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猴头菌小分子活性成分研究进展



全 文 :食用菌学报2012.19(1):79~84
收稿日期:2011-11-08原稿;2012-01-25修改稿
基金项目:国家基础研究重大研究计划(973)(编号:2012CB721102)、国家自然科学基金 (编号:30830002)、香港中
文大学李嘉诚健康科学研究所基金 (编号:7103506)、上海科技兴农重点攻关项目[编号:沪农科攻字
(2009)第2-2号]的部分研究内容
作者简介:尚晓冬(1973-),男,中国科学院植物生理生态研究所在读博士,副研究员,从事食用菌遗传育种工作。
E-mail:xdshang@163.com
文章编号:1005-9873(2012)01-0079-06
猴头菌小分子活性成分研究进展
尚晓冬1,2,王国艳1,潘 伟1,孙 蓉1,蔡艳华1,谭 琦1,赵国屏2
(1上海市农业科学院食用菌研究所,农业部南方食用菌资源利用重点实验室,国家食用菌工程技术研究中心,
国家食用菌加工技术研发分中心,上海市农业遗传育种重点开放实验室,上海201403;
2中国科学院植物生理生态研究所,上海200032)
摘 要:综述猴头菌(Hericium erinaceus)小分子活性成分的研究进展,旨在为这类物质的进一步开发利用提
供参考。
关键词:猴头菌;小分子物质;含芳香环化合物;吡喃酮化合物;甾醇化合物;生物活性
  作为一种食药两用真菌,猴头菌(Hericium
erinaceus)味甘、性平,有利五脏、助消化、滋补、
抗癌等功能。在我国,猴头菌主要用于治疗慢性
胃炎[1,2]。以猴头菌固体发酵菌丝体为原料生产
的“猴头菇菌片”自1977年于上海市获批投产以
来,已经成为国内治疗消化道溃疡、炎症的主要
药物之一。长期、大量的临床应用表明,除对慢
性胃炎外,猴头菌片单独或辅助其它化学药物,
对消化不良[3,4]、溃疡性结肠炎[5,6]、胃和十二指
肠溃疡[7-10]、上消化道恶性肿瘤[4,11]等多种消化
系统疾病也有确切良好的疗效,长期服用安全有
效,极少发现不良反应和毒副作用。目前我国有
100多个以猴头菌为主要原料的用于胃肠疾病治
疗的准字号药。此外,民谚还有“多食猴头,返老
还童”之说。国外研究表明,猴头菌对另一重要
疾病———痴呆症也显示出良好的防治效果,双盲
试验结果表明,猴头菌粉能改善轻度的认知障
碍[2],同时还发现猴头菌粉可防止记忆和学习能
力的损害[13]。关于猴头菌小分子活性成分的基
础研究,迄今为止国内外已经发现数十种,主要
包括 含 芳 香 环 类 的 hericenones,二 萜 类 的
erinacines,甾醇类(sterols)和脂肪酸及其酯类
等。这些化合物具有刺激神经生长因子(nerve
growth factor,NGF)合成、抗炎、抗癌、抑菌等广
泛的生物活性。本文简要综述目前该领域的研
究进展。
1 含芳香环类化合物
  根据发现者命名的不同,从猴头菌中发现的
含 芳 香 环 类 化 合 物 可 分 为 hericenones、
erinacerin、hericerin和hericene,它们具有类似的
化学结构。
1.1Hericenones
  其中hericenones是第一类被发现的对神经
生长因子的生成具有刺激作用的天然产物,其效
果相当于肾上腺素。从猴头菌中发现这些化合
物意义重大,可能为治疗或改善日趋严重的痴呆
症带来新的希望,是猴头菌功能中除治疗胃病外
另一 重 要 的 发 现。从 1990 年 发 现 第 一 个
hericenone开始到2008年为止,人们已经在猴头
菌中 发 现 了 11 种 hericenone。最 先 发 现 的
hericenone A和hericenone B虽然没有显示出刺
激神 经 生 长 因 子 的 活 性,但 它 们 分 别 可 在
100μg/mL和6.3μg/mL时完全杀死子宫颈癌
HeLa细胞[14]。hericenone C、hericenone D、
hericenone E、hericenone F、hericenone G 和
hericenone H则相反,未显示出细胞毒活性,却
都能刺激大鼠的星形细胞(astroglial cel)NGF
的合成,并且抑制前列腺素(prostaglandin)E2的
产生[15-17]。MORI等还发现hericenone B选择
食 用 菌 学 报 第19卷
性抑制胶原蛋白诱导的血小板凝集,体外实验中
IC50约为3μmol/L,具有预防血栓形成的潜在价
值[18]。UEDA 等[19] 从 猴 头 菌 中 得 到 3 个
hericenones : 3-hydroxy-hericenone  F、
hericenone I 和 hericenone J。3-hydroxy-
hericenone F具有保护神经瘤细胞系 Neuro 2a
免受依赖于内质网应激而死的活性,hericenone
I和hericenone J则无此活性。MORI等[20]研究
了刺芹侧耳(杏鲍菇,Pleurotus eryngii)、灰树花
(Grifola frondosa)、巴西蘑菇(姬松茸,Agaricus
blazei)和猴头菌的乙醇提取物对人astrocytoma
细胞神经生长因子基因表达的影响,发现只有猴
头菌提取物能通过激活JNK (c-jun N-terminal
kinase)途径促进神经生长因子表达与分泌,但起
作 用 的 不 是 hericenone C ~ E,或 者 说
hericenone C~E不是通过激活JNK途径而起
作用。
1.2Erinacerins
  YAOITA等[21]从猴头菌子实体中分离得到
与hericenone结构相似的化合物erinacerin A和
erinacerin B。目前尚无有关这两化合物生物活
性的报道。
1.3Hericerin
  Hericerin是从猴头菌的子实体中分离得到
与hericenone B结构相似的化合物,区别仅在于
hericerin 的 5’位 置 缺 少 羰 基。hericerin 在
100mg/L时,完全抑制松花粉萌芽,显著抑制茶
花粉芽管生长[22]。
1.4Hericenes
  ARNONE等人[23]从猴头菌中还分离得到
有弱细胞毒性的hericene A、hericene B、hericene
C,它们的结构分别与hericenone C~E相似,区
别在于5’位置缺少羰基。这种结构上的变化对
活性的影响尚不清楚。
2 二萜类化合物(Erinacines)
  在试图以菌丝发酵代替猴头菌子实体生产
来获得更大量的hericenones的过程中,意外在
菌丝体中发现另一类化合物———erinacines,这种
二萜类化合物多数同样能够刺激细胞或小鼠神
经生长因子的合成。
KAWAGISHI等 [24]首先从猴头菌丝中分
离得到erinacine A、erinacine B及erinacine C,随
后又 陆 续 得 到 erinacine E、erinacine F 和
erinacine G[25],这些结构独特的化合物均能强烈
刺激神经生长因子合成。此后,他们又发现两种
新的二萜类化合物erinacine J和erinacine K,并
发现erinacine K、erinacine A和erinacine C对耐
甲氧西林金黄色葡萄球菌(methicilin-resistant
Staphylococcus aureus,MRSA)有抑菌活性,而
erinacine J 和 erinacine E 不 显 示 活 性[26,27]。
SAITO等[28]从分枝猴头菌(hericium ramosum)
菌株CL24240中也分离得到erinacine E,并发现
其是一种高选择性的κ受体激动剂(κreceptor
agonist)。SHIMBO等[29]发现经erinacine A处
理的大鼠蓝斑(locus coeruleus)去甲肾上腺素
(norepinephrine)及香草酸(homovanilic acid)
水 平 提 高,进 而 增 加 蓝 斑 和 海 马 区
(hippocampus)的神经生长因 子 产 生。LEE
等[30]从猴头菌菌丝中分离得到erinacine H 和
erinacine I,并发现33.3μg/mL的erinacine H
可以使大鼠的星形细胞 NGF分泌增加5倍以
上,达到 (31.5±1.7)pg/mL。KENMOKU
等[31,32]在2000年和2002年先后发现erinacine
P和erinacine Q,有证据显示它们是erinacine C
生物合成途径中的中间产物。MA 等[33]于2008
年发现erinacine R,但未见相关活性报道。
3 吡喃酮类化合物(Erinapyrones)
  Erinapyrone A和erinapyrone B是最先得到
erinapyrone序列命名的两个猴头菌吡喃酮化合
物,对 HeLa 细 胞 有 细 胞 毒 性[34]。 但 是
erinapyrone A和erinapyrone B并不是最早从猴
头菌中被分离出来的吡喃酮类化合物。我国的
钱伏刚等[35]在1990年首先从猴头菌中分离出两
个吡喃酮化合物,分别命名为herierinⅢ和Ⅳ;这
两个化合物再次于2000年被我国台湾的周友诚
分得,但herierinⅢ被命名为erinapyrone D [17],
同时将 herierin Ⅳ 误认为是由意 大 利 学 者
ARNONE[23]于1994年从猴头菌中分离出的
erinapyrone C,并 认 为 他 得 到 的 这 个
“erinapyrone C”(实为herierinⅣ)可促进第一型
星状神经胶质细胞(type I astrocytes)的增生[17]。
而ARNONE发现的真正的erinapyrone C对革
兰氏阳性细菌有弱的抑菌活性。OMOLO等[36]
从与 猴 头 菌 系 统 发 育 关 系 很 近 的 韧 革 菌
(Stereumsp.)中也得到过erinapyrone C。
08
第1期 尚晓冬,等:猴头菌小分子活性成分研究进展
4 甾醇类化合物(Sterols)
  麦角甾醇(ergosterol)是真菌类的特征甾醇,
是治疗真菌感染的药靶之一,主要以游离状态存
在于真菌中[37],可以用于标记真菌的生物量[38]。
食用菌中普遍含有麦角甾醇和过氧麦角甾醇等
甾醇类化合物[39,40]。KRZYCZKOWSKI[41]、周
友诚[17]和李洁莉[42]等曾从猴头菌菌丝和子实体
中均分离到麦角甾醇和过氧麦角甾醇。甾醇类
化合物尤其是麦角甾醇具有抗炎、抗癌等生物活
性[43]。麦 角 甾 醇 还 是 vitamin D2 的 前 体,
vitamin D2有助于预防前列腺癌和结肠癌[44]。
TAKAKU等[45]研究发现,姬松茸子实体中的麦
角甾醇能够抑制肿瘤引起的血管增生。TAKEI
等的研究表明过氧麦角甾醇能抑制某些癌细胞
生长和凋亡[46]。
5 其它小分子化合物
  宋慧等[47]从小刺猴头菌(Hericium caput-
medusae)中分离鉴定出18种脂肪酸及其衍生
物,绝大多数为脂肪酸酯类化合物,其中十八碳
烷烃链化合物占多数,达7种之多,包括硬脂酸、
油酸、亚油酸、亚麻酸等,相对含量达40.44%。
十至十八碳炔酸酯是小刺猴头菌子实体石油醚
相中的重要成分,相对含量高达14.31%,另外从
猴头菌中还得到赤藓糖醇、葡萄糖醇、木糖醇等
糖醇类化合物。曹瑞敏等[48]检测到猴头菌子实
体中含有3种脂肪酸成分:亚油酸、十六烷酸乙
酯、乙基亚油酸。NAGAI等发现双亚麻油酸磷
酯 乙 烯 胺 (dilinoleoyl-phosphatidylethanola-
mine,DLPE)具有与3-hydroxy-hericenone F类
似的降低Neuro 2a细胞内质网压力依赖的死亡
率 的 活 性[49]。 周 友 诚 分 离 出 神 经 酰 胺
(ceramide)[17]。
6 猴头菌粗提物的其它生理活性
  除了以上提到的化合物及相关活性外,已报
道的猴头菌生物活性更多是关于其粗提物的。
刘浩等[50]发现猴头菌提取物能改善衰老小
鼠的学习记忆能力,有效延缓模型衰老小鼠衰老
体征的出现,该作用可能与其清除自由基、改善
衰老相关酶作用有关。何苗等[51]通过 Morris水
迷宫试验发现,小刺猴头菌醇提物(EHCP)可使
阿尔茨海默病(Alzheimers disease)AD模型鼠
的寻找潜伏期分别由第3天的(48.7±35.5)s和
第4天的(49.5±32.1)s缩短至(18.5±7.2)s
和(15.4±9.2)s(P<0.05);酶学检测结果表明
EHCP可升高 AD模型鼠脑内 AchE活性(P<
0.05):免疫组化结果显示EHCP可增加模型鼠
脑内NGF蛋白表达水平(P<0.01),这些结果表
明猴头菌醇提取物可有效提高AD小鼠的判断及
记忆能力,其机制可能与保护神经细胞及促进神
经细胞再生等有关。HAZEKAWA等[52]发现提
前14d服用猴头菌可以增加模型鼠脑内NGF的
水平,保护小鼠脑动脉栓塞引起的局灶性脑缺
血,显示出猴头菌在预防脑梗塞中的价值。
HIWATASHI等[53]发现在小鼠的高脂饮食中加
入2%的猴头菌醇提取物可以显著改善试验动物
的体重和降低脂肪、血及肝中甘油三酯的水平,
而热水提取物无此作用。于成功等[54]观察到猴
头菌对乙醇导致的大鼠胃粘膜损伤具有预防和
治疗作用:可明显减轻胃粘膜的充血、出血,水肿
和坏死,减轻炎细胞浸润,促进粘膜氮基己糖的
恢复,防止胃泌素的升高。向前等[55]观察到猴头
菌提取物可缩短便秘小鼠的每天首次排便时间,
增加便秘小鼠的排便次数和排便重量。林海鸣
等[8]发现猴头菌可降低无水乙醇致小鼠胃溃疡
指数;降低醋酸致大鼠胃溃疡指数,对大鼠血清
中超氧化物歧化酶(superoxide dismutase,SOD)
的活性和丙二醛(malondialehyde,MDA)水平没
有显著影响。这些初步的观察研究表明,猴头菌
提取物能改善模型动物的病理变化。
7 猴头菌的抗菌活性
  关于猴头菌抗菌的研究不多。OKAMOTO
等曾分离到有抗菌活性的地衣酚类(chlorinated
orcinol derivative)物 质[56]。张 庭 廷 等[57] 和
WONG等[58]分别观察到猴头菌的制备物能抑制
某些致病菌的生长。在自然环境中,真菌需要对
抗无处无时不在的其它微生物的威胁,它们能够
产生种类繁多的有助于人类的抗菌成分并不令
人意外[59-64]。
8 展望
  我国猴头菌片开发和应用历史有35年之
久,当时一个新药品上市的标准与如今相比已经
不可同日而语,似乎也没有必要再对这个老药补
上符 合 国 际 标 准 (如 National Institutes of
18
食 用 菌 学 报 第19卷
Health,NIH)的有关毒性、量效等数据。但人们
对猴头菌活性成分的了解相对于它的应用而言,
还远远不够,很多应用的物质基础尚未明确,对
它真正的药效成分却不能永远“敬而远之”。目
前对猴头菌的临床或生理活性的研究结果大部
分是以猴头菌粗提取为材料得到的,其多样化的
生物活性的成分归属均不明确,这不但限制了开
发效果更好的新产品,对原有产品的质量控制也
不利。结合慢性胃炎等疾病研究的最新进展,以
新的思路开展猴头菌活性成分的研究,可望使
“猴头菌片”这棵老树开新花,更好地服务人类
健康。
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[本文编辑] 于荣利
48
ACTA EDULIS FUNGI2012.19(1):85~91
Received:Nov.8,2011; Accepted:Jan.25,2012
Supported by the National Basic Research Program (973)(No.2012CB721102),National Nature Science
Foundation(No.30830002),Li Ka Shing Foundation,The Chinese University of Hong Kong(No.7103506),
Foundation of the Shanghai Government(Hunonggong2002:No.2-2)
  E-mail:xdshang@163.com
犃犱狏犪狀犮犲狊犻狀犚犲狊犲犪狉犮犺狅狀犔狅狑犕狅犾犲犮狌犾犪狉犠犲犻犵犺狋
犅犻狅犪犮狋犻狏犲犆狅犿狆狅狀犲狀狋狊狅犳犎犲狉犻犮犻狌犿犲狉犻狀犪犮犲狌狊
SHANG Xiaodong1,2,WANG Guoyan1,PAN Wei 1,SUN Rong1,CAI Yanhua1,
TAN Qi 1,ZHAO Guoping2
(1Institute of Edible Fungi,Shanghai Academy of Agricultural Sciences;Key Laboratory of Edible Fungi
Resources and Utilization(South),Ministry of Agriculture,P.R.China;National Engineering Research Center
of Edible Fungi;National R&D Center for Edible Fungi Processing;Key Laboratory of Agricultural Genetics and
Breeding of Shanghai,Shanghai 201403,China;2Institute of Plant Physiology and Ecology,
Chinese Academy of Sciences,Shanghai 200032,China)
Abstract:Advances in research on low molecular weight bioactive components of Hericium erinaceus have
been reviewed to provide a source of reference for the further development and utilization of these
components.
Key words:Hericium erinaceus;low molecular weight bioactive component;aromatic compound;erinacines;
erinapyrones;sterols;biological activity
    The edible and medicinal fungus,
Hericium erinaceus,has long been recognized
to have a favorable effect on the internal
organs of the body.In China,it has been used
to aid digestion,as a cure for chronic gastritis,
and as an anti-cancer treatment[1,2]. H.
erinaceus Tablet has been one of the main
medicines used in China to treat gastrointestinal
ulcers and inflammation since it was first
produced in Shanghai in 1977.Long-term
observations and a large number of clinical
applications have shown that H.erinaceus
Tablet,either alone or in combination with
other compounds, was effective in the
treatment of many conditions affecting the
digestive system including indigestion
[3,4],
ulcerative colitis[5,6],gastric and duodenal
ulcers[7-10] and  upper  gastrointestinal
malignancies[4,11].It is considered safe and
effective for long-term use,and few adverse
reactions or side effects have been reported.
Currently,H.erinaceus is the main raw
material used in the production of more than
100licensed drugs for treating gastrointestinal
diseases,and is the subject of the Chinese
proverb“Eat more H.erinaceus and become
young again”. Researchers in Japan have
reported that H.erinaceus has a beneficial
effect on dementia[12],and a double-blind trial
revealed that powdered H.erinaceus mycelium
improved mild cognitive impairment and
prevented memory loss and learning ability
[13].
To date,dozens of low molecular weight
components of  H. erinaceus, including
hericenones,erinacines,sterols,fatty acids
and esters have been tested and shown to
exhibit a wide range of biological activities
including stimulation of nerve growth factor
synthesis,as wel as anti-inflammatory,anti-
cancer and anti-bacterial properties. This
ACTA EDULIS FUNGI  Vol.19
article summarizes the recent progress of
research into these low molecular weight active
components.
1 Aromatic compounds
  Aromatic  compounds  reported  in
H.erinaceus can be divided into hericenones,
erinacerins,hericerin and hericences,al of
which have similar chemical structures.
1.1Hericenones
  Hericenones were the first class of natural
products found to stimulate the synthesis of nerve
growth factor (NGF)in a similar way to
epinephrine.Discovery of these compounds in H.
erinaceus brought new hope for dementia suferers,
and extended the list of functions attributed to H.
erinaceus beyond the treatment of stomach
ailments.Between 1990(when the first hericenone
was reported)and 2008,11hericenones had been
described.Although hericenone A and hericenone B
were not active in stimulating NGF synthesis,they
kiled cervical cancer HeLa cels at 100μg/mL and
6.3 μg/mL concentrations, respectively
[14].
Conversely, whereas  hericenones  C-H
exhibited no cytotoxic effects,they stimulated
the synthesis of NGF by rat astroglial cels and
inhibited the production of prostaglandin
E2[15-17].MORI also found that hericenone B
selectively inhibited in vivo colagen-induced
platelet aggregation with an IC50value of~3
μmol/L,indicating potential for preventing
thrombosis[18].UEDAet al reported three new
hericenones: 3-hydroxy-hericenone  F,
hericenone I and hericenone J,of which 3-
hydroxy-hericenone F protected the neuroma
cel line Neuro 2a from death induced by
endoplasmic reticulum (ER)stress[19].MORI
et al studied the effects of ethanol extracts of
Pleurotus eryngii,Grifola frondosa,Agaricus
blazei and H.erianaceus on NGF gene
expression in human astrocytoma cels.Only
H.erinaceus extracts increased NGF gene
expression and secretion through stimulation of
c-Jun N-terminal kinase(JNK),but this direct
effect was not caused by hericenones C-E
[20].
1.2Erinacerins
  YAOITAet al isolated erinacerins A and B
from H.erinaceus fruit bodies. However,
although similar in structure to hericenones,no
biological activity has so far been attributed to
these two compounds[21].
1.3Hericerin
  Isolated from H.erinaceus fruit bodies,
hericerin is similar in structure to hericenone B
but lacks the carbonyl group at the 5’-position.
At  100 mg/L  concentration, hericerin
completely inhibited the germination of pine
polen and significantly inhibited the growth of
tea polen germ tubes[22].
1.4Hericenes
    ARNONE et al isolated the weakly
cytotoxic hericenes A,B and C from H.
erinaceus mycelium.Similar in structure to
hericenones C,D and E,respectively (each
lacking a carbonyl group at the 5’position),the
effect of this structural difference on bioactivity
is stil unclear[23].
2 Erinacines
    Erinacines were identified accidentaly
during  attempts  to  increase  hericenone
production by H.erinaceus mycelium grown in
fermenters. KAWAGISHI et al isolated
erinacines A,B,C,E,F and G,al of which
strongly stimulated the synthesis of NGF[24,25],
and two additional compounds,erinacines J and
K. Erinacines K, A and C exhibited
antibacterial  activity  towards  methicilin-
resistant Staphylococcus aureus (MRSA)[26,27].
SAITO reported that erinacine E,isolated from
a strain of H.ramosum (CL24240),was a
highly selectiveκ-opioid receptor agonist[28].
SHIMBO et al found that administration of
erinacine A to rats increased the levels of locus
coeruleus (LC ) norepinephrine  and
homovanilic acid,which resulted in increased
levels of  NGF  in  the  LC  and  the
68
No.1 SHANG Xiaodong,WANG Guoyan,PAN Wei,et al
hippocampus[29].LEE et al isolated erinacines
H and I from H.erinaceus mycelia and
reported that the former increased NGF
secretion by rat astroglial cels more than5-fold
(to 31.5±1.7 pg/mL)[30].KENMOKU et al
identified erinacines P and Q as intermediates
in the biosynthetic pathway of erinacine
C[31,32].More recently,MA et al identified
erinacine R but,as yet,no bioactivity has been
assigned to this compound[33].
3 Erinapyrones
  Erinapyrones A and B were isolated from
cultured H.erinaceus mycelia by KAWAGISHI
et al and shown to exhibit cytotoxicity[34].
However,the first two pyrone compounds to be
isolated from H.erinaceus,by QIANet al in
1990[35],were designated herierins III and IV.
These two compounds were described again by
ZHOU in Taiwan,and herierin III was renamed
erinapyrone D[17]. Herierin IV, mistakenly
thought by ZHOU to be identical to the
erinapyrone C isolated by the Italian researcher
ARNONE  in  1994[23], promoted  the
proliferation  of  type  I  astrocytes[17].
Erinapyrone C described by ARNONE was
weakly  inhibitory  towards  Gram-positivie
bacteria. OMOLO and STERNER[36] also
isolated erinapyrone C from a Stereum sp.,
which is closely related phylogeneticaly to H.
erinaceus.
4 Sterols
  Ergosterol occurs in the free state in fungal
cel membranes. The sterol serves as a
determinant of fungal biomass[37]and,as such,
can be used to evaluate the efficacy of treatments
for fungal infections[38].Edible fungi generaly
contain ergosterol and peroxy ergot sterols[39,40].
Ergosterol and peroxy ergot sterols have been
isolated from mycelia and fruit bodies of H.
erinaceus by KRZYCZKOWSKI[41],ZHOU[17]
and LI[42].Sterols,especialy ergosterol,are
reported to exhibit anti-inflammatory and anti-
cancer activities[43]. Ergosterol is also a
precursor of vitamin D2,which is thought to
prevent cancers of the prostate and colon[44].
TAKAKU et al reported that the anti-tumor
effect of ergosterol from Agaricus blazei fruit
bodies was due to the inhibition of tumor-
induced angiogenesis[45].TAKEI et al reported
that peroxy ergot sterol inhibited the growth of,
and induced apoptosis in, certain cancer
cels[46].
5 Other low molecular weight compounds
   SONG et al isolated and identified 18
different fatty acids and their derivatives from
H.caput-medusae,mostly fatty acid esters,
and the majority (40.44%)were 18-carbon
alkyl chain compounds including stearic,oleic,
linoleic and linolenic acids.Alkyne esters(10to
18 carbons)amounted to 14.31% of the
petroleum ether phase from Hericium caput-
medusae fruit bodies. Linoleic acid,ethyl
linoleic acid and hexadecanoic acid ethyl ester
were isolated from H.erinaceus fruit bodies by
CAO et al[47].H.erinaceus has also been
reported to contain ceramide[17],erythritol,
glucose,alcohols,xylitol and other sugar
alcohols[48]. NAGAI et al reported that
dilinoleoyl-phosphatidylethanolamine (DLPE)
from H.erinaceumprotected against ER stress-
dependent Neuro 2acel death via the protein
kinase C pathway[49].
6 Bioactivities associated with crude
extracts of H.erinaceus
    In addition to the aforementioned
compounds,various biological activities and
improvements in the pathological symptoms of
animal models have been associated with crude
extracts of H.erinaceus.LIU and LI[50]
reported that extracts of  H. erinaceus
improved the learning ability and memory,as
wel as delaying the onset of ageing signs,in a
mouse model.The authors suggested these
effects were related to free-radical scavenging
78
ACTA EDULIS FUNGI  Vol.19
activity and enhancement of anti-ageing enzyme
activities. Ethanol extracts of H.caput-
medusae(EHCP)reduced escape latency times
in the Morris water maze test from (48.7±35.
5)s to(18.5±7.2)s on the third day,and
from(49.5±32.1)s to(15.4±9.2)s on the
fourth day,in Alzheimer’s disease(AD)model
mice[51].EHCP increased acetylcholine esterase
activity  in  the  AD  model  mice, and
immunohistochemical data revealed that EHCP
increased the expression level of NGF protein.
Ethanolic extracts of  H. erinaceus also
improved judgement and memory ability in AD
mice by a mechanism that may be related to
preventing  degeneration, and  promoting
regeneration,of nerve cels.HAZEKAWA et
al[52] reported that intake of H.erinaceus
increased NGF levels in the brains of a mouse
model and prevented focal cerebral ischemia
caused by arterial embolism,thereby indicating
possible value in averting cerebral infarction.
HIWATASHI et al[53] reported that sup-
plementing high-fat diets of mice with 2%
ethanolic extracts of H.erinaceus significantly
increased animal body weights and decreased
fat,and blood and liver triglyceride levels.
However,hot aqueous extracts had no such
effects.YUet al[54]reported that H.erinaceus
had a preventative and therapeutic effect on
ethanol-induced injury to rat gastric mucosa.
The mushroom significantly reduced hyperemia,
hemorrhage,edema and necrosis of the gastric
mucosa,reduced inflammatory cel infiltration,
promoted the recovery of the mucosal amino
hexose,and prevented rises in gastrin.XIANG
et al[55] found that H.erinaceus extracts
reduced the first defecation time and increased
the number and weight of stools in constipated
mice.H.erinaceus also reduced the ulcer index
in mice caused by ethanol and the ulcer index in
rats caused by acetic acid,but had no significant
effect on superoxide dismutase(SOD)activity
and malondialehyde levels in rat serum[8].
7 Antibacterial activity of H.erinaceus
  OKAMOTOet al[56]isolated a chlorinated
orcinol derivative with antibacterial activity from
H.erinaceus mycelium,while ZHANGet al[57]
and WONGet al[58]reported that extracts of H.
erinaceus inhibited the growth of certain
pathogenic bacteria.It is perhaps not surprising
that the fungus produces a wide variety of anti-
bacterial compounds since it is confronted with
many other microorganisms in the natural
environment[59-64].
8 Future outlook
  More than three decades have elapsed since
the development and application of H.erinaceus
Tablet, and the standards required for
introducing a new drug to the market have
changed  considerably  during  this  time.
However,since the Tablet has been used for
long periods,it is considered unnecessary in
some quarters to apply modern international
standards relating to toxicity,dose-effects,etc
(such as those applied by the United States
National Institutes of Health)to this treatment.
However,our knowledge of the bioactive
components in H.erinaceusis far from complete
since most clinical and physiological data are
based on crude extracts.Lack of information
about the active component(s)of these extracts
has not only restricted the development of new
and better products but has hindered attempts at
effective quality control of the current product.
Adopting the latest progress in H.erinaceus-
based treatments of chronic gastritis and other
diseases should provide new ideas for research
on the active components and enable this
mushroom to better serve human health.
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