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Compounds for dementia from Hericium erinaceum

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Abstract

Our group has been conducting a search for compounds for dementia derived from medicinal mushrooms since 1991. A series of benzyl alcohol derivatives (named hericenones C to H), as well as a series of diterpenoid derivatives (named erinacines A to I) were isolated from the mushroom Hericium erinaceum. These compounds significantly induced the synthesis of nerve growth factor (NGF) in vitro and in vivo. In a recent study, dilinoleoyl-phosphatidylethanolamine (DLPE) was isolated from the mushroom and was found to protect against neuronal cell death caused by β-amyloid peptide (Aβ) toxicity, endoplasmic reticulum (ER) stress and oxidative stress. Furthermore, the results of preliminary clinical trials showed that the mushroom was effective in patients with dementia in improving the Functional Independence Measure (FIM) score or retarding disease progression. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

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... Existing data have suggested that there is a neuroprotective effect of dietary supplementation with H. erinaceus in mice subjected to middle cerebral artery occlusion [23]. Furthermore, H. erinaceus provided a partial recovery of intellectual function of patients with a mild cognitive impairment or against other forms of neurodegenerative diseases, including dementia and Alzheimer's [24,25,26]. It has been shown that erinacines A-I and hericenones C-H are responsible for the neuroprotective effects of stimulating Nerve Growth Factor (NGF) [27,28] and of brain derived neurotrophic factor (BDNF) synthesis in vitro [29,30]. ...
... It has been shown that erinacines A-I and hericenones C-H are responsible for the neuroprotective effects of stimulating Nerve Growth Factor (NGF) [27,28] and of brain derived neurotrophic factor (BDNF) synthesis in vitro [29,30]. A possible role of polysaccharides in neuroprotection has been suggested as well [25,27,31]. Additionally, the effects of H. erinaceus on recognition memory and on hippocampal mossy fiber-CA3 neurotransmission in wild-type middle-aged mice was recently published [32,33]. ...
... Furthermore, H. erinaceus is a seemingly good candidate to regress recognition memory decline during aging, possibly through an increase in neurogenesis in the hippocampus and cerebellum. These findings rise the possibility that H. erinaceus extracts could be a new therapeutic strategy for preventing or treating neurodegenerative diseases such as dementia and Alzheimer's, as suggested by other authors [24,25,26]. Future studies should investigate the mechanisms involved in this at a cellular level. ...
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Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, implicated in both poor quality of life and negative health outcomes. One central question surrounding frailty is whether phenotypic frailty is associated with the cognitive impairment during aging. Using spontaneous behavioral tests and by studying the dynamic change during aging, we demonstrated that the two form of vulnerability, locomotor and recognition memory decline, develop in parallel and therefore, integration of the motoric and cognitive evaluations are imperative. We developed an integrated frailty index based on both phenotypic and recognition memory performances. Hericium erinaceus (H. erinaceus) is a medicinal mushroom that improves recognition memory in mice. By using HPLC-UV-ESI/MS analyses we obtained standardized amounts of erinacine A and hericenones C and D in H. erinaceus extracts, that were tested in our animal model of physiological aging. Two-month oral supplementation with H. erinaceus reversed the age-decline of recognition memory. Proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) immunohistochemistry in the hippocampus and cerebellum in treated mice supported a positive effect of an H. erinaceus on neurogenesis in frail mice.
... Hericium erinaceus is an edible mushroom that belongs to the family Hericiaceae and has been used for the treatment of, e.g., digestive diseases in traditional Chinese medicine for more than 1000 years. Various compounds isolated from H. erinaceus, high molecular weight compounds as well as small molecules, have shown a variety of beneficial functions, such as anticancer, anti-inflammatory, and immunomodulatory properties [1][2][3][4][5]. Hericenones and erinacines are the major bioactive low molecular weight compounds formed by fruiting bodies and submerged cultures of H. erinaceus, respectively. ...
... Fungal Biology and Biotechnology *Correspondence: holger.zorn@uni-giessen.de 1 Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany Full list of author information is available at the end of the article shown to significantly induce nerve growth factor (NGF) synthesis and to protect neuronal cells against endoplasmic reticulum (ER) stress-or oxidative stress-induced cell death. Therefore, the consumption of H. erinaceus, and of dietary supplements derived thereof, has been suggested for the prevention and treatment of dementia, and especially of Alzheimer's disease [1,[6][7][8][9][10][11][12]. ...
... Fungal Biology and Biotechnology *Correspondence: holger.zorn@uni-giessen.de 1 Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany Full list of author information is available at the end of the article shown to significantly induce nerve growth factor (NGF) synthesis and to protect neuronal cells against endoplasmic reticulum (ER) stress-or oxidative stress-induced cell death. Therefore, the consumption of H. erinaceus, and of dietary supplements derived thereof, has been suggested for the prevention and treatment of dementia, and especially of Alzheimer's disease [1,[6][7][8][9][10][11][12]. ...
Article
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Fungi of the phylum Basidiomycota are well-known to form a broad spectrum of biologically active secondary metabolites, especially low molecular weight compounds such as terpenoids. Hericium erinaceus produces various cyathane type diterpenoids including erinacines. However, no quantitative data and production kinetics have been reported on the biosynthesis of the erinacines C and P in submerged cultures. In the present study, the production of erinacine C was optimized, and the product formation kinetics as well as the antimicrobial activity were studied by high-performance liquid chromatography (HPLC), high-performance thin-layer chromatography (HPTLC) and direct bioautography. Oatmeal and Edamin ® K were identified to be crucial media components for an efficient production of erinacine C. The highest concentrations of erinacine C were obtained in the optimized culture medium on the 9 th culture day (approximately 260 mg L −1 ). The production of erinacine P was strongly time dependent. The maximum concentration of erinacine P of 184 mg L −1 was observed on the third culture day. Afterwards, the concentrations of erinacine P decreased while the concentrations of erinacine C steadily increased. Comparable results were obtained by HPTLC with UV detection and HPLC with diode-array detection (DAD) analyses. Direct bioautography allowed for an additional analysis of the antimicrobial activity of the secondary metabolites. The C and N sources oatmeal and Edamin ® K induced the formation of erinacine C. Detailed product formation kinetics of the erinacines C and P have been reported for the first time. HPTLC combined with the Aliivibrio fischeri bioassay allowed for an instant detection of cyathane diterpenoids in crude extracts and for an evaluation of the antimicrobial activity of the secondary metabolites directly on the plate.
... Використання гериценона С та еринацина А рекомендують для покращення функцій пам'яті і поліпшення навчання. Доведено, що ці сполуки можуть суттєво впливати на синтез NGF in vitro та / або in vivo (Kawagishi & Zhuang 2008;Khan et al., 2013;Soares et al., 2013;Jiang et al., 2014;Thongbai et al., 2015;Zhang et al., 2015;Wong et al., 2016). ...
... Її тепер називають амілобаном (інша назва -аміценон). Як показали подальші дослідження, H. erinaceus містить як мінімум дві речовини -гериценони та амілобан, які є ефективними проти ушкодження мозку людини при хворобах Альцгеймера та Паркінсона (Kawagishi et al., 1990(Kawagishi et al., , 1993Kawagishi & Zhuang 2008). Описані фізіологічні та ноотропні дії аміценону (амілобан, що міститься в стандартизованому екстракті H. erinaceum), який є активатором функції головного мозку. ...
... Інша біологічно активна речовина, названа 3-гідроксигерицинон F, показала захисну дію проти загибелі клітин нейронів через ЕR стрес (Ueda et al., 2009). Крім того, показник функціональної незалежності щодо прогресування хвороби попередніх клінічних випробувань показали поліпшення стану у пацієнтів з деменцією (Kawagishi, Zhuang 2008). ...
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В огляді представлені результати сучасних досліджень та перспективи застосування грибів роду Hericium в профілактичних та лікувальних цілях. Найбільш відомим представником цієї родини є H. erinaceum — цінний їстівний лікарський гриб, який здавна використовували в народній медицині та традиційній кухні країн Східної Азії, насамперед, Китаю. Сучасні відомості щодо лікувальних властивостей H.erinaceus свідчать про широкий біологічний спектр його дії. Загалом з плодових тіл, міцелію та культуральної рідини H.erinaceus виділено близько 70 біоактивних сполук, перспективних для запобігання або лікування хронічних, когнітивних та неврологічних захворювань людини. Особливу увагу приділено грибним полісахаридам і вторинним метаболітам, таким як гериценони, еринацини, цереброзиди, аміценон тощо. Повідомляється про імуномодулюючу, протипухлинну, гастропротекторну, нейропротекторну, нейротрофічну, цитопротекторну, антиоксидантну, антибактеріальну, гіпоглікемічну, гепатопротекторну дію екстрактів H. erinaceum. Нечисленні повідомлення стосуються утворення метаболітів іншими представниками роду Hericium. Наведено дані щодо виділення еринацинів із H. flagellum та нової групи сполук — коралоцинів із H. coralloides, що індукують нейротрофічний ростовий фактор та нейротрофічний фактор головного мозку.
... Використання гериценона С та еринацина А рекомендують для покращення функцій пам'яті і поліпшення навчання. Доведено, що ці сполуки можуть суттєво впливати на синтез NGF in vitro та / або in vivo (Kawagishi & Zhuang 2008;Khan et al., 2013;Soares et al., 2013;Jiang et al., 2014;Thongbai et al., 2015;Zhang et al., 2015;. ...
... Її тепер називають амілобаном (інша назва -аміценон). Як показали подальші дослідження, H. erinaceus містить як мінімум дві речовини -гериценони та амілобан, які є ефективними проти ушкодження мозку людини при хворобах Альцгеймера та Паркінсона (Kawagishi et al., 1990(Kawagishi et al., , 1993Kawagishi & Zhuang 2008). Описані фізіологічні та ноотропні дії аміценону (амілобан, що міститься в стандартизованому екстракті H. erinaceum), який є активатором функції головного мозку. ...
... Інша біологічно активна 537 речовина, названа 3-гідроксигерицинон F, показала захисну дію проти загибелі клітин нейронів через ЕR стрес (Ueda et al., 2009). Крім того, показник функціональної незалежності щодо прогресування хвороби попередніх клінічних випробувань показали поліпшення стану у пацієнтів з деменцією (Kawagishi, Zhuang 2008). ...
Book
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The collection of papers is dedicated to the 95th anniversary of the famous Ukrainian biologist, director of the Central Republican Botanical Garden (now M.M. Grishko National Botanical Garden NAS of Ukraine), chairman of the Council of Botanical Gardens of Ukraine and Moldova, founder of modern allelopathy and theoretical foundations of phytodesign, Doctor of Biological Sciences, Professor, Academician of the Academy of Sciences of the Ukrainian SSR - Andriy Mykhailovich Grodzinsky (1926–1988). The book contains: memories of relatives and colleagues of the scientist, which reflect the main stages of life, scientific, organizational, social activities of A.M. Grodzinsky; publications devoted to some modern aspects of botany and mycology, which include allelopathy, ecology, taxonomy, physiology etc.
... Використання гериценона С та еринацина А рекомендують для покращення функцій пам'яті і поліпшення навчання. Доведено, що ці сполуки можуть суттєво впливати на синтез NGF in vitro та / або in vivo (Kawagishi & Zhuang 2008;Khan et al., 2013;Soares et al., 2013;Jiang et al., 2014;Thongbai et al., 2015;Zhang et al., 2015;. ...
... Її тепер називають амілобаном (інша назва -аміценон). Як показали подальші дослідження, H. erinaceus містить як мінімум дві речовини -гериценони та амілобан, які є ефективними проти ушкодження мозку людини при хворобах Альцгеймера та Паркінсона (Kawagishi et al., 1990(Kawagishi et al., , 1993Kawagishi & Zhuang 2008). Описані фізіологічні та ноотропні дії аміценону (амілобан, що міститься в стандартизованому екстракті H. erinaceum), який є активатором функції головного мозку. ...
... Інша біологічно активна 537 речовина, названа 3-гідроксигерицинон F, показала захисну дію проти загибелі клітин нейронів через ЕR стрес (Ueda et al., 2009). Крім того, показник функціональної незалежності щодо прогресування хвороби попередніх клінічних випробувань показали поліпшення стану у пацієнтів з деменцією (Kawagishi, Zhuang 2008). ...
Book
Full-text available
Збірка праць присвячена 95-річчю з дня народження відомого українського вченого-біолога, директора Центрального республіканського ботанічного саду (нині Національний ботанічний сад імені М. М. Гришка НАН України), голови Ради ботанічних садів України та Молдови, засновника сучасної алелопатії та теоретичних основ фітодизайну, доктора біологічних наук, професора, академіка АН УРСР – Андрія Михайловича Гродзинського (1926–1988). Видання містить: спогади рідних та колег вченого, які відображають основні етапи життя, наукову, організаційну, громадську діяльність А.М. Гродзинського; розділи, присвячені деяким сучасним аспектам ботаніки та мікології, які включають алелопатію, екологію, таксономію, фізіологію та ін.
... Використання гериценона С та еринацина А рекомендують для покращення функцій пам'яті і поліпшення навчання. Доведено, що ці сполуки можуть суттєво впливати на синтез NGF in vitro та / або in vivo (Kawagishi & Zhuang 2008;Khan et al., 2013;Soares et al., 2013;Jiang et al., 2014;Thongbai et al., 2015;Zhang et al., 2015;. ...
... Її тепер називають амілобаном (інша назва -аміценон). Як показали подальші дослідження, H. erinaceus містить як мінімум дві речовини -гериценони та амілобан, які є ефективними проти ушкодження мозку людини при хворобах Альцгеймера та Паркінсона (Kawagishi et al., 1990(Kawagishi et al., , 1993Kawagishi & Zhuang 2008). Описані фізіологічні та ноотропні дії аміценону (амілобан, що міститься в стандартизованому екстракті H. erinaceum), який є активатором функції головного мозку. ...
... Інша біологічно активна 537 речовина, названа 3-гідроксигерицинон F, показала захисну дію проти загибелі клітин нейронів через ЕR стрес (Ueda et al., 2009). Крім того, показник функціональної незалежності щодо прогресування хвороби попередніх клінічних випробувань показали поліпшення стану у пацієнтів з деменцією (Kawagishi, Zhuang 2008). ...
Book
The collection of papers is dedicated to the 95th anniversary of the famous Ukrainian biologist, director of the Central Republican Botanical Garden (now M.M. Grishko National Botanical Garden NAS of Ukraine), chairman of the Council of Botanical Gardens of Ukraine and Moldova, founder of modern allelopathy and theoretical foundations of phytodesign, Doctor of Biological Sciences, Professor, Academician of the Academy of Sciences of the Ukrainian SSR - Andriy Mykhailovich Grodzinsky (1926–1988). The book contains: memories of relatives and colleagues of the scientist, which reflect the main stages of life, scientific, organizational, social activities of A.M. Grodzinsky; publications devoted to some modern aspects of botany and mycology, which include allelopathy, ecology, taxonomy, physiology etc.
... 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 by its erinacines. Preclinical studies have shown that there can be improvements in Parkinson's, Alzheimer's disease and depression illness, even in ischemic stroke, if H.erinaceus mycelia, enriched with erinacines, are included in daily meals [62,63]. Different clinical trials were carried out with good results. ...
... A double-blinded clinical study showed that the oral administration of H. erinaceus fruiting body was effective in improving mild cognitive impairment in 50-to 80-year-old Japanese patients [63]. Another clinical trial conducted to investigate the effects on dementia found that after 6 months of taking the mushroom, 6 out of 7 patients showed improvement in their perceptual capacities [62]. Endoplasmic-reticulum stress triggers apoptosis on neural cells, being a major cause of degenerative diseases such as Alzheimer´s disease. ...
Article
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Mushrooms are widely used in Asian medicine, both as dietary supplements and as nutraceutical foods. Some principal fungi have recently become popular in Europe for their nutritional and health benefits, and a large number of bioactive compounds have been isolated in several taxa showing antioxidant, anti-inflammatory, antiviral, antitumor activities and other biological properties with great therapeutic application. Separate research has been done separately for the different species. The aim of the present review was to give an overview of the present knowledge regarding bioactive compounds in ten of the most common species, their options in therapeutic use and, for the first time, their possible toxicity or adverse effects. Boletus edulis, Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Hypsizygus marmoreus, Lentinula edodes, Morchella esculenta, Pleurotus ostreatus, Poria cocos and Trametes versicol have great potential as functional foods and as a source of drugs for pharmaceutical science and medicine. Some adverse effects, however, were found to occur in individual daily consumption and during clinical trials. More research is needed to make a good rational use of these medicinal compounds.
... Compounds that exhibit neuroprotective and neuroregenerative activities are the cordycepin from Cordyceps militaris (Cheng et al., 2011), complex carbohydrates and sterols from Ganoderma lucidum (Zhao et al., 2005), lysophosphatidylethanolamine from Grifola frondosa (Nishina et al., 2006), phenol derivatives and diterpene xylosides from Hericium erinaceus (Kawagishi et al., 2008), alkaloids and diterpenes from L. rhinocerotis (Seow et al., 2015) and cerebrosides from Termitomyces albuminosus (Qu et al., 2012). With these findings, it interests us to explore the effects of L. rhinocerotis on functional recovery by using an in vivo model of sciatic nerve crush injury. ...
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Insights into the process of peripheral nerve regeneration are essential for the development of novel therapies. We tested the activity of aqueous extract from Lignosus rhinocerotis mushroom on nerve regeneration in a rat model of sciatic nerve crush injury and to examine (if any) toxicity effect of the extract on nervous tissues. Activities of aqueous extracts were compared to mecobalamin, a drug for peripheral neuropathies. 24 adult rats were randomly divided to 4 groups, the negative controls, positive controls, low and high dosages of aqueous extracts. Functional recovery was evaluated by sensitivity to thermal pain and toe-spreading reflex. Morphological changes in the nervous tissues was assessed by haematoxylin and eosin stain. Hot plate test showed acceleration of sensory recovery in low dosage group compared to other groups. Return of toe-spreading in the crushed limb was accomplished by day 12 and day 16 in low and high dosage groups, respectively after crush injury. Microscopic examination showed normal features of Peripheral and Central Nervous Tissues. There were no abnormal clinical signs detected. Oral administration of low dosage of L. rhinocerotis aqueous extract is capable to enhance motor and sensory functional recovery after nerve injury and had no adverse effects on nervous tissues. Graphical Abstract
... This improvement in the object recognition memory deficit could be attributed to the previously proven effects of several of Antia's ingredients. For example, it has been shown that diosgenin has an antiamyloidogenic effect [27,56] and that Her-icium erinaceus has a strong neuroprotective effect against neuronal loss and dementia in AD [57,58]. Furthermore, oral administration of dried yamabushitake mushroom powder has been demonstrated to effectively improve mild cognitive impairment in humans [19]. ...
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Background: Many neurodegenerative diseases such as Alzheimer's disease are associated with oxidative stress. Therefore, antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Objective: We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer's disease (SAD) induced in mice. Antia is a natural product that is extracted from the edible yamabushitake mushroom, the gotsukora and kothala himbutu plants, diosgenin (an extract from wild yam tubers), and amla (Indian gooseberry) after treatment with MRN-100. Methods: Single intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg) was used for induction of SAD in mice. Antia was injected intraperitoneally (i.p.) in 3 doses (25, 50, and 100 mg/kg/day) for 21 days. Neurobehavioral tests were conducted within 24 h after the last day of injection. Afterwards, mice were sacrificed and their hippocampi were rapidly excised, weighed, and homogenized to be used for measuring biochemical parameters. Results: Treatment with Antia significantly improved mice performance in the Morris water maze. In addition, biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Further studies with western blot showed the protective effect of Antia for the JAK2/STAT3 pathway. Conclusions: Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD.
... Studies have shown that consumption of Hericium erinaceus (lion's mane mushroom) is associated with neurite-stimulating activity through the induction of nerve growth factor (NGF) (in vitro and in vivo) by dilinoleoyl phosphatidylethanolamine (DLPE), hericenones C-H, and erinacines A-I. Preliminary human trials with H. erinaceus derivatives showed efficacy in patients with dementia in improving the Functional Independence Measure (FIM) score or retarding disease progression (Kawagishi & Zhuang 2008), while a double-blind, parallel-group, placebo-controlled trial with oral administration of H. erinaceus to 50-80-year-old Japanese men and women diagnosed with mild cognitive impairment reported significantly increased cognitive function scores compared to placebo during intake (Mori et al. 2009). Therefore, this mushroom has great potential to be developed as a functional food or nutraceutical for boosting brain and nerve health and for improvement of subhealth states related to aging and delaying neurodegeneration. ...
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Mushrooms are becoming a vital component of the human diet for the prevention and treatment of various diseases. The use of mushrooms for developing functional foods, drugs, and nutraceuticals is reviewed in this chapter, with emphasis on present or potential medical implications. As functional foods, mushrooms represent a paradigm of integrating tradition and novelty, due to their wide spectrum of pharmacological properties. Their bioactive components can be extracted or concentrated as nutraceuticals, and/or a diverse class of dietary supplements. Functional foods and nutraceuticals, particularly mushrooms, are immunoceuticals with antitumor and immunomodulatory effects which target and modulate biological processes that foster the development of diseases. Several mushroom products, mainly polysaccharides such as β‐D‐glucans, have proceeded successfully through clinical trials and are used as drugs to treat cancer and chronic diseases. In sum, the present status and future prospects open new avenues for upgrading mushroom species from functional food to translational mushroom medicine.
... Пациенты принимали препарат, который добавляли в пищу, в дозировке 5 г в день. На фоне лечения у пациентов улучшалось общее самочувствие, показатели памяти, внимания, мыслительных операций, возрастала коммуникативная потребность [111]. В 2009 г. опубликованы результаты еще одного двойного слепого плацебо-контролируемого исследования группы профессора Мори (Koichiro Mori), проведенного в клиниках Isogo. ...
... Extensive studies have confirmed the role of erinacines and hericenones in promoting the biosynthesis of NGF (Kawagishi et al., 1996(Kawagishi et al., , 1994 https://doi.org/10.1016/j.jfca.2020.103456 Received 5 October 2019; Received in revised form 10 February 2020; Accepted 15 February 2020 Kawagishi and Zhuang, 2008). In addition to the NGF promoting property, these compounds have been examined for other medicinal effects including their anti-cancer and anti-inflammation properties. ...
... Medicinal properties of Hericium erinaceus (Bull.: Fr) Pers., also known as Lion's Mane, Monkey's Head and Yamabushitake have been well known for hundreds of years in traditional Chinese and Japanese herbal medicine to treat various human diseases. The most promising activity of H. erinaceus is the stimulation of nerve growth factor (NGF) synthesis by hericenones from fruit bodies and erinacines from mycelium (Kawagishi et al., 2008). Extract of fruit bodies exerted neurotrophic action and improved myelination process in mature fibers of neuronal cells in vitro (Moldavan et al., 2007), and promoted normal development of cultivated cerebellar cells as well as regulatory effect on the process of myelin genesis in vitro (Kolotushkina et al., 2003). ...
Article
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Peripheral nerves have the unique capability to regenerate after injury. Insights into regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. We investigated the ability of polysaccharide from Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats by daily oral administration. In sensory functional recovery test, the time taken for the rats to withdraw its hind limb from contact with the hot plate was measured. The test revealed acceleration of sensory recovery in the polysaccharide group compared to negative controls. Further, peripheral nerve injury leads to changes at the remotely located DRG containing cell bodies of sensory neurons. Immunofluorescence studies showed that Akt and p38 MAPK were expressed in DRG and strongly upregulated in polysaccharide group after peripheral nerve injury. The intensity of endothelial cells antigen-1 that recognized endothelial cells in the blood vessels of distal segments in crushed nerves was significantly higher in the treated groups than in the negative control group. Our findings suggest that H. erinaceus is capable of accelerating sensory functional recovery after peripheral nerve injury and the effect involves the activation of protein kinase signaling pathways and restoration of blood-nerve barrier.
... Extracts of Hericium erinaceus revealed terpenoids hericenones and erinacines which show the ability to cross the blood-brain barrier and are active neurotrophic factors particularly effective against neurodegenerative disorders (Mol- davan et al. 2007;Ma et al. 2010;Kawagishi and Zhuang 2008). 3-hydroxyhericenone F has been reported to be active against ER stress dependent neuronal cell death ( Ueda et al. 2008). ...
Article
Mankind has always been fascinated with nature and have heavily explored natural products since the ancient times. Evolution of diseases led to research on synthetic structure, specificity and activity-guided treatment. To combat threats of new developing diseases and the deleterious side effects posed by modern therapy, researchers have once again looked back towards natural resources. Although plants have been the main source of natural drugs, lower fungi are being recently paid attention to. Among them, mushrooms have emerged as an under-explored yet immensely rich resource, especially for bioactive terpenoids. A lot of research is going on around the world with mushroom-derived terpenoids especially their medicinal properties, some of which have even been used in pre- and post-clinical studies. From the literatures that are available, it was found that mushroom terpenoids have activity against a wide range of diseases. In this review, we have summarized different mushroom-derived terpenoids and their therapeutic properties.
... erinaceus) is often consumed and taken as a health supplement in Taiwan, China, and Japan. In Chinese folk medicine, H. erinaceus is used to treat tumors of the digestive system such as esophageal cancer, gastric cancer and duodenal cancer [13,14]. According to various studies, extracts from the fruiting body and mycelium of H. erinaceus provide many health benefits, such as anti-oxidizing properties [15,16], anti-inflammatory properties [17,18], the promotion of neuron growth and regeneration [19][20][21], the prevention of memory loss [22,23], and the activation of other physiological functions. ...
Article
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Previous studies have revealed the anti-inflammatory and neuroprotective properties of Hericium erinaceus extracts, including the fact that the active ingredient erinacine C (EC) can induce the synthesis of nerve growth factor. However, there is limited research on the use and mechanisms of action of EC in treating neuroinflammation. Hence, in this study, the inflammatory responses of human BV2 microglial cells induced by LPS were used to establish a model to assess the anti-neuroinflammatory efficacy of EC and to clarify its possible mechanisms of action. The results showed that EC was able to reduce the levels of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) proteins produced by LPS-induced BV2 cells, in addition to inhibiting the expression of NF-κB and phosphorylation of IκBα (p-IκBα) proteins. Moreover, EC was found to inhibit the Kelch-like ECH-associated protein 1 (Keap1) protein, and to enhance the nuclear transcription factor erythroid 2-related factor (Nrf2) and the expression of the heme oxygenase-1 (HO-1) protein. Taken together, these data suggest that the mechanism of action of EC involves the inhibition of IκB, p-IκBα, and iNOS expressions and the activation of the Nrf2/HO-1 pathway.
... Hericium erinaceus, known as monkey head, lion's mane or pom pom mushroom, is an important edible and medical mushroom which has been used in traditional Chinese medicine for centuries. H. erinaceus extract is used in the prevention and treatment of some diseases such as cancer (Mizuno, 1999), dementia (Kawagishi and Zhuang, 2008), hypercholesterolemia (Liang et al., 2013), hyperglycemia (Hiwatashi et al., 2010). It belongs to the Basidiomycota and grows on hardwoods in nature. ...
Article
The study was carried out to investigate the potential of several kinds of forestry (oak sawdust (OS), poplar sawdust (PS)) and agricultural byproducts (common vessel straw (CV), wheat straw (WS), safflower wastes (SW) and bean straw (BS)) as growing substrate for Hericium erinaceus cultivation, but also assessing the chemical and lignocellulosic changes occurred in the growing substrates during H. erinaceus cultivation process to understand the needs of the fungus. Moreover, the proximate and lignocellulosic composition of H. erinaceus spent mushroom substrate were presented in the study. Among substrates, CV appeared to promote earliness by presenting shorter cropping periods (29 d), whereas maximum yields (115.8 g/kg and 37.3% BE) and heavier basidiomata (54.1 g) were produced by OS substrates. Spawn running time was correlated positively with carbon to nitrogen ratio (C:N) and lignin content of substrates (r 2 = 0.946), while BEs was positively correlated with lignin content (r 2 = 0.846) and inversely correlated to cellulose/ lignin ratio (r 2 =-0.955). The moisture, N, ash, lig-nocellulosic content of all the substrates were changed greatly during H. erinaceus cultivation, but their rates of change varied at different growing stages. The findings indicate that the shortened spawn run period was correlated with the loss of substrate hemicellulose and high lignin concentration in conjunction to their low cel-lulose/lignin ratio applies a positive effect on yield and BEs of H.erinaceus.
... Mushrooms reduce the risk of neurodegenerative diseases [19]. The synthesis of nerve growth factor has been reported from hericenones and erinacines produced by the fruiting body and the mycelium of Hericium erinaceus [54,151]. It has been reported that hispidin, an important medicinal metabolite that belongs to a class of polyphenols that show ROS scavenger properties, was isolated from Phellinus spp. ...
Chapter
Mushrooms are macro‐fungi that bear spores enclosed within a fruiting body. They are a well‐known food for humans and have very important nutritional components. They also have great esthetic, culinary, ecological, and commercial importance. Human survival depends upon food, and humans have consumed mushrooms since prehistoric times because edible mushrooms contain an abundance of vitamin B and other several important minerals; they are also low in calories. Several birds and other animals also consume mushrooms, and thus mushrooms are considered an important component of the terrestrial food chain. However, many mushroom species contain toxins and have caused numerous diseases, and death in rare cases.
... Erinachromane B (2) was obtained as a white amorphous powder. Its molecular formula was determined as C 14 Figure 3). To confirm the planar structure and to determine the absolute configuration of 2, its p-bromobenzoate was prepared for X-ray crystallography analysis. ...
Article
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Three novel compounds, erinachromanes A and B (1, 2), and erinaphenol A (3), along with eight known compounds (4–11) were isolated from the culture broth of Hericium erinaceus. The structures of 1–3 were determined by the interpretation of spectroscopic data. Although compounds 4 and 9 had been synthesized, they were isolated from a natural source for the first time. In the bioassay examining plant-growth regulatory activity, all the compounds suppressed the growth of lettuce.
... Phenolic compounds from Pleurotus ostreatus, Lentinula edodes, or Hypsizygus tessellatus have antibacterial properties as well 17 . However, phenolic compounds occurring in Hericium erinaceus additionally induce the synthesis of a factor that activates the growth and development of nerves 18 . Another equally interesting group of fungal compounds is organic acids. ...
Article
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The aim of this study was to investigate the anticancer and antioxidant activities of low molecular weight subfractions isolated from secondary metabolites produced by the wood degrading fungus Cerrena unicolor. Human colon cancer cells (stage I) HT-29 and human normal colon epithelial cells CCD 841 CoTr were used in the research. The present study demonstrated that the low molecular weight subfractions exhibited inhibitory activity towards human colon cancer cells HT-29 at a concentration range of 25–200 μg/mL. All 6 subfractions inhibited proliferation of cells down to 47.5–9.2% at the highest concentrations in a dose-dependent manner. The most desired activity was exhibited by subfractions S, 3, 4, and 5, as the proliferation of HT-29 cells was inhibited to the greatest extent (16.5, 47.5, 42.7, and 26.1% of the control, respectively), while the effect on CCD 841 CoTr cells was the mildest (inhibition to 54.4, 71.4, 79.4, and 53.4%, compared to the control, respectively). The microscopic observation revealed that all extracts induced programmed cell death, i.e. apoptosis (up to 44.4% (subfraction 6) towards HT-29 and less than 20% (most fractions) towards CCD 841 CoTr), with no or a significantly low level of necrosis in both cell lines at the same time.
... Mushrooms can potentially reduce the risk of neurodegenerative diseases attributing to the high antioxidative capacity of bioactive compounds such as vitamin D and polyphenols (Xu and Beelman 2015). It has been reported that hericenones (A-H) and erinacines (A-K & P-Q), from fruiting bodies and mycelia of H. erinaceus, respectively, induced nerve growth factor synthesis (both in vitro and in vivo) (Kawagishi et al. 2008;Phan et al. 2014). Dai et al. (2010) reported that hispidin, a class of polyphenols, is an important medicinal metabolite from Phellinus spp. ...
Chapter
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Mushrooms have been consumed and appreciated worldwide for their exquisite flavor, nutritional value, and medicinal properties. Some of them being nonedible are known only for their medicinal properties. These organisms belong to a taxonomic group of basidiomycetes or ascomycetes , which produce multiple potential bioactive compounds such as polysaccharides, proteoglycans, terpenes, phenolic compounds, lectins, peptides, and proteins, among others. These bioactive compounds confer to mushrooms’ antioxidant , antimicrobial , antitumor, anti-inflammatory, antineurodegenerative , antidiabetic, anticancer, antidepressant , immunomodulating, and others properties. The increasing isolation and purification of new compounds are leading to the discovering of new therapeutical drugs. However, some of the mushrooms of medicinal importance cannot be cultivated and can be only wild-harvested in the specific growing season, which results in a long time and high cost for producing mushroom bioactive compounds. In this sense, it is very important to improve and optimize conditions for mycelial growth in vitro and create new strains by genetic modification in order to produce large amounts of those compounds of interest. These organisms offer an increasing potential in medical applications due to their chemical composition and a wide range of bioactivities. Most of the reports about biologically active compounds have been focused on in vitro and in vivo (in animal studies) evidence; however, clinical trials need to be carried out.
... Erinacine K showed anti-MRSA activity. 3-Hydroxyhericenone F showed protective activity against endoplasmic reticulum (ER) stressdependent cell death [80,81]. Several ER stress-suppressive compounds were also isolated from scrap cultivation beds of this mushroom [82]. ...
Article
Plants interact with fungi in their natural growing environments, and relationships between plants and diverse fungal species impact plants in complex symbiotic, parasitic, and pathogenic ways. Over the past 10 years, we have intensively investigated plant growth regulators produced by mushrooms, and we succeeded in finding various regulators from mushroom-forming fungi: (1) fairy chemicals as a candidate family of new plant hormones from Lepista sordida, (2) agrocybynes A to E from fungus Agrocybe praecox that stimulate strawberry growth, (3) armillariols A to C and sesquiterpene aryl esters from genus Armillaria that are allelopathic and cause Arimillaria root disease, and (4) other plant growth regulators from other mushrooms, such as Stropharia rugosoannulata, Tricholoma flavovirens, Hericium erinaceus, Leccinum extremiorientale, Russula vinosa, Pholiota lubrica and Cortinarius caperatus.
... It has been reported that a series of benzyl alcohol derivatives hericenones from fruiting bodies and diterpenoid derivatives erinacines from mycelium are promising bioactive substances which are capable of promoting nerve growth factor (NGF) synthesis in vitro and in vivo [77]. However, there is also debate as to whether hericenones are active components stimulating biosynthesis of NGF and recent result have shown that hericenone C, D and E did not increase NGF mRNA expression in 1321N1 human astrocytoma cells [78]. ...
Article
Hericium erinaceus (Bull.) Pers., also known as Yamabushitake, Houtou and Lion’s Mane, is capable of fortifying the spleen and nourishing the stomach, tranquilizing the mind, and fighting cancer. Over the past decade, it has been demonstrated that H. erinaceus polysaccharides possess various promising bioactivities, including antitumor and immunomodulation, anti-gastric ulcer, neuroprotection and neuroregeneration, anti-oxidation and hepatoprotection, anti-hyperlipidemia, anti-hyperglycemia, anti-fatigue and anti-aging. The purpose of the present review is to provide systematically reorganized information on extraction and purification, structure characteristics, biological activities, and industrial applications of H. erinaceus polysaccharides to support their therapeutic potentials and sanitarian functions.
... H. erinaceus is an edible and medicinal fungus consisting of at least 2543 unique proteins, and by differential regulation of biosynthesis genes, this fungus could produce various bioactive metabolites with pharmacological effects (Zeng et al. 2018). Terpenoids, namely, hericenones and erinacines, isolated from H. erinaceus are able to cross the blood-brain barrier (Moldavan et al. 2007;Kawagishi and Zhuang 2008;Ma et al. 2010). Dilinoleoylphosphatidylethanolamine and 3-hydroxyhericenone F compounds isolated from H. erinaceus decrease ER stress-dependent neuronal cell death (Nagai et al. 2006;Ueda et al. 2008). ...
Book
This book spotlights macrofungi with health-promising properties, which mainly belong to Basidiomycota (Agaricomycotina) and Ascomycota (Pezizomycotina). Macrofungi or higher fungi are ascomycetous and basidiomycetous mushrooms forming conspicuous, epigeous, or hypogeous sporocarps and are large enough to be seen by the naked eye. The consumption of wild macrofungi by man goes back 13,000 years. Macrofungi vary in structure and reproduction and occur in a wide range of habitats in different ecogeographic zones of the world. Ethnomycological surveys across the globe reveal the food value and therapeutic significance of wild species in diet and folk medicine. Scientific research proves the nutritional and pharmacological properties of these macrofungi. The latter are consecrated with a wealth of nutrients such as carbohydrates, proteins, fats, fatty acids, amino acids, minerals, and vitamins contributing to their food value. The sporocarps/cultured mycelia or cultured broths of these fungi are rich in numerous high and low molecular weight bioactive constituents. These bioactive components include polysaccharides, proteins, fatty acids, proteoglycans, terpenoids, and phenolics, accounting for a broad spectrum of pharmacological activities such as antioxidant, antitumor, antidiabetic, antibacterial, antifungal, immunomodulatory, antimalarial, and antiviral. Several health-promoting products of macrofungal origin are available in market in the form of tablets, capsules, syrups, pastes, and powders. In spite of huge benefits of macrofungi, these are often overlooked as far as conservation efforts are concerned. Many macrofungal species are red listed by IUCN and need immediate attention to conserve and ensure sustainable use of this inexpensive natural treasure with huge health benefits. In this book, we endeavored to highlight the future prospects of macrofungi and tried to shed light on the taxonomy, ecology, ethnomycology, nutraceutical composition, bioactive active and pharmacological activities, commercialization, and conservation. Some information on cultivation and toxigenic macrofungi is also provided.
... Commercial cultivation of H. erinaceus began in Malaysia two decades ago (Fig. 1) by mainly using abundantly available waste lignocellulosic materials and rubber-wood sawdust. The isolation and characterisation of diterpenoid derivatives, namely hericenones from the fruiting bodies and erinacines from the mycelium [7], have prompted research into using this mushroom as a functional food. ...
Article
Full-text available
Background Hericium erinaceus is a culinary and medicinal mushroom in Traditional Chinese Medicines. It has numerous pharmacological effects including immunomodulatory, anti-tumour, anti-microbial, anti-aging and stimulation of nerve growth factor (NGF) synthesis, but little is known about its potential role in negating the detrimental effects of oxidative stress in depression. The present study investigated the neuroprotective effects of H. erinaceus standardised aqueous extract (HESAE) against high-dose corticosterone-induced oxidative stress in rat pheochromocytoma (PC-12) cells, a cellular model mimicking depression. Methods PC-12 cells was pre-treated with HESAE for 48 h followed by 400 μM corticosterone for 24 h to induce oxidative stress. Cells in complete medium without any treatment or pre-treated with 3.125 μg/mL desipramine served as the negative and positive controls, respectively. The cell viability, lactate dehydrogenase (LDH) release, endogenous antioxidant enzyme activities, aconitase activity, mitochondrial membrane potentials (MMPs), intracellular reactive oxygen species (ROS) levels and number of apoptotic nuclei were quantified. In addition, HESAE ethanol extract was separated into fractions by chromatographic methods prior to spectroscopic analysis. Results We observed that PC-12 cells treated with high-dose corticosterone at 400 μM had decreased cell viability, reduced endogenous antioxidant enzyme activities, disrupted mitochondrial function, and increased oxidative stress and apoptosis. However, pre-treatment with HESAE ranging from 0.25 to 1 mg/mL had increased cell viability, decreased LDH release, enhanced endogenous antioxidant enzyme activities, restored MMP, attenuated intracellular ROS and protected from ROS-mediated apoptosis. The neuroprotective effects could be attributed to significant amounts of adenosine and herierin III isolated from HESAE. Conclusions HESAE demonstrated neuroprotective effects against high-dose corticosterone-induced oxidative stress in an in vitro model mimicking depression. HESAE could be a potential dietary supplement to treat depression.
... In fact, the active components obtained from H. erinaceus, as well as other mushrooms, can be divided into two groups based on their molecular weight [10]. Erinacines and hericenones are representative small molecules with significant neurotrophic and neuroprotective effects and high convenience to cross the BBB [19,20]. Erinacines A-I showed a stronger ability to increase mRNA expression in NGF synthesis than epinephrine as a positive control in murine astroglial cells [21]. ...
Article
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Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6) and one new natural product (2) together with five known compounds (1,3–5,7) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1) and a cyathane diterpenoid, erincine A (3), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells.
... They are reported to induce nerve growth factor (NGF) synthesis, both in vitro and in vivo. However, this medicinal mushroom also has antioxidative, anti-inflammatory, anticancer, immunostimulant, antidiabetic, antimicrobial, hypolipidemic, and antihyperglycemic properties, although its most frequent use is for the treatment of neurodegenerative diseases and cognitive impairment [4,43,44]. ...
Article
Full-text available
Medicinal mushrooms have important health benefits and exhibit a broad spectrum of pharmacological activities, including antiallergic, antibacterial, antifungal, anti-inflammatory, antioxidative, antiviral, cytotoxic, immunomodulating, antidepressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. The growing interest in mycotherapy requires a strong commitment from the scientific community to expand clinical trials and to propose supplements of safe origin and genetic purity. Bioactive compounds of selected medicinal mushrooms and their effects and mechanisms in in vitro and in vivo clinical studies are reported in this review. Besides, we analyzed the therapeutic use and pharmacological activities of mushrooms.
... The effects of hericenone C (1), erinacine A (7), and the extracts of the fungus on dementia were confirmed in animal experiments (Shimbo, Kawagishi and Yokogoshi 2005;Zhuang et al. 2007;Kawagishi and Zhuang 2008;Ratto et al. 2019). ...
Article
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.
... Mushrooms reduce the risk of neurodegenerative diseases [19]. The synthesis of nerve growth factor has been reported from hericenones and erinacines produced by the fruiting body and the mycelium of Hericium erinaceus [54,151]. It has been reported that hispidin, an important medicinal metabolite that belongs to a class of polyphenols that show ROS scavenger properties, was isolated from Phellinus spp. ...
... Studies have shown that consumption of Hericium erinaceus (lion's mane mushroom) is associated with neurite-stimulating activity through the induction of nerve growth factor (NGF) (in vitro and in vivo) by dilinoleoyl phosphatidylethanolamine (DLPE), hericenones C-H, and erinacines A-I. Preliminary human trials with H. erinaceus derivatives showed efficacy in patients with dementia in improving the Functional Independence Measure (FIM) score or retarding disease progression (Kawagishi & Zhuang 2008), while a double-blind, parallel-group, placebo-controlled trial with oral administration of H. erinaceus to 50-80-year-old Japanese men and women diagnosed with mild cognitive impairment reported significantly increased cognitive function scores compared to placebo during intake (Mori et al. 2009). Therefore, this mushroom has great potential to be developed as a functional food or nutraceutical for boosting brain and nerve health and for improvement of subhealth states related to aging and delaying neurodegeneration. ...
Chapter
Full-text available
Mushrooms are becoming a vital component of the human diet for the prevention and treatment of various diseases. The use of mushrooms for developing functional foods, drugs, and nutraceuticals is reviewed in this chapter, with emphasis on present or potential medical implications. As functional foods, mushrooms represent a paradigm of integrating tradition and novelty, due to their wide spectrum of pharmacological properties. Their bioactive components can be extracted or concentrated as nutraceuticals, and/or a diverse class of dietary supplements. Functional foods and nutraceuticals, particularly mushrooms, are immunoceuticals with antitumor and immunomodulatory effects which target and modulate biological processes that foster the development of diseases. Several mushroom products, mainly polysaccharides such as &;#x003B2;&;#x02010;D&;#x02010;glucans, have proceeded successfully through clinical trials and are used as drugs to treat cancer and chronic diseases. In sum, the present status and future prospects open new avenues for upgrading mushroom species from functional food to translational mushroom medicine.
... Secondary metabolites which are capable of protecting and stimulating nerve cells have also been identified. Nerve growth factor stimulators such as Hericenones and erinacines have been isolated from the fruiting body and cultured mycelium of H. erinaceus, respectively (Kawagishi & Zhuang, 2008). Further, Phan et al. (2014) reported that H. erinaceus cultivated in tropical conditions (Malaysia) retained the ability to stimulate neuritogenesis. ...
Article
Ethnopharmacological relevance: Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. Aim of the study: The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. Materials and methods: In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were process and examined for histopathological changes. Results: No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. Conclusion: The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic.
... are also known for their therapeutic potential especially in stimulation or synthesis of nerve growth factor (NGF) and several health-promoting principles including those used in treatment of dementia (e.g. metabolites of H. erinaceus: Kawagishi and Zhuang 2008, Ma et al. 2010, Friedman 2015, Thongbai et al. 2015. It is also known that H. erinaceus possess polysaccharide belonging to -glucan group showing potent antitumor activities (Seok et al. 2009). ...
Article
Full-text available
During inventory of macrofungi in the forests of Western Ghats, two hitherto unrecorded rare hydnoid taxa, Gyrodontium sacchari (Spreng.) Hjortstam (Agaricomycetes, Boletales, Coniophoraceae) and Hericium cirrhatum (Pers.) Nikol. (Agaricomycetes, Russulales, Hariciaceae) were recovered on decaying wood. Both are reported from North-Eastern India, thus the present report constitutes the first report for the Western Ghats of India. This communication embodies brief systematic accounts with illustrations, substrates, distributions and economic value of these hydnoid fungi. Key words: Forest – Gyrodontium sacchari – Hericium cirrhatum – Macrofungi – Western Ghats – Wood
... Reported bioactivities include neuroprotection, anti-cancer and antiinflammation (Kuo et al. 2017;Lee et al. 2016Lee et al. , 2017Lee et al. , 2014Li et al. 2015;Ma et al. 2012;Tzeng et al. 2018). Several studies have found that erinacines and hericenones induced the biosynthesis of nerve growth factor (NGF), a highly conserved protein essentially involved in maintaining and organising neuron function (Kawagishi et al. 1996(Kawagishi et al. , 1994Kawagishi and Zhuang 2008). ...
Article
Full-text available
Hericium novae-zealandiae is a native mushroom traditionally consumed by the indigenous Māori of New Zealand. To study erinacines and hericenones, compounds reported to be unique to the genus Hericium, the small molecular lipophilic constituents of H. novae-zealandiae were evaluated by chromatography coupled with diode array detection. Ethanol was used as an extraction solvent for the detection and quantification of these lipophilic targets. Hericenone C was detected from the ethanol extract of H. novae-zealandiae, but erinacine A and hericenone D were not found present in this extract. A method coupling HPLC with DAD was developed to determine the quantity of hericenone C using a reversed-phase C18 column, with gradient elution consisting of methanol and 0.1% formic acid as mobile phases and detection at 295 nm. The validation conducted of this method included parameters of selectivity, linearity, precision, accuracy and robustness, and all validation results were acceptable. Hericenone C was measured as comprising 0.75 mg/g dry weight of the mushroom. This is the first report of research on erinacine A, hericenone C and hericenone D in H. novae-zealandiae. This is also the first report of an analytical method suitable for the quantification of hericenone C in this species. More compounds unique to Hericium are expected to be reported when further investigations are carried out on this newly studied species of Hericium.
... Erinacines belong to diterpenoids, a kind of secondary metabolites. Several erinacines (i.e., erinacines A-K, P, and Q) were isolated from HE mycelia, among which erinacine A (ErA) was found to be a special compound capable of promoting the performance of nerve growth factor (NGF) [11,12]. So far, ErA found in the mycelia of HE has been confirmed to have pharmacological effects on the central nervous system [13], i.e., long-term prevention of stroke [14], Parkinson's disease [15], Alzheimer's disease [16], depression, and nerverelated diseases such as sexual pain and presbycusis [17]. ...
Article
Full-text available
Hericium erinaceus (HE) is a large edible medicinal fungus. Erinacine A (ErA) is a secondary metabolite presented in the mycelia of HE, with pharmacological effects as a nerve growth factor on the central nervous system. In this study, solid-state cultivation of HE was carried out in Petri dishes and glass jars for the production of mycelial biomass and ErA. The potato dextrose agar (PDA) had the highest mycelial biomass at an optimal temperature of 25 °C, but no ErA was found in the agar media. In glass jar cultivation, the mycelial biomass and specific yield of ErA in different substrates, particle sizes, substrate weights, nitrogen sources, and inorganic salts were investigated. The ErA was purified by a self-pack silica gel column and a semi-preparative HPLC and was identified by liquid chromatography-tandem mass spectrometer. The best conditions for solid-state cultivation of HE when using corn kernel as substrate, particle size less than 2.38 mm, and addition of 10mM ZnSO4, 7H2O, mycelial biomass of 50.24 mg cell dry weight/g substrate was obtained, in addition, the specific yield of ErA could reach 165.36 mg/g cell dry weight.
... Although most studies were conducted on animals, their results are considered to be very promising. The results of preliminary clinical trials also showed that the mushroom was effective in treatment of patients with dementia [99]. ...
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Hericium erinaceum (Bull.: Fr.) Pers. is an edible fungus of great significance in medicine. It is rarely found in Europe, in contrast, it is common in Japan and North America. Its fruitbodies have been well-known for hundreds of years in traditional Chinese medicine and cuisine. A cradle of H. erinaceum cultivation is Asia. In Eastern Europe is rare in natural habitats, but can be successfully cultivated. Both fruitbodies and mycelia are rich in active, health promoting substances. Tests of substances extracted from this mushroom carried out on animals and in vitro have given good results. They can be used in the treatment of cancer, hepatic disorders, Alzheimer’s and Parkinson’s diseases, wound healing. They improve cognitive abilities, support the nervous and immune systems. Promising results have been reported in clinical trials and case reports about the human treatment (e.g., recovery from schizophrenia, an improvement of the quality of sleep, alleviation of the menopause symptoms). The subject of this paper is to summarize information about the development of mycelium, the best conditions for cultivation of fruitbodies, bioactive substances and their use in medicine.
... Many bioactive compounds with medicinal properties have been isolated from HE and identified, e.g., erinacines and hericenones [15]. Both erinacines and hericenones can pass through the blood-brain barrier to the brain and they possess neuroprotective effects [16,17]. Erinacine A (EA) is the main component of the erinacines [15] and it has been shown to have neuroprotective effects against depressive disorder [18], ischemic injury [19], Alzheimer's disease [20,21] and Parkinson's disease in vivo [22]. ...
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Hericium erinaceus (HE) is a common edible mushroom consumed in several Asian countries and considered to be a medicinal mushroom with neuroprotective effects. Erinacine A (EA) is a bioactive compound in Hericium erinaceus mycelium (HEM) that has been shown to have a neuroprotective effect against neurodegenerative diseases, e.g., Parkinson’s disease (PD). Although the etiology of PD is still unclear, neuroinflammation may play an important role in causing dopaminergic neuron loss, which is a pathological hallmark of PD. However, glial cell activation has a close relationship with neuroinflammation. Thus, this study aimed to investigate the anti-neuroinflammatory and neuroprotective effects of EA on lipopolysaccharide (LPS)-induced glial cell activation and neural damage in vitro and in vivo. For the in vitro experiments, glial cells, BV-2 microglial cells and CTX TNA2 astrocytes were pretreated with EA and then stimulated with LPS and/or IFN-γ. The expression of proinflammatory factors in the cells and culture medium was analyzed. In addition, differentiated neuro-2a (N2a) cells were pretreated with EA or HEM and then stimulated with LPS-treated BV-2 conditioned medium (CM). The cell viability and the amount of tyrosine hydroxylase (TH) and mitogen-activated protein kinases (MAPKs) were analyzed. In vivo, rats were given EA or HEM by oral gavage prior to injection of LPS into the substantia nigra (SN). Motor coordination of the rats and the expression of proinflammatory mediators in the midbrain were analyzed. EA pretreatment prevented LPS-induced iNOS expression and NO production in BV-2 cells and TNF-α expression in CTX TNA2 cells. In addition, both EA and HEM pretreatment significantly increased cell viability and TH expression and suppressed the phosphorylation of JNK and NF- κB in differentiated N2a cells treated with CM. In vivo, both EA and HEM significantly improved motor dysfunction in the rotarod test and the amphetamine-induced rotation test and reduced the expression of TNF-α, IL-1β and iNOS in the midbrain of rats intranigrally injected with LPS. The results demonstrate that EA ameliorates LPS-induced neuroinflammation and has neuroprotective properties.
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A new sesterterpene, erinacine S, and one cyathane diterpene xyloside, erinacine A, were isolated from the ethanol extract of the mycelia of Hericium erinaceus. Their structures were elucidated by spectroscopic and X-ray analysis. A 30-day oral course of erinacines A and S attenuated Aβ plaque burden in the brains of 5-month-old female APP/PS1 transgenic mice. Moreover, erinacines A and S significantly increased the level of insulin-degrading enzyme in cerebral cortex.
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Culinary and medicinal mushrooms have been appreciated since prehistoric times as valuable resources for food and medicine. Edible mushrooms represent an untapped source of nutraceuticals and valuable palatable food. Long considered tonics, they are now treasured as functional foods that can improve human health and quality of life. Numerous studies have provided insights into the neuroprotective effects of edible mushrooms, which are attributed to their antioxidant, antineuroinflammatory, and cholinesterase inhibitory properties, and their ability to prevent neuronal death. Here we review the recent literature on the role of culinary and medicinal mushrooms in the management of neurodegenerative diseases and neurotrauma. We highlight some of the molecular mechanisms for how these alternative medicines provide health benefits that could help us to harness their neuroprotective effects.
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Basidiomycetes, a major class of higher fungi adapted to many different climates, habitats, and substrates, have developed a rich and very diverse secondary metabolism. Its products differ in biogenetic origin and structure remarkably from the metabolites of ascomycetes or other prolific producers of secondary metabolites like actinomycetes or myxobacteria. There are, however, some similarities to the products of plants, especially with regard to some polyketides, acetylenes, and sesquiterpenoids. It is noteworthy that many basidiomycete metabolites exhibit interesting biological activities, which in some cases led to the development of very successful plant protectants or antibiotics for human and veterinary uses.
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Chapter
The taxa designated as macrofungi represent a wealth of health-promising fungi rich in a wide spectrum of mycochemicals of nutraceutical and therapeutic value (Wasser 2011; Sanico et al. 2014; Rahi and Malik 2016; Hoeksma et al. 2019). However, only a small fraction out of a vast diversity of fungi in millions (nearly 3–5.1 millions) has been explored for nutrients and therapeutic components. In the last few decades, massive research has been carried out and continues to grow incessantly to explore the biochemistry of macrofungi (De Silva et al. 2013; Flores Jr et al. 2014; Dıaz-Godınez 2015; Badalyan 2016; Kalac 2016; Kivrak et al. 2016; Rathore et al. 2017; Elkhateeb et al. 2019a, b). This is necessary in order to give scientific valorization to the traditional practices of macrofungi especially the medicinal uses. The medicinal species largely belong to the genera Auricularia, Cantharellus, Ganoderma, Pleurotus, Lentinus, Trametes, Tremella, Amanita, etc. and possess a number of high and low molecular weight bioactive constituents responsible for their pharmacological potential (Diksha et al. 2018). Many members of Basidiomycota as well as some of the Ascomycota are rich in antitumor, antimicrobial, antioxidant, hepatoprotective, hypoglycemic, hypolipidemic, immunomodulating as well as prebiotic substances (Lindequist et al. 2010; Chang and Wasser 2012; Giavasis 2013; Mizuno and Nishitani 2013; Wasser 2014; Singh et al. 2017; Chaturvedi et al. 2018; Fernando et al. 2018; Schüffler 2018; Liu et al. 2020). The major bioactive components present in higher fungi are polysaccharides (homo- and hetero-polysaccharides), terpenes (monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids), proteins/peptides, glycoproteins, alkaloids, phenolics, tocopherols, ergosterols, and various fatty acids accounting for their biological activities. These are collectively described as “biological response modifiers” because of their multiple biological impacts which trigger the immune response and elevate the curative properties of the human body (Khatua et al. 2013; Barreira et al. 2014; Kumar 2015; Heleno et al. 2015a; Ruthes et al. 2016; Tel-Cayan et al. 2017; Ma et al. 2018; Phan et al. 2018). The crude extracts and isolated bioactive components from sporocarps and/or mycelial biomass of macrofungi have been appraised for their pharmacological activities. These exhibit anticancer, antidiabetic, anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, hepatoprotective, neuroprotective activities through various metabolic pathways (Thu et al. 2020). However, only a few clinical studies have been performed and need much attention for authentication of the medicinal uses of macrofungi to treat human disorders (Wasser 2017).
Chapter
Mushrooms are used not only for culinary purposes, but also for the treatment of various chronic diseases. It shows vital therapeutic activity in several neurodegenerative disorders such as, Alzheimer's and Parkinson's diseases. These diseases are non-communicable as well as age-related. Currently, no drug therapy is available to treat such neurodegenerative disorders; instead, it is best to delay progression of these diseases. Accumulated evidence has suggested that culinary or medicinal mushrooms may play a significant role in the prevention of these disorders, as mentioned earlier, and dementia. Therefore, daily consumption of mushrooms in the diet may improve memory and cognitive functions, including mushrooms such as, Hericium Erinaceus, Ganoderma lucidium, Pleurotus giganteus, Dictyophora indusiata, Sarcodon scabrosus, Antrodia camphorata Termitomyces albuminosus, Paxillus panuoides, Mycoleptodonoides aitchisonii, Lignosus rhinocerotis, and numerous other species. These mushrooms show potent antioxidative, antiinflammatory, and memory-enhancing activities. This chapter deals with the therapeutic activity of mushrooms and their bioactive components for different neurodegenerative diseases. Thus, mushrooms can be considered supportive and promising candidates for treating or preventing neurodegenerative diseases.
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Researchers have tried various effective treatments that prevent the progressive neurodegeneration of neurons within the brain. Parkinson’s disease (PD), Alzheimer’s disease (AD), and Multiple sclerosis (MS) are some of the most common neurodegenerative diseases (NDDs).Recent Advances in the Treatment of Neurodegenerative Disorders provides interesting updates on treatments of these neurological disorders. Ten chapters have been contributed by experts in pharmacology and give a unique perspective to reader on special topics in this area, including the treatment of neurodegenerative treatment of neurodegenerative disease through ayurveda and phytochemicals, the therapeutic role of vitamins in Parkinson’s disease, mushrooms in NDD treatment, MS treatment, ALS treatment and the use of nanoparticles and nano formulations in NDD treatment. This is an informative reference for pharmacologists, medicinal chemists and healthcare professionals (general practitioners and neurologists) seeking updates in the treatment of some common neurodegenerative disorders.
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In our effort to find antimicrobial agents from higher fungi, we isolated a new compound, dentipellin (1), along with three known glycosylated diterpenes, erinacines A-C (2-4) from culture broth of Dentipellis fragilis. Their chemical structures were determined by spectroscopic methods including NMR and mass measurements. These compounds exhibited weak antibacterial and antifungal activities.
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Chapter
For millennia, edible mushrooms have been used as a common diet for mankind based on their nutritional importance and medicinal benefits. Edible mushrooms are a rich source of carbohydrates (sucrose, xylose, rhamnose, mannose, and fructose), amino acids (glutamic acid, aspartic acid, glutamate, methionine, and cysteine), proteins, fatty acids (linoleic acid, stearic acid, palmitic acid, adrenic acid, and nervonic acid), vitamins (folate, riboflavin, ascorbic acid niacin, thiamine, ergocalciferol, and cyanocobalamine) mineral contents (Ca, Mg, K, P, Na, Fe, Cu, Zn, Cd, and Mo) and phenolic compounds (gallic acid, caffeic acid, protocatechuic acid, p-coumaric acid, p-hydroxybenzoic acid and pyrogallol) that control and ameliorate multiple functions of the human body and participate for maintaining the good health by reducing the occurrence of several chronic diseases. Bioactive polysaccharides, peptides, polyphenols, and dietary fibers extracted from mushroom mycelia have health-promoting properties including a number of medicinal benefits such as anticancerous properties, antihypertensive activity, protection against DNA damage, cardiovascular effects, neurodegenerative disorders, and improvement in innate immunity. In developing countries, the utilization of mushrooms for therapeutic applications is being implemented as a boon for promoting human health and natural dietary supplements. Recently, different pharmaceutical companies and food industries have taken initial steps for patenting the medicinal value of edible mushrooms based on their antioxidant, anticancer, hypolipidemic, hypotensive, and immunomodulatory effects. The immense role of nutritional components and bioactive molecules of edible mushrooms in correlation with health problems has become a burning task in modern nutraceutical therapy. Hence, the present article deals with up-to-date knowledge of edible mushrooms as a nutritional adjuvant with emphasis on profound biological properties and potential mechanisms of action to prevent different health diseases.
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A sialic acid-binding lectin (Hericium erinaceum lectin, HEL), isolated from fresh fruiting bodies of Hericium erinaceum, was treated with various temperature and pH to investigate its fluorescence spectra and hemagglutinating activity. It was found that the hemagglutinating activity of HEL was relatively steady below 60 degreesC and at pH from 6 to 11, and the change of hemagglutinating activity was relative to the change of hydrophobic areas where tryptophan residues located. In fluorescence quenching study of HEL by acrylamide and KI, it was indicated that nearly all the tryptophan residues of HEL located on the surface of the molecule, and most of them were in hydrophobic areas or negatively charged areas. Chemical modification of HEL proved that there were about twelve tryptophan residues in a HEL molecule and all of them were located on the surface or in the shallow groove of the molecule, and eight of them were essential for hemagglutinating activity; aspartic acid or glutamic acid residues were involved in maintaining the crucial conformation of activity center and made great contribution to the hemagglutinating activity of HEL, but they could not touch the sialic acid molecule directly; tyrosine residues also played a role in the hemagglutinating activity of HEL; while arginine, serine, threonine, histidine residues had no effect on the hemagglutinating activity of HEL.
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Two novel compounds, erinacines J (1) and K (3), were isolated from the cultured mycelia of Hericium erinaceum. Their structures were determined by spectral analyses. Erinacine K showed anti-MRSA activity.
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Recent studies have determined that many types of mushroom (eg Hericium spp), may have important physiological functions in humans, including antioxidant activities, the regulation of blood lipid levels and reduction of blood glucose levels. In this study, a methanol extract of the fruiting bodies of Hericium erinaceus was adsorbed on silica gel columns and eluted using polarity gradients of chloroform/ethyl acetate/acetone/methanol. The major components of the extract were D-threitol, D-arabinitol and palmitic acid identified by their chromatographic profiles and spectroscopic characteristics. The methanol extract of H erinaceus was concentrated to remove solvent yielding a residue (referred to as HEM) which was added to the diet. The hypoglycemic effects of feeding HEM to streptozotocin-induced diabetic rats were studied. Polydipsia was stronger in induced diabetic rats not fed HEM than in those receiving HEM. Rats fed with HEM had significantly lower elevation rates of blood glucose level than those not fed with HEM. The effects on blood glucose, serum triglyceride and total cholesterol levels were more significant in the rats fed daily with HEM at doses of 100 mg kg−1 body weight (bw) rather than 20 mg kg−1 bw (p < 0.05). Copyright © 2004 Society of Chemical Industry
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Catecholamines are potent in stimulating nerve growth factor (NGF) synthesis in mouse L-M cells. The relationship between the structure of catecholamines and their stimulatory effect on NGF synthesis has been studied using various 3,4-dihydroxyphenyl derivatives or their analogues. All 3,4-dihydroxyphenyl derivatives with two saturated carbons on the side chain were potent stimulators, whereas those with only one carbon on the side chain were weak stimulators. Drugs lacking the catechol ring were not effective. These results suggest that the catechol part of catecholamines is essential for the stimulatory effect and that the aliphatic side chain potentiates this effect. The present results also suggest the terminal amino residue on the side chain is not critical for the effect.
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A lectin was isolated from the mushroom Hericium erinaceum. This lectin is composed of two different subunits of 15 and 16 kDa and the molecular mass of the intact lectin was estimated to be 54 kDa by gel filtration. It exhibits specificity towards sialic acids, especially N-glycolylneuraminic acid.
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The hypolipidemic effect of an exo-biopolymer produced from a submerged mycelial culture of Hericium erinaceus was investigated in dietary-induced hyperlipidemic rats. Hypolipidemic effects were proportionally increased with the increasing concentration of the exo-biopolymer for oral administration. The exo-biopolymer, at the dose of 200 mg/kg body weight, substantially reduced the plasma total cholesterol (32.9%), LDL cholesterol (45.4%), triglyceride (34.3%), phospholipid (18.9%), atherogenic index (58.7%), and hepatic HMG-CoA reductase activity (20.2%). It increased the plasma HDL cholesterol level (31.1%) as compared to the control group. The molecular mass of this exo-biopolymer measured by HPLC was under 40 kDa. Total sugar and protein contents were 91.2 and 8.8%, respectively. The sugar and amino acid compositions of the exo-biopolymer were analyzed in detail.
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A sialic acid-binding lectin (Hericium erinaceum lectin, HEL), isolated from fresh fruiting bodies of Hericium erinaceum, was treated with various temperature and pH to investigate its fluorescence spectra and hemagglutinating activity. It was found that the hemagglutinating activity of HEL was relatively steady below 60 °C and at pH from 6 to 11, and the change of hemagglutinating activity was relative to the change of hydrophobic areas where tryptophan residues located. In fluorescence quenching study of HEL by acrylamide and KI, it was indicated that nearly all the tryptophan residues of HEL located on the surface of the molecule, and most of them were in hydrophobic areas or negatively charged areas. Chemical modification of HEL proved that there were about twelve tryptophan residues in a HEL molecule and all of them were located on the surface or in the shallow groove of the molecule, and eight of them were essential for hemagglutinating activity; aspartic acid or glutamic acid residues were involved in maintaining the crucial conformation of activity center and made great contribution to the hemagglutinating activity of HEL, but they could not touch the sialic acid molecule directly; tyrosine residues also played a role in the hemagglutinating activity of HEL; while arginine, serine, threonine, histidine residues had no effect on the hemagglutinating activity of HEL.
Article
A laccase with a novel N-terminal sequence, a molecular mass of 63kDa, and inhibitory activity toward HIV-1 reverse transcriptase (IC(50)=9.5microM) was isolated from dried fruiting bodies of the monkey head mushroom Hericium erinaceum. A chromatographic procedure involving ion exchange chromatography on DEAE-cellulose, CM-cellulose, and Q-Sepharose and fast protein liquid chromatography-gel filtration on Superdex 75 was employed. The laccase was adsorbed on DEAE-cellulose and Q-Sepharose but unadsorbed on CM-cellulose. High activity of the enzyme was observed at pH 3-5 and at 50-80 degrees C. Its activity was completely abolished at pH 8 and 9 and after boiling for 10min. A temperature of 50 degrees C and a pH of 5.0 were optimal for its activity.
Article
Alzheimer's disease (AD) is increasing in prevalence, and environmental risk factors have not been identified with certainty. There is evidence that oxidative stress, homocysteine-related vitamins, fats, and alcohol have a role in the pathogenesis of AD. Few large epidemiological studies have explored the associations between nutrients and AD, and there has been only one trial of vitamin E in the prevention of AD. Some studies suggest that high intake of vitamins C, E, B6, and B12, and folate, unsaturated fatty acids, and fish are related to a low risk of AD, but reports are inconsistent. Modest to moderate alcohol intake, particularly wine, may be related to a low risk of AD. Available data do not permit definitive conclusions regarding diet and AD or specific recommendations on diet modification for the prevention of AD.
Article
Hericium erinaceum is a medicinal and edible mushroom with anti-microbial and anti-cancer activities. To evaluate the immunoregulatory functions of H. erinaceum, we prepared water extract from H. erinaceum (WEHE) and investigated its ability to activate macrophages and to induce nitric oxide (NO) production in macrophages. Rat peritoneal macrophages stimulated with 1 to 100 mug/ml of WEHE for 24, 48, or 72 h produced NO in a time- and dose-dependent manner. Reverse transcription-polymerase chain reaction demonstrated that WEHE augmented the steady-state level of inducible NO synthase (iNOS) mRNA in both the peritoneal macrophages and a murine macrophage cell-line, RAW 264.7. Electrophoretic mobility shift assay showed that WEHE increased DNA binding activity of the transcription factor NF-kappaB, which is responsible for iNOS gene expression. Furthermore, its trans-acting activity was confirmative as determined by in vitro transfection assay using a reporter gene construct, p(NF-kappaB)(3)-CAT, whose expression is solely regulated by the activity of NF-kappaB. Concomitantly with the activation of NF-kappaB, WEHE markedly decreased intracellular IkappaBalpha level as demonstrated by Western blot assay. These results suggested that WEHE induces iNOS gene expression followed by NO production in macrophages via enhancing the activation of transcription factor, NF-kappaB.
Article
To investigate the inductive effect of water extract from Hericium erinaceum (WEHE) on interleukin-1beta (IL-1beta) expression. A murine macrophage cell-line, RAW 264.7 was stimulated with 1 to 10 mg/L WEHE and inductions of IL-1beta protein and its steady state mRNA were examined using a bioassay, Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The inductive effect of WEHE on IL-1beta gene expression was further investigated by a chloramphenicol acetyltransferase (CAT) reporter gene assay using a transient transfection with pIL-1(870 bp)-CAT where the expression of the CAT gene was regulated by a IL-1beta promoter. An electrophoretic mobility shift assay (EMSA) was also performed to examine transcription factors, nuclear factor-kappa B (NF-kappaB), activator protein 1 (AP-1), nuclear factor interleukin-6 (NF-IL6), and cAMP response element (CRE)/activating transcription factor (ATF). WEHE induced IL-1beta production in both its mRNA and protein expression in a dose-dependent manner. The inductive effect of WEHE on IL-1beta gene expression was due to the augmentation of the IL-1beta transcription. Furthermore, EMSA showed that WEHE markedly increased the binding activities of NF-kappaB, and to a lesser extent, those of AP-1 and NF-IL6 to their cognate DNA recognition sites, whereas CRE/ATF binding remained constant, all of which are known to be involved in the regulation of IL-1beta gene expression. WEHE induces IL-1kappa expression in macrophages at a transcriptional level by enhancing the activation of transcription factors, NF-kappaB, NF-IL6, and AP-1.
Article
To investigate the immunoregulatory functions of water extracts of Hericium erinaceum (WEHE) focusing on natural killer (NK) cell-based anticancer activities. Mouse splenocytes or purely isolated NK cells were stimulated with 1-100 mg/L WEHE for 24 h followed by co-culture with (51)Cr-labeled Yac-1 cells for 4 h, then NK cell-derived cytolytic activity was measured using a radio-release assay. Neutralizing antibodies against mouse interleukin-12 (IL-12) were added into the WEHE-stimulated splenocytes, thereafter, cytotoxicity was measured to examine the involvement of IL-12. RT-PCR and ELISA analyses were performed to confirm the induction of transcription and the translation of IL-12 and interferon-gamma (IFN-gamma) in the WEHE-treated splenocytes. WEHE enhanced the cytolytic activity of total splenocytes towards Yac-1 cells in a dose-dependent manner. However, this activation was not observed when the NK cells isolated from the splenocytes were treated with WEHE. Furthermore, the treatment with antibodies against IL-12 abolished the effect of WEHE on splenocyte-derived cytolytic activity. RT-PCR and ELISA analyses showed the induction of IL-12 and IFN-gamma in the WEHE-treated splenocytes. WEHE indirectly activates the cytolytic ability of NK cells via the induction of IL-12 in total splenocytes, and possibly via other immuno-mediators or cellular components.
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