presented in muffin form) [23]. ...
... This includes a previous trial in healthy, young adults, where no effects were observed on Stroop task performance when presented as a dual task challenge [23]. Therefore, this is the first study to demonstrate cognitive benefits of H. erinaceus in a young, healthy sample following a single dose of H. erinaceus, thus adding to the growing body of literature which has shown cognitive improvements following chronic supplementation in older adults with diagnosed mild cognitive impairment [20] and mild Alzheimer's disease [21] and no cognitive impairments [22]. When considering mechanisms that may underlie this effect, it is well established that BDNF regulates synaptic plasticity and processes related to learning and memory consolidation [35]; however, there is less evidence pertaining to other areas of cognitive function. ...
Background: Given the bioactive properties and limited work to date, Hericium erinaceus (Lion’s mane) shows promise in improving cognitive function and mood. However, much of the human research has concentrated on chronic supplementation in cognitively compromised cohorts. Objective: The current pilot study investigated the acute and chronic (28-day) cognitive and mood-enhancing effects of Hericium erinaceus in a healthy, young adult cohort. Design: This randomized, double-blind, placebo-controlled, parallel-groups design investigated the acute (60 min post dose) and chronic (28-day intervention) effects of 1.8 g Hericium erinaceus in 41 healthy adults aged 18–45 years. Results: Analysis revealed that following a single dose of Hericium erinaceus, participants performed quicker on the Stroop task (p = 0.005) at 60 min post dose. A trend towards reduced subjective stress was observed following 28-day supplementation (p = 0.051). Conclusions: The findings tentatively suggest that Hericium erinaceus may improve speed of performance and reduce subjective stress in healthy, young adults. However, null and limited negative findings were also observed. Given the small sample size, these findings should be interpreted with caution. Further investigation in larger sample sizes is crucial, however the findings of this trial offer a promising avenue of interest.
... A study of subjects (n = 30) aged between 50 and 80 years with MCI who took 3000 mg of Lion's Mane powder per day for 16 weeks showed improved cognitive function on the Revised Hasegawa Dementia Scale compared to placebo [87]. A subsequent trial showed that healthy subjects (n = 31) with a mean age of 61 years and baseline MMSE (29.19 vs 28.73, p = 0.46) who took 3200 mg per day for 12 weeks significantly increased MMSE compared to placebo (30.00 vs 29.53, p = 0.03) [88]. The most recent trial provided more longitudinal data at a lower dose, with 1050 mg per day for 49 weeks, in mild AD subjects (n = 49) with a mean age of 74 years and baseline MMSE (21.8 vs 21.3, p = 0.6), which showed significantly increased MMSE scores compared to placebo (23.2 vs 20.7, p = 0.035) [89]. ...
... A comprehensive workup was done, and no differences were found between the rats treated with Lion's Mane and the control group [90]. The three RCTs on Lion's Mane that have been conducted so far with dosages ranging from 1050 mg to 3200 mg per day have noted rare and minimal side effects, including nausea, abdominal discomfort, and skin rash [87][88][89]. ...
In 2021, the Global Brain Health Supplement Industry Market size was valued at US$7.6 billion. It is predicted to increase to US$15.59 billion by 2030. Memory and its enhancement are a segment of the market that comprised the highest global revenue share in 2021. In the USA alone, dietary supplement sales reached US$18 billion in 2018. The US Food and Drug Administration (FDA) does not have the authority to approve dietary supplements' safety, effectiveness, or labeling before products go on the market. The FDA often does not even review supplements before they go to market. Supplement manufacturers are thus responsible for ensuring their products are safe and that their claims are truthful. An extensive review of current supplements on the market was performed by surveying memory products for sale at local and national pharmacies and grocery stores. A list of 103 supplements was compiled and the ingredients in these memory supplements were reviewed. The 18 most common ingredients in these supplements were identified. Each of the supplements included at least one of the 18 most common ingredients. Scientific data relative to these ingredients and their effect on memory was searched using PubMed and Cochrane library databases. Currently, there is no compelling evidence for use of apoaequorin, coenzyme Q10, coffee extracts, L-theanine, omega-3 fatty acids, vitamin B6, vitamin B9, or vitamin B12 supplementation for memory. On the other hand, there is some current evidence for memory benefit from supplementation with ashwagandha, choline, curcumin, ginger, Lion's Mane, polyphenols, phosphatidylserine, and turmeric. There are current studies with mixed results regarding the benefit of carnitine, gingko biloba, Huperzine A, vitamin D, and vitamin E supplementation for memory. Dietary supplements geared toward improving cognition are a billion-dollar industry that continues to grow despite lacking a solid scientific foundation for their marketing claims. More rigorous studies are needed relative to the long-term use of these supplements in homogenous populations with standardized measurements of cognition. Health care providers need to be aware of any and all supplements their older adult patients may be consuming and be educated about their side effects and interactions with prescription medications. Lastly, the FDA needs to take an active position relative to monitoring marketed supplements regarding safety, purity and claims of efficacy.
... Another study noted improvements in attention and memory in healthy medical students from taking 150mg of Bacopa Monnieri for six weeks [12]. Other ingredients in Mind Lab Pro such as Lion's Mane Mushroom, Tyrosine and Phosphatidylserine has also been found to improve memory and attention in a variety of contexts for a range of healthy and unhealthy populations [13][14][15][16]. Reductions in fatigue and stress have also been found in studies looking at the impact of taking Rhodiola Rosea in healthy populations [17,18] as well as cognitive improvements in adults with physical and cognitive difficulties [19]. ...
... It was encouraging to see this in older participants as this has also been shown by other studies [48]. Citicoline, Bacopa Monnieri, Lion's Mane Mushroom, Tyrosine and Phosphatidylserine taken in combination have been shown to with improve focus and attention which is important when performing choice reaction type tasks [8,12,13,15]. The vitamins in Mind Lab Pro have also been shown to improve cognitive functioning especially in older populations [23,25,26]. ...
... Recently, Saitsu et al. showed that oral intake of HE by humans improved cognitive functions and prevented neuronal deterioration. It is speculated that hericenones, one of the chemical compounds of this mushroom, have multiple effects on the brain neural networks and improve cognitive functions [9]. However, so far, only a few studies have investigated its use in mental disorders, and either each study only focused on a specific psychiatric disorder or these studies have established a direct causal relationship between exposure and outcome. ...
... Saitsu et al. [9] realized a randomized, parallel-group comparative, double-blind, placebo-controlled study. The 31 participants showed cognitive impairment, all the participants were over 50 years old (average in HE 61.8 and in placebo 60.8), and ingested, for 12 weeks, 3.2g/day of HE. ...
Introduction: Hericium erinaceus (HE), often known as Lion's Mane, is an edible fungus that has been extensively explored for its many functions. The use of this mushroom in traditional Chinese medicine dates back many years, and it is now being tested in the treatment of cognitive decline and Alzheimer's disease, and mental diseases like depression, anxiety, schizophrenia. Methods: We followed 2020 PRISMA statement for systematic reviews. The three selected databases were Worldcat®, Cochrane Library®, and PubMed®. On March 7, 2022, a search for articles was conducted. The search sources' descriptions were Hericium erinaceus AND (mental disorders OR cognitive impairment OR depression OR anxiety). "English" was the sole filter applied to the data sources. Results: Three Japanese randomized double-blind controlled trials were included in the review. Although the data demonstrated that HE can be useful in treating symptoms of cognitive impairment and moderate cognitive impairment, it was not effective in treating depression/anxiety symptoms. Conclusions: More studies are needed in countries besides Japan, lasting at least 12 weeks, since shorter periods do not demonstrate significant improvement of symptoms. Incorporating HE into a patient's daily diet may produce favorable benefits by alleviating cognitive decline.
... The most recent study was a double-blind, parallel group clinical trial by Saitsu et al. examining the effects of the consumption of four HE supplements containing 0.8 g of powdered fruiting bodies daily for 12 weeks. Cognitive abilities were assessed by the Mini-Mental State Examination (MMSE), standard verbal paired-associate learning, and Benton visual retention tests [62]. The HE treatment was found to prevent short-term memory decline and improve cognitive function in the MMSE, indicating the beneficial effects on neural network regeneration and its overall safety. ...
... Erinacines A-I were demonstrated to have neuroprotective properties through enhancing the release of neurotrophic factors, increasing the expression of insulin-degrading enzymes (erinacines A and S), reducing Aβ aggregation, and managing neuropathic pain (erinacine E) (Figure 2) [63]. The majority of hericenones were demonstrated to have been correlated with improved cognitive function through the activation of NGF synthesis in astrocytes, whereas erinacine B was found to prevent thrombosis, increase cerebral blood flow, and confer protection against cerebrovascular risk and vascular dementia [62,64]. ...
Alzheimer’s disease (AD) is a neurodegenerative disorder, and no effective treatments are available to treat this disorder. Therefore, researchers have been investigating Hericium erinaceus, or the monkey head mushroom, an edible medicinal mushroom, as a possible treatment for AD. In this narrative review, we evaluated six preclinical and three clinical studies of the therapeutic effects of Hericium erinaceus on AD. Preclinical trials have successfully demonstrated that extracts and bioactive compounds of Hericium erinaceus have potential beneficial effects in ameliorating cognitive functioning and behavioral deficits in animal models of AD. A limited number of clinical studies have been conducted and several clinical trials are ongoing, which have thus far shown analogous outcomes to the preclinical studies. Nonetheless, future research on Hericium erinaceus needs to focus on elucidating the specific neuroprotective mechanisms and the target sites in AD. Additionally, standardized treatment parameters and universal regulatory systems need to be established to further ensure treatment safety and efficacy. In conclusion, Hericium erinaceus has therapeutic potential and may facilitate memory enhancement in patients with AD.
... Du ring another study conducted in 2019 the participants ate cakes containing the Lion's mane during a 3 months' period. The results of this experiment show ed an improvement of cognitive functions and a significant inhibition of short-term memory disorders [25]. The fact that the Lion's mane contains active chemical compounds stimulating production of nerve growth factor (NGF), is well known [26]. ...
... W innym badaniu z 2019 roku uczestnicy, przez okres 3 miesięcy, otrzymywali ciastka zawierające Lwią grzywę. Wyniki przeprowadzonego eksperymentu wykazały poprawę funkcji poznawczych oraz istotne zahamowanie zaburzeń pamięci krótkotrwałej [25]. Wiadomo, że Lwia grzywa zawiera aktywne związki, które stymulują produkcję czynnika wzrostu nerwów (NGF) [26]. ...
Physically active people and athletes always seek new dietary interventions including natural products, hoping to improve their condition and gain support, allowing them to meet their settled goals. Potential benefits of using medicinal mushrooms (ganotherapy), resulting from their proven efficacy, seem extremely promising for athletic performance. They may evoke a justified interest, especially among competitors from western countries where the tradition of using mushrooms for health reasons is virtually nonexistent. The goal of the paper is to present the current knowledge of selected medicinal mushrooms among the population involved in excessive physical exercise and the range of research in the above-mentioned domain.
... In a more recent double-blind, placebo-controlled study assessing the effect of lion's mane on cognitive function, healthy older adults over 50 years of age (n=31) were randomized for 12 weeks to either 4 times/day dose of 0.8 g of lion's mane (3.2 g/day total; n=16) or placebo (n=15) [67]. Cognitive function was assessed at baseline and 6 and 12 weeks using the MMSE, the Benton visual retention test, and the Standard verbal paired-associate learning test. ...
... In addition to various diseases and disorders, nutrients and phytonutrients have been examined for their efficacy on cognitive function in healthy adults. For example, Bacopa monnieri has been studied in a few instances in healthy populations of various ages and shows promise in improving several domains of cognitive function with minimal recorded adverse effects [35,[37][38][39][40]. Lion's mane also showed a significant improvement in cognitive function in older adults after 12 weeks of consumption [67]. Furthermore, Rhodiola rosea has shown hopeful results in improving mental capacity for work, fatigue, anxiety, mood, and cognitive performance in healthy adults [194][195][196][197][198]. ...
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.
... Recent studies focus on the pharmacology and feasibility of bioactive compounds of plant and fungal origin as a potential strategy to target a variety of human metabolic and brain disorders [37]. The mechanism and possible synergy of action of these compounds has not been studied yet, however mushrooms-derived products with potential neuroprotective and psychotropic activities can prevent and mitigate development of mental disorders, including depression, anxiety, sleep disturbances and cognitive alterations [1, 7, 8, 12-14, 20, 21-24]. ...
... The cultivated edible mushroom, H. erinaceus is an important medicinal fungus with immunomodulatory, anti-mutagenic, antioxidant, anti-inflammatory and antitumor properties. Myco-pharmacological studies have attracted considerable attention on H. erinaceus as a neuroprotector to prevent NDD, including dementia, anxiety or depression [7,13,20,25,[35][36][37][38]. ...
Badalyan S.M. et Rapior S. Agaricomycetes medicinal mushrooms with potential potential neuroprotective activity growing in rmenia.
Proceedings of the Yerevan State University, Chemistry and Biology, 54 (3), 196-203 (2020). hal-03090953 _____ The Agaricomycetes mushrooms (phylum Basidiomycota) are recognised sources of valuable food and medicines. They are producers of bioactive compounds (phenolics, polysaccharides, proteins, steroids, terpenoids, etc.) possessing around 130 therapeutic effects (antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, etc.). Mushrooms are also reported as potential
neurotrophic and neuroprotective agents. Seventeen edible and inedible agaricomycetous species from different taxonomic and ecological groups have been reported in Armenia to possess neuroprotective activity. Evaluation resource value and biotechnological potential of Armenian agaricomycetous mushrooms will assist further development of novel myco-pharmaceuticals to prevent and mitigate different disorders, including neurodegenerative.
... These results suggest the antidepressant effects of H. erinaceus, which is consistent with the findings of Nagano et al. [130], who showed that H. erinaceus supplementation led to a reduction in depression and anxiety in 30 women after 4 weeks of supplementation. Saitsu et al. [128] conducted a comparative study in which the consumption of cookies containing H. erinaceus for 12 weeks showed alleviation of symptoms of short-term memory impairment and improved cognitive function in 31 participants. ...
Hericium erinaceus is a valuable mushroom known for its strong bioactive properties. It shows promising potential as an excellent neuroprotective agent, capable of stimulating nerve growth factor release, regulating inflammatory processes, reducing oxidative stress, and safeguarding nerve cells from apoptosis. The active compounds in the mushroom, such as erinacines and hericenones, have been the subject of research, providing evidence of their neuroprotective effects. Further research and standardization processes for dietary supplements focused on H. erinaceus are essential to ensuring effectiveness and safety in protecting the nervous system. Advancements in isolation and characterization techniques, along with improved access to pure analytical standards, will play a critical role in achieving standardized, high-quality dietary supplements based on H. erinaceus. The aim of this study is to analyze the protective and nourishing effects of H. erinaceus on the nervous system and present the most up-to-date research findings related to this topic.
... For example, a double-blind placebo-controlled trial reported that intake of 250 mg tablets containing Hericium erinaceus for 16 weeks improved mild cognitive impairment in Japanese men 50-80 years old (151). Likewise, another double-blind placebo-controlled trial showed that consumption of Hericium erinaceus for 12 weeks improved cognitive functions (152). In contrast, a single-blind placebo longitudinal trial showed that intake of 10 g of Hercium erinaceus for four weeks had no impact on metabolic markers or cognition in younger adults (153). ...
Dementia is a growing public health concern, with an estimated prevalence of 57 million adults worldwide. Alzheimer's disease (AD) accounts for 60-80% of the cases. Clinical trials testing potential drugs and neuroprotective agents have proven futile, and currently approved drugs only provide symptomatic benefits. Emerging epidemiological and clinical studies suggest that lifestyle changes, including diet and physical activity, offer an alternative therapeutic route for slowing and preventing cognitive decline and dementia. Age is the single most common risk factor for dementia, and it is associated with slowing cellular bioenergetics and metabolic processes. Therefore, a nutrient-rich diet is critical for optimal brain health. Furthermore, type 2 diabetes (T2D) is a risk factor for AD, and diets that reduce the risk of T2D may confer neuroprotection. Foods predominant in Mediterranean, MIND, and DASH diets, including fruits, leafy green vegetables, fish, nuts, and olive oil, may prevent or slow cognitive decline. The mechanisms by which these nutrients promote brain health, however, are not yet completely understood. Other dietary approaches and eating regimes, including ketogenic and intermittent fasting, are also emerging as beneficial for brain health. This review summarizes the pathophysiology, associated risk factors, and the potential neuroprotective pathways activated by several diets and eating regimes that have shown promising results in promoting brain health and preventing dementia.
... Furthermore, enhanced expression of NGF was also detected in the hippocampus of ddY mice administrated with H. erinaceum extracts, and this was related to c-Jun N-terminal kinase (JNK) signaling [152]. After taking supplements containing H. erinaceum for 12 weeks, the cognitive functions of subjects undergoing clinical testing clearly improved [153]. In addition, during an investigation of isolating the metabolites of H. erinaceum, multiple hericenones and their analogs were obtained, such as hericenones C and D [154]. ...
Mushrooms with edible and medicinal potential have received widespread attention because of their diverse biological functions, nutritional value, and delicious taste, which are closely related to their rich active components. To date, many bioactive substances have been identified and purified from mushrooms, including proteins, carbohydrates, phenols, and vitamins. More importantly, molecules derived from mushrooms show great potential to alleviate the pathological manifestations of Alzheimer’s disease (AD), which seriously affects the health of elderly people. Compared with current therapeutic strategies aimed at symptomatic improvement, it is particularly important to identify natural products from resource-rich mushrooms that can modify the progression of AD. This review summarizes recent investigations of multiple constituents (carbohydrates, peptides, phenols, etc.) isolated from mushrooms to combat AD. In addition, the underlying molecular mechanisms of mushroom metabolites against AD are discussed. The various mechanisms involved in the antiAD activities of mushroom metabolites include antioxidant and anti-neuroinflammatory effects, apoptosis inhibition, and stimulation of neurite outgrowth, etc. This information will facilitate the application of mushroom-derived products in the treatment of AD. However, isolation of new metabolites from multiple types of mushrooms and further in vivo exploration of the molecular mechanisms underlying their antiAD effect are still required.
... Furthermore, its therapeutic potential has been demonstrated in several conditions, including diabetes, hyperlipidaemia, neurodegenerative disorders, and cancer [5][6][7][8]. In addition, mild cognitive impairment is another disorder in which H. erinaceus has shown encouraging results in randomised clinical trials [9,10]. ...
Hericium erinaceus is an edible and medicinal mushroom commonly used in traditional Chinese medicine for centuries. Several studies have highlighted its therapeutic potential for gastrointestinal disorders such as gastritis and inflammatory bowel diseases. In addition, some components of this mushroom appear to possess strong antineoplastic capabilities against gastric and colorectal cancer. This review aims to analyse all available evidence on the digestive therapeutic potential of this fungus as well as the possible underlying molecular mechanisms.
... Preclinical trials conducted from 2011 to 2021 successfully demonstrated that extracts and bioactive compounds obtained from H. erinaceus have beneficial effects in improving cognitive function and behavioral deficit in animal models (mice and rats) (Yanshree et al. 2022). Three double-blind placebo-controlled clinical studies have shown similar results to preclinical studies (Mori et al. 2009(Mori et al. , 2011Saitsu et al. 2019;Li et al. 2020). Nevertheless, future research on H. erinaceus should focus on elucidating specific neuroprotective mechanisms and target sites in Alzheimer's disease. ...
Several human diseases, such as diabetes, cancer, cardiovascular and neurodegenerative disorders, increasingly affect the adult population worldwide. Therefore, scientists have tried to discover new natural sources of medicines, especially from mushrooms, to prevent and treat these diseases. Wild mushrooms and mushrooms growing on solid media or in submerged cultures belong to a large number of genera (Agaricus, Auricularia, Ganoderma, Grifola, Hericium, Lentinula, Schizophyllum) and may be used to produce biologically active compounds (lectins, polysaccharides, phenolics, terpenoids, and steroid derivatives) as anti-inflammatory, antimicrobial, antioxidant, antitumor, antiviral, hepatoprotective, hypocholesterolemic, hypoglycemic, immunomodulatory, and neuroprotective agents. Metabolomics and genomic studies of the unexplored biotechnological potential of mushrooms may also assist in the production of mushroom-derived biotech products. High-quality, long-term, randomized, double-blind, placebo-controlled clinical studies have been described as necessary to prove the efficacy of mushroom extracts or isolated compounds. The present review discusses the current state of knowledge and the main findings of previous studies on mycotherapeutics and healthy mycofood. This chapter is an update contribution to modern mycopharmacology and biomedicine. Keywords: Biomedicine Clinical trials Mushrooms Mycopharmaceuticals Mycotherapy Nutraceuticals
... 17) Hericium erinaceus (HE) is known as Lion's Mane mushroom or yamabushitake in Japan. HE is a medicinal mushroom that has the potential for treating various conditions, including depression, anxiety, 18) neurodegenerative diseases, 19,20) dementia, cognitive impairment, [21][22][23] diabetes, 24) cancer, 25,26) and spinal cord injury. 27) It has also been shown to promote neurite outgrowth and nerve regrowth and to have a neuroprotective effect. ...
Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion’s Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17β-estradiol (E2) but not with HE. Thus, the phytoestrogens in HE may hardly activate ERα. Estrogen receptor beta (ERβ) is expressed in the brain, and activation of ERβ ameliorates menopausal depressive symptoms. Notably, depressive-like behavior in OVX rats evaluated in forced swim test was reduced by administration of not only E2 but also HE for 92 d. Long-term activation of ERα increases the risk of breast and uterine cancers. HE, therefore, may be effective in treating menopausal depression without the risk of carcinogenesis caused by ERα activation.
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... Wyniki testów były lepsze u osób stosujących soplówkę w porównaniu do grupy placebo. To wskazuje na możliwość udziału H. erinaceus w regeneracji sieci neuronalnych w dorosłym mózgu, choć jest to nadal przedmiotem dyskusji, czy neurony w obrębie ośrodkowego układu nerwowego posiadają zdolność regeneracji 10 . ...
Introduction:
Hericium erinaceus is a medicinal and culinary mushroom that is widely present in the countries of East Asia. Bioactive compounds derived from the fruiting body or its mycelium have many properties, including: antioxidant, antidiabetic, anti-inflammatory, as well as hypolipidemic properties. It also has the potential to treat neurological disorders as it contains neurotrophic compounds that can cross the blood-brain barrier.
Aim of the study: The aim of this work is to review scientific research on the potential properties of the H. erinaceus in treating diseases of the nervous system.
Results: Many studies have shown that Hericium erinaceus can bring the desired effects as a complementary treatment and be an alternative in the treatment of depressive and cognitive disorders and, due to its strong neuroprotective nature, be used in Alzheimer's disease or in post-traumatic brain injury. Most of the cited studies concern experiments carried out on animal models.
Conclusion: Due to the evidence of potentially neuroprotective properties of H. erinaceus, there is a need for further clinical trials in humans.
... Hericium erinaceus was found to have beneficial effects on cognition or mild cognitive impairment in several studies. 58,59 A combination of Ophiocordyceps sinensis and G. lucidum did not, however, enhance cognitive function in young healthy participants. 60 Psilocybin mushrooms have been studied mostly for their mind-altering properties, although they appear to have potential for the treatment of depression. ...
Mushrooms are valued by humans worldwide as food, but also for their medicinal properties. Over 130 medicinal effects of mushrooms have been reported, including anti-diabetic, antioxidant, antimicrobial, anticancer, prebiotic, immunomodulating, anti-inflammatory and cardiovascular benefits. Several mushrooms have been tested in phase I, II, or III clinical trials for various diseases, including cancers, as well as to modulate immunity. Here, we review clinical studies on medicinal mushrooms or preparations (but not pure compounds) derived thereof. Overall, few phase III trials have been performed, and in many cases, these trials included a relatively small number of patients. Therefore, despite the promising published clinical data, especially on immune modulation, more work is required to clarify the therapeutic value of mushrooms.
... 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). ...
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). ...
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
... Several clinical trials using the fruiting bodies of the fungus have demonstrated the antidementia effect of this fungus (Kasahara, Kaneko and Shimizu 2001;Mori et al. 2009;Nagano et al. 2010;Ohtomo, Shimizu and Komatsu 2011;Saitsu et al. 2019). Very recently, in order to investigate the efficacy and safety of mycelia of the fungus enriched with 5 mg/g erinacine A (7), a clinical trial study was conducted. ...
Hericium erinaceus (Yamabushitake in Japan) is a well-known edible and medicinal mushroom. We discovered antidementia compounds, hericenones C to H, from the fruiting bodies and erinacine A to I from the cultured mycelia of the fungus. Based on the data of the compounds, several clinical experiments were performed using the fungus. “Fairy rings” is a phenomenon that turfgrass grows more prolific or inhibited than the surrounding area as a ring and then occasionally mushrooms develop on the ring. We found fairy-ring causing principles “fairy chemicals” and the biosynthetic routes of the compounds on the purine metabolic pathway in plants and mushrooms.
... Recently, in a randomized, double-blind, placebo-controlled parallel-group, comparative study, the administration of a supplement containing Lion's mane mushroom fruiting body showed improvement of Mini-Mental State Examination (MMSE) scores among 16 healthy participants over 50 years old in the intervention group, compared with 15 participants in the placebo group (p = 0.0328) (Saitsu et al., 2019). However, Benton visual retention test and Standard verbal paired-associate learning test (S-PA) scores were not statistically different in the intervention group compared with placebo during follow up (ad-interim and ex-post) of 12 weeks. ...
Background
mushrooms are traditionally used as a food ingredient and in folk medicine. Many in vitro and animal studies have reported their potential health effects, but without any clear application in human health. Although they have a worldwide history of use in dishes and folk medicine, mushroom extracts are commonly taken as supplements but need to be evaluated regarding clinical effects and safety, in particular among patients searching for further efficacy for their disease beside pharmacological treatments already prescribed.
Scope and approach
this review summarizes available data from the scientific literature about the nutritional and effects of mushrooms on human health by selecting clinical studies on humans in English. At the same time, the safety profile and unwanted effects were highlighted.
Key findings and conclusions
in spite of their wide use among populations, data on humans were scant and did not justify extensive use without more well-designed trials on mushroom efficacy. Overall, their use seems to be safe, but with some side effects, easily reversible after intake interruption. Nutritional use seems promising for coping with the energy surplus of the Western countries and could be useful for some nutritional aspects.
... In another randomized, double-blind placebo-controlled study, administration of 0.5 g H. erinaceus fruiting body in cookies over 4 weeks showed a reduction in anxiety and depression in menopausal women (n = 30) compared to those taking placebo, as measured by the Center for Epidemiologic Studies Depression Scale and Indefinite Complaints Index (Nagano et al., 2010). In the third randomized, double-blind, placebo-controlled parallelgroup comparative study, the consumption of cookies containing 0.8 g of H. erinaceus fruiting body dry powder alleviated the deterioration of short memories and improved the cognitive functions in 31 participants with an average age of 61.3 years old over the period of 12 weeks, as measured by MMSE (Saitsu et al., 2019). Prior studies have reported that NGF could enhance neurogenesis-inducing effects, which led to antidepressant and antianxiety activities (Shohayeb et al., 2018). ...
Objective
To investigate the efficacy and safety of three H. erinaceus mycelia (EAHE) capsules (350 mg/capsule; containing 5 mg/g erinacine A active ingredient) per day for the treatment of patients with mild Alzheimer’s Disease (AD).Methods
This study comprised a 3-week no-drug screening period, followed by a 49-week double-blind treatment period with 2-parallel groups in which eligible patients were randomized to either three 5 mg/g EAHE mycelia capsules per day or identical appearing placebo capsules. Cognitive assessments, ophthalmic examinations, biomarker collection, and neuroimaging were followed throughout the study period.ResultsAfter 49 weeks of EAHE intervention, a significant decrease in Cognitive Abilities Screening Instrument score was noted in the placebo group, a significant improvement in Mini-Mental State Examination score was observed in the EAHE group and a significant Instrumental Activities of Daily Living score difference were found between the two groups. In addition, EAHE group achieved a significantly better contrast sensitivity when compared to the placebo group. Moreover, only the placebo group observed significantly lowered biomarkers such as calcium, albumin, apolipoprotein E4, hemoglobin, and brain-derived neurotrophic factor and significantly elevated alpha1-antichymotrypsin and amyloid-beta peptide 1–40 over the study period. Using diffusion tensor imaging, the mean apparent diffusion coefficient (ADC) values from the arcuate fasciculus region in the dominant hemisphere significantly increased in the placebo group while no significant difference was found in the EAHE group in comparison to their baselines. Moreover, ADC values from the parahippocampal cingulum region in the dominant hemisphere significantly decreased in the EAHE group whereas no significant difference was found in the placebo group when compared to their baselines. Lastly, except for four subjects who dropped out of the study due to abdominal discomfort, nausea, and skin rash, no other adverse events were reported.Conclusion
Three 350 mg/g EAHE capsules intervention for 49 weeks demonstrated higher CASI, MMSE, and IADL scores and achieved a better contrast sensitivity in patients with mild AD when compared to the placebo group, suggesting that EAHE is safe, well-tolerated, and may be important in achieving neurocognitive benefits.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04065061.
... Moreover, confirm the safety of H.erinaceous and could be used in dementia prevention. 5 Another recent Italian study in 2019 on mice reported that two-month of oral intake of H.erinaceous reversed the decline of age and restore cognition memory, which means this mushroom could have neurogenesis effect. 6 In line with a vitro study conducted in Malaysia showed that Lion's Mane mushrooms contain neurotrophic factors (hericenones and erinacines) which might induce nerve growth factors essential for the maintenance of optimum neural body structure to operate. ...
O cogumelo juba de leão (Hericium ERINACEUS) é um basidiomiceto da família Hericiae, de origem chinesa, sendo amplamente utilizado na medicina tradicional oriental. O objetivo do presente estudo é de evidenciar a eficácia e os benefícios farmacológicos e fisiológicos que esse cogumelo possui, destacando o seu potencial de melhorar a capacidade mental, o foco, a memória, e também de possibilitar um avanço na qualidade de vida de quem faz uso, reduzindo assim a probabilidade de síndromes demenciais. Sendo assim, este trabalho se trata de uma revisão bibliográfica descritiva, sendo utilizada para a pesquisa as bases de dados: Pubmed/Medline e Google Acadêmico, totalizando 6 artigos. Diante do exposto, o fator de crescimento neuronal (NGF) é a substância responsável pelas propriedades terapêuticas desse cogumelo, que em maior parte, possui a capacidade de ultrapassar a barreira hematoencefálica, favorecendo o crescimento de fibras neurais e reduzindo o stress oxidativo. Por fim, essa substância possui um grande potencial neuroprotetor e adaptogênico, com o potencial tóxico mínimo, o que garante que seja bem tolerado na maioria das pessoas e categórico do ponto de vista terapêutico. Vários estudos, com resultados satisfatórios, já evidenciaram os seus efeitos e repercussões nas disfunções cognitivas e em problemas de memória. O seu uso, quando bem indicado por um profissional habilitado, potencializa os seus efeitos no paciente, promovendo uma elevação na qualidade de vida.
Low mental energy can contribute to decreased productivity, altered life balance, decreased physical performance, and ultimately affect quality of life. As such, there is a great demand for food and beverage products that positively impact mental energy. Numerous products claim to alter mental energy making continued review of the scientific evidence critical. The objective of this study was to conduct a scoping review of randomized controlled trials to evaluate the effect of 18 dietary ingredients on mental energy outcomes in adults without severe disease. Methods: A literature search, completed using PubMed, resulted in the identification of 2261 articles, 190 of which met eligibility from initial abstract review. Full-text review was completed on the 190 studies which resulted in 101 articles that fully met eligibility for inclusion in this study. The search strategy for two ingredients did not yield any eligible studies, leaving studies for 16 ingredients that were extracted and summarized by reported significantly improved outcomes for cognition, mood and perceived feelings, and sleep assessments. The preliminary results for several dietary ingredients directionally suggested a mental energy benefit (≥20% of outcomes), including ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, tart cherries, turmeric, and valerian root. The results of this scoping review suggest that of the 16 dietary ingredients reviewed, 11 may be promising for further exploration on their potential benefits in supporting mental energy. Given consumer demand and market growth for food and beverage products that positively impact mental energy; continued efforts in assessment method alignment and additional evaluation in well-designed trials is warranted. KEY TEACHING POINTSOf the 16 dietary ingredients reviewed, 11 (ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, melatonin foods, turmeric, and valerian root) may be promising for further exploration on their potential mental energy benefits.Dark chocolate, ginseng, ashwagandha, and lion's mane mushroom were the most promising ingredients for further evaluation in the cognition domain of the ingredients evaluated.Turmeric, maca, lavendar, and ashwagandha were the most promising ingredients for further evaluation in the mood and perceived feelings domain of the ingredients evaluated.Ashwagandha, chamomile, green tea, melatonin foods, valerian root were the most promising ingredients for further evaluation in the sleep domain of the ingredients evaluated.Additional, well-designed, consistent, clinical trials and systematic reviews are warranted as the challenge of heterogeneity in mental energy study design remains.
Background/Objectives: Bioactive compounds in mushrooms may protect the brain from neurodegeneration by inhibiting the production of amyloid-β and playing an antioxidant role. This study aimed to examine the associations of...
A doença de alzheimer (da) é uma doença neurodegenerativa grave caracterizada por declínio cognitivo e perda de memória. Esta revisão visa explorar o potencial terapêutico do hericium erinaceus, também conhecido como cogumelo juba de leão, no tratamento da da. Revisamos a fisiopatologia da da, as propriedades medicinais do h. Erinaceus e os estudos clínicos conduzidos para investigar sua eficácia.
Objectives:
This study aimed to investigate the efficacy of taking Mind Lab Pro, a plant-based nootropic on memory in a group of healthy adults. Auditory, visual, visual working memory, immediate and delayed recall (DR) were assessed.
Methods:
The study employed a pseudo randomised, double blinded, placebo-controlled design. A total of 49 healthy individuals completed the study with 36 in the experimental group and 13 in the control group. Participants ranged between 20 and 68 years with a mean age of 31.4 ± 14.4 years. Pre and post taking either the Mind Lab Pro supplement or placebo for 30 days. All participants completed the Wechsler Memory Scale Fourth UK Edition (WSM-IV UK).
Results:
We found that the experimental group significantly improved in all memory subtests assessed (p < 0.05) whilst the control group only significantly improved in auditory memory and immediate recall (p = 0.004 and p = 0.014 respectively). A significant difference in immediate and DR was also found between the control and experimental group (p = 0.005 and 0.034 respectively).
Conclusion:
The use of Mind Lab Pro for 4 weeks improves memory with the experimental group significantly improving in all sub areas of memory as assessed by the WSM-IV UK.
his book, as part of the "Natural Products Chemistry of Global Plants" series, describes in detail the health promoting wild edible and medicinal mushrooms specific to the Himilayas region. The focus of the book is to draw on the rich culture, folklore, and environment of the Upper Himilayas, which represents a scientifically significant region. The Himilayas has rich plant resources and a large diversity of plants and mushrooms, which can provide important health benefits as detailed throughout the text. Drawing attention to these mushrooms with detailed scientific descriptions may help in the awareness and in developing sustainable growth of these important resources.
Features:
Provides an opportunity to describe the wild edible and medicinal mushrooms from this scientifically significant region.
Represents a wider variety of mushrooms than previously published in other books.
Presents more content related to traditional uses, phytochemistry, pharmacology, distribution, processing, toxicology, conservation and future prospective of individual mushrooms.
The plants and mushrooms of the region are valuable resources not only to local populations but to those living outside the region.
Scientists are monitoring the rich Himalayan plant resources and the consequences of climate change on this precarious ecosystem.
Dementia, a form of neurodegenerative disease, is a chronic brain disorder that affects memory and learning. Oxidative stress and inflammation are believed to contribute to the pathogenesis of dementia, as an imbalance of oxidant-antioxidant/pro-inflammatory-anti-inflammatory cytokines homeostasis causes neuroinflammation and an increased rate of reactive oxygen species generation. Natural, medicinal mushrooms, enriched with antioxidants and anti-inflammatory properties, are growing popular as agents to provide beneficial neuronal health effects, such as inhibiting oxidative stress, protecting neuronal excitotoxicity, and boosting the human immune response. Mushrooms such as Hericium erinaceus and Coriolus versicolor have been demonstrated to improve cognitive function and prevent and reduce Alzheimer’s and Parkinson’s disease. The bioactive compounds in these mushrooms include erinacines, polyphenols, polysaccharopeptides, and terpenoids. Erinacine A, one of the main bioactive components, effectively reduces neurodegeneration and dementia and has no known adverse side effects. The mycelia are safe for oral consumption over an extended period and can be supplemented in a diet. This chapter summarizes current scientific information on the health properties of H. erinaceus and C. versicolor to contribute to prophylactic and therapeutic findings regarding neuroprotection against dementia.KeywordsAlzheimer’s Disease
Coriolus versicolor
Dementia
Hericium erinaceus
MushroomsNeurodegeneration
Age-related loss of function brings age-related disease, and therefore it is of primary importance to search for interventions that can help minimize detrimental symptoms people deal with in old age. Fungi have always been given a great deal of attention and reverence in traditional medical practices for their ability to minimize harmful symptoms of diseases. More recently, the role of fungi in influencing healthspan and lifespan is being directly studied in the lab. To treat animal model organisms with fungi-derived molecules, extractions from different life cycle stages of fungi are performed. This includes mycelium (the vegetative stage), sporocarps (the reproductive stage), or spores (the end product of the reproductive stage), and each stage provides a variety of bioactive compounds. These bioactive compounds include glycoproteins, polysaccharides, triterpenoids, meroterpenoids, sesquiterpenoids, steroids, alkaloids, benzopyran derivatives, and benzoic acid derivatives, amongst others. In this work, we review evidence that fungal extracts from multiple species can have beneficial effects on the lifespan and healthspan of model organisms, such as C. elegans worms, D. melanogaster flies, and M. musculus mice. We cover extraction methods and lifespan effects of Ganoderma lucidum (i.e. Reishi), Lentinula edodes (i.e. Shiitake), the genus Auricularia (i.e. jelly ear mushrooms), the genera Cordyceps and Ophiocordyceps (e.g. the caterpillar fungi), Hericium erinaceus (i.e. Lion's mane), the mold genus Monascus, and also Inonotus obliquus (i.e. Chaga), Grifola frondosa (i.e. Maitake or hen-of-the-woods), the genus Pleurotus (e.g. oyster mushrooms), and Agaricus subrufescens (i.e. the almond mushroom). We propose that further research on fungal extracts will provide a greater picture of the role fungi-derived bioactive molecules can have in developing longevity and neuroprotective medicines for humans.
Four new natural compounds named hericenone O (1), hericenone P (2), hericenone Q (3), and hericenone R (4), two of them were reported synthetically (3-4), together with eleven known compounds were isolated from the fruiting bodies of Hericium erinaceus. The chemical structures of the isolated compounds were elucidated by using NMR analysis and mass spectrometry, as well as comparisons with the reported data in the literature. The bioactivity evaluation revealed that hericenone Q showed significant cytotoxic activity against Hep-G2 with IC50 values of 23.89 μM, and against HCT-116 with IC50 values of 65.64 μM.
This Short Review covers the total synthesis of tetraketide-based meroterpenoids, i.e. geranyl-resorcinols, isolated from the mushrooms of genus Hericium. Some of these compounds are believed to be involved in the unique health-promoting effects of Hericium erinaceus. Herein, more than seventy natural products identified so far have been classified into seven-types based on both assumed biosynthetic pathways and chemical structures, and the successful total syntheses are summarized according to the structural type.
1 Introduction
2 Pioneering Synthetic Study
3 Total Synthesis of Geranyl-Resorcinol with a Geranyl Side Chain (Types 1, 3, and 6)
4 Total Synthesis of Geranyl-Resorcinol with an Oxidized Geranyl-Derived Side Chain (Types 2, 4, and 7)
5 Conclusion
Background
It is essential to detect morphological changes in the brain prior to the onset of cognitive decline. Although hippocampal volumes have been reported to be correlated with scores on neuropsychological tests, this relationship is still unclear among Japanese, non-demented older adults. Thus, this exploratory retrospective study aimed to identify neuropsychological tests that correlate with the degree of hippocampal atrophy in Japanese non-demented older adults.
Methods
Thirteen non-demented Japanese older adults aged 71.2±5.2 years were included. Hippocampal atrophy was evaluated by assessing the participants’ MRI scans using the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) software. Spearman’s partial correlation analyses were conducted to reveal relationships between VSRAD scores and neuropsychological test scores, including Raven’s Colored Progressive Matrices test (RCPM), the Standard Verbal Paired Associates Learning test (SP-A), and the Trail Making Test (TMT) scores by controlling for age, sex, and years of education.
Results
The Spearman’s partial correlation analysis results revealed that there were significant correlations between the degree of hippocampal atrophy and RCPM (Rho = -0.691, P = 0.027), TMT part B (Rho = 0.823, P = 0.003), and the related SP-A test scores (Rho = -0.691, P = 0.027).
Conclusions
Our results indicate that neuropsychological tests, particularly the TMT part B, might be used in assessing the degree of hippocampal atrophy in non-demented Japanese elderly individuals and should be studied further in the future to develop screening methods to detect brain atrophy.
In this study, 2-chloro-1,3-dimethoxy-5-methylbenzene (CDM), a natural product with anti-Candida albicans activity, was discovered from the Hericium erinaceus mycelium. The minimum inhibitory concentration of CDM was 62.5 μg/mL. Moreover, structural analogues of CDM obtained from chemical synthesis were applied to explore the structure-activity relationship (SAR) of CDM against C. albicans. It was found that methoxy groups, halogen atoms (except fluorine atoms), and methoxy-meta-position methyl groups in the structure of CDM were the key active groups. Furthermore, we investigated the anti-C. albicans mechanism of CDM. Experiments suggested that CDM destroyed the cell membrane of C. albicans, including the cytoplasmic membrane and mitochondrial membrane, and caused the accumulation of reactive oxygen species and mitochondrial dysfunction, which ultimately led to apoptosis of C. albicans. In addition, CDM had no toxicity on human normal gastric mucosal epithelial cells exposed to a concentration of 125 μg/mL. Experiments showed that CDM reduced the damage of C. albicans to the visceral tissue of infected mice and improved the survival rate of mice. Our research provides a scientific basis for the discovery of effective and safe anti-C. albicans drugs from H. erinaceus.
The presence of a fused 5/6/7 tricyclic core characterizes the group of cyathane diterpene natural products, that include more than 170 compounds, isolated from fungi such as Cyathus africanus and Hericium erinaceus. These compounds have a common biosynthetic precursor (cyatha-3,12-diene) and can be produced bio- or hemi-synthetically, or via total syntheses. Cyathane diterpenes display a range of pharmacological properties, including anti-inflammatory (possibly through binding to the iNOS protein) and neuroprotective effects. Many cyathanes like cyahookerin C, cyathin Q and cyafranines B and G can stimulate neurite outgrowth in cells, whereas conversely a few molecules (such as scabronine M) inhibit NGF-stimulated neurite outgrowth. The main anticancer cyathanes are erinacine A and cyathins Q and R, with a capacity to trigger cancer cell death dependent on the production of reactive oxygen species (ROS). These compounds, active both in vitro and in vivo, activate different signaling pathways in tumor cells to induce apoptosis (and autophagy) and to upregulate the expression of several proteins implicated in the organization and functioning of the actin cytoskeleton. An analysis of the functional analogy between erinacine A and other natural products known to interfere with the actin network in a ROS-dependent manner (notably cucurbitacin B) further supports the idea that erinacine A functions as a perturbator of the cytoskeleton organization. Collectively, we provide an overview of the molecular diversity of cyathane diterpenes and the main mechanisms of action of the lead compounds, with the objective to encourage further research with these fungal products. The anticancer potential of erinacine A deserves further attention but it will be necessary to better characterize the implicated targets and signaling pathways.
Hericium erinaceus , an ideal culinary-medicinal mushroom, has become a well-established candidate in promoting positive brain and nerve health-related activities by inducing the nerve growth factor from its bioactive ingredient. Among its active compounds, only erinacine A has confirmed pharmacological actions in the central nervous system in rats. Hence, this review has summarized the available information on the neurohealth properties of H. erinaceus mycelia enriched with erinacines, which may contribute to further research on the therapeutic roles of these mycelia. The safety of this mushroom has also been discussed. Although it has been difficult to extrapolate the in vivo studies to clinical situations, preclinical studies have shown that there can be improvements in ischemic stroke, Parkinson’s disease, Alzheimer’s disease, and depression if H. erinaceus mycelia enriched with erinacines are included in daily meals.
New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.
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.
Hericium erinaceus (H. erinaceus) has a long history of usage in traditional Chinese medicine for the treatment of gastric disorders. Recently, it has become a well-established candidate in causing positive brain and nerve health-related activities by inducing nerve growth factor (NGF) from its bioactive ingredient, erinacine A. This active compound, which exists only in fermented mycelium but not in its fruiting body, increases NGF levels in astroglial cells in vitro as well as catecholamine and NGF levels in vivo. With increasing recognition of erinacine A in H. erinaceus (EAHE) mycelium improving neurodegenerative diseases, numerous products are being marketed based on these functional claims. To our knowledge, there have been no reports on the mutagenicity of EAHE prior to this paper. Hence, the present study was undertaken to determine the mutagenicity and genotoxicity effects of EAHE mycelium conducted in three standard battery of tests (reverse mutation, chromosomal aberration, and micronuclei tests) according to the latest guidelines in order to meet all international regulatory requirements and provide information on the safety of this new and promising natural remedy. Our results have indicated that EAHE mycelium did not significantly increase the number of revertant colonies in the bacterial reverse mutation test nor induce higher frequency of aberrations in the chromosome aberration test. Moreover, no statistically significant EAHE mycelium-related increase was observed in the incidence of reticulocytes per 1000 red blood cells and micronucleated reticulocytes per 1000 reticulocytes. In conclusion, the three standard battery of tests suggested that EAHE mycelium was devoid of mutagenicity and genotoxicity in the tested doses and experimental conditions.
This review surveys the chemical and biological literature dealing with the isolation, structural elucidation and bioactivity of hericenones and erinacines from the fruiting body and mycelium of Hericium erinaceus, concentrating on work that has appeared in the literature up to December 2009.
Context
Nerve growth factor is a neurotrophic factor that promotes the survival
of small fiber sensory neurons and sympathetic neurons in the peripheral nervous
system. Recombinant human nerve growth factor (rhNGF) has demonstrated efficacy
as treatment for peripheral neuropathy in experimental models and phase 2
clinical trials.Objective
To evaluate the efficacy and safety of a 12-month regimen of rhNGF in
patients with diabetic polyneuropathy.Design
Randomized, double-blind, placebo-controlled phase 3 trial conducted
from July 1997 through May 1999.Setting
Eighty-four outpatient centers throughout the United States.Patients
A total of 1019 men and women aged 18 to 74 years with either type 1
or type 2 diabetes and a sensory polyneuropathy attributable to diabetes.Interventions
Patients were randomly assigned to receive either rhNGF, 0.1 µg/kg
(n = 504), or placebo (n = 515) by subcutaneous injection 3 times per week
for 48 weeks. Patients were assessed at baseline, 12 weeks, 24 weeks, and
48 weeks.Main Outcome Measures
The primary outcome measure was a change in neuropathy between baseline
and week 48, demonstrated by the Neuropathy Impairment Score for the Lower
Limbs, compared between the 2 groups. Secondary outcome measures included
quantitative sensory tests using the CASE IV System, the Neuropathy Symptom
and Change questionnaire, the Patient Benefit Questionnaire (PBQ), and a global
symptom assessment, as well as nerve conduction studies and occurrence of
new plantar foot ulcers. Patients also were evaluated for presence of adverse
events.Results
Among patients who received rhNGF, 418 (83%) completed the regimen compared
with 461 (90%) who received placebo. Administration of rhNGF was safe, with
few adverse events attributed to treatment apart from injection site pain/hyperalgesia
and other pain syndromes. However, neither the primary end point (P = .25) nor most of the secondary end points demonstrated a significant
benefit of rhNGF. Exceptions were the global symptom assessment (P = .03) and 2 of 32 comparisons within the PBQ, which showed a modest
but significant benefit of rhNGF (P = .05 for severity
of pain in the legs and P = .003 for 6-month symptoms
in the feet and legs).Conclusion
Unlike previous phase 2 trials, this phase 3 clinical trial failed to
demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy.
Figures in this Article
Nerve growth factor (NGF) is a protein that plays a major role in the
development and maintenance of the peripheral nervous system. Nerve growth
factor selectively promotes the survival of small fiber sensory neurons that
mediate pain, temperature sensation, and sympathetic neurons.1
Nerve growth factor is expressed in target tissues innervated by responsive
neurons, where it binds to specific high-affinity receptors and is retrogradely
transported back to the neuronal cell body.2
Recent data suggest that reduced availability of NGF may play a significant
role in the pathogenesis of diabetic polyneuropathy. In animals with diabetes
mellitus, retrograde axonal transport of NGF is impaired,3- 5
and levels of NGF messenger RNA are reduced in neuronal target tissues.6 In patients with diabetes mellitus, levels of NGF
are reduced in skin biopsy specimens. Furthermore, the diminished levels of
NGF in the skin correlate with decreased skin axon-reflex vasodilatation,
suggesting that reduced availability of NGF from the target tissue leads to
early dysfunction of small fiber neurons.7
Systemic administration of NGF prevents manifestations of neuropathy in rodent
models of toxic8- 9 and diabetic
polyneuropathy.10 That loss of NGF might contribute
toward the pathogenesis of diabetic polyneuropathy plus the demonstrated ability
of exogenous NGF to prevent experimental neuropathy provided a compelling
rationale for testing NGF administration in clinical studies.
Two randomized, placebo-controlled trials of recombinant human NGF (rhNGF)
administered to patients with polyneuropathy were initiated. In a phase 2
trial of 250 patients with diabetic polyneuropathy, improvements in signs
and symptoms were seen after treatment with rhNGF, 0.1 or 0.3 µg/kg,
subcutaneously, 3 times per week for 6 months.11
A second phase 2 trial of 270 patients with human immunodeficiency virus (HIV)–associated
sensory neuropathy demonstrated significant improvements in neuropathic pain
following 18 weeks of treatment with rhNGF, 0.1 or 0.3 µg/kg, twice
a week.12 Recombinant human NGF was well tolerated
with the exception of self-limited injection site hyperalgesia and other pain-related
syndromes. This article reports the results of a large randomized, double-blind,
placebo-controlled, phase 3 study of rhNGF administered to patients with diabetic
polyneuropathy to determine safety and efficacy during a 12-month period.
The physiological role of the neurotrophin nerve growth factor (NGF) has been characterized, since its discovery in the 1950s, first in the sensory and autonomic nervous system, then in central nervous, endocrine and immune systems. NGF plays its trophic role both during development and in adulthood, ensuring the maintenance of phenotypic and functional characteristic of several populations of neurons as well as immune cells. From a translational standpoint, the action of NGF on cholinergic neurons of the basal forebrain and on sensory neurons in dorsal root ganglia first gained researcher's attention, in view of possible clinical use in Alzheimer's disease patients and in peripheral neuropathies respectively. The translational and clinical research on NGF have, since then, enlarged the spectrum of diseases that could benefit from NGF treatment, at the same time highlighting possible limitations in the use of the neurotrophin as a drug. In this review we give a comprehensive account for almost all of the clinical trials attempted until now by using NGF. A perspective on future development for translational research on NGF is also discussed, in view of recent proposals for innovative delivery strategies and/or for additional pathologies to be treated, such as ocular and skin diseases, gliomas, traumatic brain injuries, vascular and immune diseases.
Many older individuals experience cognitive decline with aging. The causes of cognitive dysfunction range from the devastating effects of Alzheimer's disease (AD) to treatable causes of dysfunction and the normal mild forgetfulness described by many older individuals. Even mild cognitive dysfunction can impact medication adherence, impair decision making, and affect the ability to drive or work. However, primary care physicians do not routinely screen for cognitive difficulties and many older patients do not report cognitive problems. Identifying cognitive impairment at an office visit would permit earlier referral for diagnostic work-up and treatment. The Computer Assessment of Mild Cognitive Impairment (CAMCI) is a self-administered, user-friendly computer test that scores automatically and can be completed independently in a quiet space, such as a doctor's examination room. The goal of this study was to compare the sensitivity and specificity of the CAMCI and the Mini Mental State Examination (MMSE) to identify mild cognitive impairment (MCI) in 524 nondemented individuals > 60 years old who completed a comprehensive neuropsychological and clinical assessment together with the CAMCI and MMSE. We hypothesized that the CAMCI would exhibit good sensitivity and specificity and would be superior compared with the MMSE in these measures. The results indicated that the MMSE was relatively insensitive to MCI. In contrast, the CAMCI was highly sensitive (86%) and specific (94%) for the identification of MCI in a population of community-dwelling nondemented elderly individuals.
Several findings obtained in recent years suggest that NGF, aside from its well-established function as a neurotrophic factor for peripheral sympathetic and sensory neurons, also has trophic influence on the cholinergic neurons of the basal forebrain. The present study assessed whether NGF was able to affect survival of central cholinergic neurons after axonal transections in adult rats. The septo-hippocampal pathway was transected unilaterally by cutting the fimbria, and animals were implanted with a cannula through which NGF or control solutions were injected intraventricularly over 4 weeks. The lesions reduced the number of large cell bodies, as visualized by Nissl staining in the medial septal nucleus and in the vertical limb of the diagonal band of Broca. Furthermore, in the same nuclei, they reduced the number of cell bodies positively stained for AChE after pretreatment with diisopropylfluorophosphate (a method known to result in reliable identification of cholinergic neurons in the septal area). On lesioned sides, the number of cholinergic cells in medial septal nucleus and the vertical limb of the diagonal band was reduced by 50 +/- 4%, as compared to the number on contralateral sides. On lesioned sides of animals chronically treated with NGF, the number of AChE-positive cells in these areas was reduced only by 12 +/- 6%, as compared to control levels. These findings suggest that fimbrial transections resulted in retrograde degeneration of cholinergic septo-hippocampal neurons and that NGF treatment strongly attenuated this lesion-induced degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)
β-Glucans are a class of polysaccharides consisting of D-glucose units that are polymerized primarily via the β-1,3 glycosidic bonds, in addition to the β-1,4 and/or β-1,6 bonds. They are present in various food products such as cereals, mushrooms, and seaweeds and are known for their numerous effects on the human body, depending on their structures, which are diverse. The major physicochemical properties of β-glucans include their antioxidant property, which is responsible for the scavenging of reactive oxygen species, and their role as dietary fiber for preventing the absorption of cholesterol, for promoting egestion, and for producing short-chain fatty acids in the intestine. Dietary β-glucans also exert immunostimulatory and antitumor effects by activation of cells of the mucosal immune system via β-glucan receptors, such as dectin-1. In this review, we elaborate upon the diversity of the structures and functions of β-glucans present in food, along with discussing their proposed mechanisms of action. In addition to the traditional β-glucan-containing foods, recent progress in the commercial mass cultivation and supply of an algal species, Euglena gracilis, as a food material is briefly described. Mass production has enabled consumption of paramylon, a Euglena-specific novel β-glucan source. The biological effects of paramylon are discussed and compared with those of other β-glucans.
Neurons extend neurites with an increased synthesis of phosphatidylcholine (PC) that is not only a membrane component but also a functional regulator with specific fatty acid composition. To analyze the local synthesis of the PC molecular species within neurons, we combined a compartmentalized culture system with matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). We observed that a newly synthesized PC, which contains exogenously administered palmitic acid-d3, is accumulated at the cell bodies and the tips of the distal neurites. The local accumulation within distal neurites is formed by distinct metabolic activity from cell bodies, suggesting that the local extracellular composition of free fatty acid can be a key to regulate specific functions of each PC molecular species. We expect our simple method to be a starting point for more sophisticated in vitro analytical methods for unveiling detailed lipid metabolisms within neurons.
Hericium erinaceus (H. erinaceus) improves the symptoms of menopause. In this study, using ovariectomized mice as a model of menopause, we investigated the anti-obesity effect of this mushroom in menopause. Mice fed diets containing H. erinaceus powder showed significant decreases in the amounts of fat tissue, plasma levels of total cholesterol, and leptin. To determine the mechanism, groups of mice were respectively fed a diet containing H. erinaceus powder, a diet containing ethanol extract of H. erinaceus, and a diet containing a residue of the extract. As a result, H. erinaceus powder was found to increase fecal lipid levels in excreted matter. Further in vitro investigation showed that ethanol extract inhibited the activity of lipase, and four lipase-inhibitory compounds were isolated from the extract: hericenone C, hericenone D, hericenone F, and hericenone G. In short, we suggest that H. erinaceus has an anti-obesity effect during menopause because it decreases the ability to absorb lipids.
Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.
Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies.
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.
Total syntheses of 5'- and 7'-oxidized geranyl resorcylates isolated from the fruiting bodies of Hericium erinaceum and the submerged cultures of a Stereum species were achieved. Our synthesis features derivatization of a suitably functionalized 5'-oxidized geranyl phthalide as a common intermediate, which was obtained by Stille coupling between the phthalide core and the side chain, into a series of natural products by divergent functional group manipulations. The crucial C5'-oxygen functionality was installed at the initial stage by alkylation by an alpha-cyano ethoxyethyl ether. From a common synthetic intermediate, eight total syntheses including hericenones A, B, and I, hericenols B, C and D, and erinacerins A and B were achieved (hericenol B and erinacerin B were synthesized as racemates). The structure of hericenone B established in the isolation paper was unambiguously revised as the carbonyl regioisomer at the lactam moiety.
Novel cytotoxic phenols, hericenone A () and B () were isolated from the mushroom . These structures were determined by interpretation of spectral data and chemical analyses.
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.
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).
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.
Nerve growth factor (NGF) is an essential protein for supporting growth and maintenance of peripheral sympathetic neurons. A novel diterpenoid erinacine, isolated from the cultured mycelia of Hericium erinacium, is known to have a potent stimulating effect on NGF synthesis. The effects of erinacine and related compounds in the brain in vivo are not known. In this study, we examined the effects of erinacine A on the production of NGF and catecholamines which stimulate NGF synthesis in the brain of rats. Rats were treated with erinacine A by intubation for the first 3 weeks from birth to weaning and intragastrically from weeks 4 to 5. Rats treated with this compound had increased levels of both noradrenaline and homovanillic acid in the locus coeruleus (LC) at 4 weeks of age and increased levels of NGF in both LC and hippocampus at 5 weeks of age. The effects of erinacine A were confirmed in the central nervous system in rats.
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.
Neonatal rats received intraventricular injections of mouse submandibular gland nerve growth factor (NGF) on days 1, 3, 5 and 7 postpartum. After killing the animals at day 8, activities of choline acetyltransferase (ChAT), acetylcholine esterase (AChE) and tyrosine hydroxylase (TH) were measured in different brain areas. NGF treatment increased ChAT activity in the septal area by 78%, in the hippocampus by 30%, and in the cortex by 73% relative to control animals. No increase was observed in other brain areas. The elevation of ChAT activity was not accompanied by an increased activity of AChE, and the concomitant 30–40% increase of TH activity observed in the cortex and brainstem was abolished after immunosympathectomy, reflecting the ingrowth of peripheral sympathetic peripheral fibers into the central nervous system (CNS) in response to centrally administered NGF²³. In adult rats, repeated injections of NGF over 4 weeks caused a small but statistically significant increase of ChAT activity (15%) in the forebrain.
We investigated antitumor effects of the following four extracts of freeze-dried Hericium erinaceus mushrooms in Balb/c mice intracutaneously transplanted on the backs with CT-26 colon cancer cells: HWE, hot water extraction by boiling in water for 3 h; MWE, microwaving in 50% ethanol/water at 60 W for 3 min; and ACE and AKE, boiling in 1% HCl or 3% NaOH for 2 h. HWE and MWE with a higher content of β-glucans, determined by an assay kit, than ACE and MKE were active in all bioassays. Gas chromatography/mass spectrometry analyses showed the presence of 40, 27, 16, and 13 compounds, respectively, in the four extracts. Daily intraperitoneal (ip) injections of HWE and MWE for 2 weeks significantly reduced tumor weights by 38 and 41%. Tumor regressions were associated with changes in the following cancer biomarkers as compared to phosphate buffer (PBS)-treated control mice: 2.7- and 2.4-fold increases in cytolytic activity of splenic natural killer (NK) cells; restored nitric oxide production and phagocytosis in peritoneal macrophages to 95-98% of normal levels; ∼2-fold increase in released pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 from macrophages; and ∼56 and ∼60% reductions in the number of blood vessels inside the tumor. The pro-angiogenic factors vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and 5-lipoxygenase (5-LOX) were also significantly reduced in mRNA and protein expression by tumor genes. Enzyme-linked immunosorbent assay of tumor cells confirmed reduced expression of COX-2 and 5-LOX (32 and 31%). Reduced COX-2 and 5-LOX expression down-regulated VEGF expression, resulting in inhibition of neo-angiogenesis inside the tumors. The results indicate that induction of NK activity, activation of macrophages, and inhibition of angiogenesis all contribute to the mechanism of reduction of tumor size.
The visual retention test to be described here was developed as a practical means of fulfilling what I have long felt to be a need in the usual clinical examination of patients, namely, a short test to supplement the auditory-vocal digit span test in the investigation of immediate memory.The auditory-vocal digit span test, devised in 1887 by Jacobs,1 has become a stable feature of most clinical examination schemes. It measures retention or immediate memory, which is justifiably considered to be a significant aspect of mental capacity and one which is especially important clinically because of its close relationship to mental impairment. The test has obvious technical advantages, such as brevity of administration, lack of need for test materials and the objective character of the patient's performance.Nevertheless, while it is a useful single test, both clinical experience and experimental observations indicate that it cannot be considered to be
Hericium erinaceus, a well known edible mushroom, has numerous biological activities. Especially hericenones and erinacines isolated from its fruiting body stimulate nerve growth factor (NGF) synthesis, which expects H. erinaceus to have some effects on brain functions and autonomic nervous system. Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, "insentive" and "palpitatio", each of the mean score of the HE group was significantly lower than the placebo group. "Concentration", "irritating" and "anxious" tended to be lower than the placebo group. Our results show that HE intake has the possibility to reduce depression and anxiety and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus.
Platelet aggregation in the blood vessel causes thrombosis. Therefore, inhibitors of platelet aggregation promise to be preventive or therapeutic agents of various vascular diseases, including myocardial infarction and stroke. In the present study, we found that hericenone B had a strong anti-platelet activity and it might be a novel compound for antithrombotic therapy possessing a novel mechanism. Prior to this study, we examined anti-platelet aggregation activity of ethanol extracts of several species of mushrooms, and found that extract of Hericium erinaceus potently inhibited platelet aggregation induced by collagen. Therefore, we first fractionated the ethanol extract of H. erinaceus to identify the active substances. The anti-platelet activity of each fraction was determined using washed rabbit platelets. As a result, an active component was isolated and identified as hericenone B. Hericenone B selectively inhibited collagen-induced platelet aggregation, but it did not suppress the aggregation induced by U46619 (TXA₂ analogue), ADP, thrombin, or adrenaline. Furthermore, hericenone B did not inhibit arachidonic acid- or convulxin (GPVI agonist)-induced platelet aggregation. Therefore, hericenone B was considered to block collagen signaling from integrin α2/β1 to arachidonic acid release. Moreover, we found that collagen-induced aggregation was inhibited by hericenone B in human platelets, similar to in rabbit platelets.
Compare diagnostic characteristics of brief cognitive screening tests in residential care/assisted living (RC/AL) residents.
Cross-sectional study involving a comprehensive clinical examination to ascertain a consensus diagnosis of probable dementia, no significant cognitive impairment, or mild cognitive impairment (MCI), including both amnestic and non-amnestic subtypes.
Fourteen RC/AL facilities in North Carolina.
Participants were 146 RC/AL residents, aged 65 years or older, who did not have diagnosed cognitive impairment.
Diagnostic characteristics of the Mini-Cog, the Mini-Mental State Exam (MMSE), and a new 50-point test based on expanding selected MMSE items (MMX).
Overall, 55/146 (38%) participants were diagnosed with probable dementia, and 76 (52%) met criteria for MCI (most non-amnestic). Both the Mini-Cog and the MMSE showed high sensitivity and negative predictive value for dementia, but had relatively low sensitivity and negative predictive value for MCI. The Mini-Cog had low specificity and was less accurate as a dementia screen than either the MMSE or MMX. Reliability and validity data for the MMX were satisfactory, and it performed better as a screening test for MCI than either the MMSE or Mini-Cog.
Although the MMSE and Mini-Cog are both sensitive to dementia, modest specificity and positive predictive value may limit their utility as screening tools. Preliminary MMX data suggest it improves screening for MCI compared to the Mini-Cog or MMSE, while providing a similar level of screening for dementia. Further work is needed to identify suitable instruments for cognitive screening across the range of MCI and dementia.
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.
A cut or crush injury to a peripheral nerve results in the degeneration of that portion of the axon isolated from the cell body. The rapid degeneration of this distal segment was for many years believed to be a process intrinsic to the nerve. It was believed that Schwann cells both phagocytosed degenerating axons and myelin sheaths and also provided growth factors to promote regeneration of the damaged axons. In recent years, it has become apparent that the degenerating distal segment is invaded by monocytes from the blood. We will review the evidence that these recruited macrophages play a role in both degeneration and regeneration of peripheral nerve axons after injury and consider whether the slow degeneration and poor monocyte recruitment in the central nervous system may contribute to the poor regeneration there.
Macrophages are not only phagocytic cells but also secrete a plethora of growth factors that are potentially important for regeneration. This review will examine the emerging evidence of a likely contribution by macrophages to axonal regeneration.
This review summarizes the current knowledge of characterized neurotrophic factors, including nerve growth factor (NGF) which serves as paradigmatic example when studying novel molecules. Special consideration is given to the function of neurotrophic factors in the adult and aging brain. Strategies are discussed for the eventual development of pharmacological applications of these molecules in the treatment of neurodegenerative diseases.
Preclinical studies have demonstrated that nerve growth factor may prevent or reverse peripheral neuropathy. We have therefore tested the effects of recombinant human nerve growth factor in patients with diabetic polyneuropathy.
A total of 250 patients with symptomatic diabetic polyneuropathy randomly received either placebo or one of two doses of recombinant human nerve growth factor for 6 months. Patients were assessed for symptoms and signs of polyneuropathy before and after treatment.
Compared with placebo, recombinant human nerve growth factor led to significant improvement after 6 months of treatment, as measured by the sensory component of the neurologic examination, two quantitative sensory tests, and the impression of most subjects that their neuropathy had improved. Three prospectively identified multiple endpoint analyses indicated improvements in the nerve growth factor treatment groups over the placebo group in all three analyses (p = 0.032; p = 0.008; p = 0.005). Recombinant human nerve growth factor was well tolerated, with injection site discomfort reported as the most frequent adverse event.
Recombinant human nerve growth factor appears to be safe and shows preliminary evidence of efficacy in patients with symptomatic diabetic polyneuropathy.
Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system. Recombinant human nerve growth factor (rhNGF) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials.
To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy.
Randomized, double-blind, placebo-controlled phase 3 trial conducted from July 1997 through May 1999.
Eighty-four outpatient centers throughout the United States.
A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes.
Patients were randomly assigned to receive either rhNGF, 0.1 microg/kg (n = 504), or placebo (n = 515) by subcutaneous injection 3 times per week for 48 weeks. Patients were assessed at baseline, 12 weeks, 24 weeks, and 48 weeks.
The primary outcome measure was a change in neuropathy between baseline and week 48, demonstrated by the Neuropathy Impairment Score for the Lower Limbs, compared between the 2 groups. Secondary outcome measures included quantitative sensory tests using the CASE IV System, the Neuropathy Symptom and Change questionnaire, the Patient Benefit Questionnaire (PBQ), and a global symptom assessment, as well as nerve conduction studies and occurrence of new plantar foot ulcers. Patients also were evaluated for presence of adverse events.
Among patients who received rhNGF, 418 (83%) completed the regimen compared with 461 (90%) who received placebo. Administration of rhNGF was safe, with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes. However, neither the primary end point (P =.25) nor most of the secondary end points demonstrated a significant benefit of rhNGF. Exceptions were the global symptom assessment (P =.03) and 2 of 32 comparisons within the PBQ, which showed a modest but significant benefit of rhNGF (P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs).
Unlike previous phase 2 trials, this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy. JAMA. 2000;284:2215-2221.
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.
Since their discovery in the 1950s, neurotrophic factors have raised expectations that their clinical application to neurodegenerative diseases might provide an effective therapy for what are now untreatable conditions. Nerve growth factor (NGF) was the first neurotrophic factor to be discovered and was one of the earliest to proceed to clinical trials. NGF, which is selectively trophic for small fiber sensory and sympathetic neurons, was selected as a potential theraphy for diabetic polyneuropathy becaus of the serious consequences associated with degeneration of those neuronal populations in this condition. In addition, evidence shows that reduced availability of NGF may contribute to the pathogenesis of diabetic neuropathy, and animal models of neuropathy respond to the exogenous administration of NGF. Two sets of phase II clinical trails suggested that recombinant human NGF (rhNGF) administration was effective at ameliorating the symptoms associated with both diabetic polyneuropathy and HIV-related neuropathy. These early studies, however, revealed that painful side effects were dose limiting for NGF. A large-scale phase III clinical trail of 1019 patients randomized to receive either rhNGF or palcebo for 48 weeks failed to confirm the earlier indications of efficacy. Among the explanations offered for the discrepancy between the two sets of trails was a robust palcebo effect, inadequate dosage, different study populatioms, and changes to the formulation of rhNGF for the phase III trail. As a result of the phase III outcome, Genentech has decided not to proceed with further development of rhNGF.
HEP3, a beta-D-glucan slightly soluble in water, was isolated from the alkaline extract of the fruiting bodies of Hericium erinaceus. Its chemical structure was investigated by methylation analysis, periodate oxidation, Smith degradation and by IR and NMR spectroscopy. It was shown to have a main chain composed of beta-(1-->3)-linked D-glucopyranosyl residues, with single unit glucosyl branches attached to O-6 of every third backbone residue. Viscometry and Congo red reaction indicated that HEP3 has a highly ordered hydrogen-bond dependent conformation in aqueous solution, which collapses in strong alkaline solution.
The Mini-Mental State Examination (MMSE) is commonly used as a screening tool to detect dementia. However, it performs poorly in identifying persons with mild neurocognitive disorder. The Saint Louis University Mental Status (SLUMS) examination is a 30-point screening questionnaire that tests for orientation, memory, attention, and executive functions.
The objective of this study was to compare SLUMS and the MMSE for detecting dementia and mild neurocognitive disorder (MNCD) using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
Patients at the Veterans' Affairs Geriatric Research, Education and Clinical Center, St. Louis, MO (N = 702) were clinically classified as having normal cognitive functioning, MNCD, or dementia based on DSM-IV criteria. The SLUMS and MMSE were administered for comparison.
Mean age was 75.3 years (standard deviation: 5.5). Regarding education, 62.4% of the sample had at least completed high school and 30.6% had not. Sensitivity and specificity were calculated and receiver operator curves (ROCs) generated for SLUMS and MMSE as a function of diagnosis (MCND versus dementia) and education. Both the SLUMS and MMSE produced acceptable ROCs for the diagnosis of dementia, but the ROCs for SLUMS were better than the MMSE for the diagnosis of MNCD in both education groups.
These results suggest that the SLUMS and MMSE have comparable sensitivities, specificities, and area under the curve in detecting dementia. Although the definition of MNCD is controversial, the authors believe that the SLUMS is possibly better at detecting mild neurocognitive disorder, which the MMSE failed to detect, but this needs to be further investigated.
Little is known about how synaptic activity is modulated in the central nervous system. We have identified SCRAPPER, a synapse-localized E3 ubiquitin ligase, which regulates neural transmission. SCRAPPER directly binds and ubiquitinates RIM1, a modulator of presynaptic plasticity. In neurons from Scrapper-knockout (SCR-KO) mice, RIM1 had a longer half-life with significant reduction in ubiquitination, indicating that SCRAPPER is the predominant ubiquitin ligase that mediates RIM1 degradation. As anticipated in a RIM1 degradation defect mutant, SCR-KO mice displayed altered electrophysiological synaptic activity, i.e., increased frequency of miniature excitatory postsynaptic currents. This phenotype of SCR-KO mice was phenocopied by RIM1 overexpression and could be rescued by re-expression of SCRAPPER or knockdown of RIM1. The acute effects of proteasome inhibitors, such as upregulation of RIM1 and the release probability, were blocked by the impairment of SCRAPPER. Thus, SCRAPPER has an essential function in regulating proteasome-mediated degradation of RIM1 required for synaptic tuning.
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A beta-D-glucan isolated from the fruiting bodies of Hericium erinaceus and its aqueous conformation
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