CN111494435A - 猴头菇菌丝体萃取物制备用于改善中枢神经系统髓鞘化的医药组合物的用途 - Google Patents
猴头菇菌丝体萃取物制备用于改善中枢神经系统髓鞘化的医药组合物的用途 Download PDFInfo
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Abstract
本发明公开一种猴头菇菌丝体萃取物制备用于改善中枢神经系统髓鞘化的医药组合物的用途,其中萃取物包含例如猴头素A、猴头素C及/或猴头素S的活性物质。中枢神经系统的髓鞘化可由包含猴头菇活性物质的医药组合物加以改善,进而可治疗多发性硬化症、脑白质退化症、慢性神经退化症等中枢神经疾病。
Description
技术领域
本发明关于一种猴头菇菌丝体萃取物制备用于改善中枢神经系统髓鞘化的医药组合物的用途。
背景技术
脊椎动物的中枢神经系统包含两类型细胞:神经元细胞(neuron)及胶质细胞(glia),其中胶质细胞负责提供神经元细胞养分及维持微环境恒定,其细分为微胶细胞(microglia)、星状胶质细胞(astrocyte)、及寡突胶质细胞(oligodendrocyte,OLG)。其中,寡突胶质细胞(OLG)由寡突胶质前驱细胞(oligodendrocyte precursor cell,OPC)先分化为前髓鞘化寡突胶质细胞(pre-myelinating oligodendrocyte),再继续分化而成。成熟的OLG延伸其触手并缠绕神经元细胞的轴突,以形成富含脂质且多层的髓鞘(myelin),其蛋白质成分主要为髓鞘碱性蛋白(myelin basic protein,MBP)及髓鞘脂质蛋白(myelinproteolipid protein,PLP)。髓鞘的绝缘特性有助于神经讯息的传导,也保护神经元细胞。当髓鞘的结构受损或脱失时,神经传导将受阻,导致感觉、运动、认知等的缺陷。
随着年龄增加,个体将可能因为髓鞘脱失而产生持续性的轴突缺失以及神经细胞死亡而罹患神经退化性疾病。再者,OPC更新以及分化能力下降将致使再髓鞘化(re-myelination)的难度增加。中枢神经系统的疾病包括多发性硬化症(multiplesclerosis)、脑白质退化症(leukodystroph)、慢性神经退化症(chronicneurodegenerative disorders)等,都与OLG的髓鞘脱失或发生去髓鞘化有关,并与神经发炎相关。
以多发性硬化症为例,目前并未有可根治的药物,急性多发性硬化症发作时通常投予皮质类固醇来治疗,而一般的控制及治疗则对患者皮下注射干扰素及柯佩松因此,开发治疗中枢神经系统的髓鞘缺失或髓鞘损伤疾病的医药组合物或者改善中枢神经系统髓鞘化的医药组合物,进而有助于治疗或改善中枢神经系统的疾病确有迫切需求。
本案申请人鉴于现有技术中的不足,经过悉心试验与研究,并一本锲而不舍的精神,终构思出本案,能够克服现有技术的不足,以下为本案的简要说明。
发明内容
为了开发治疗中枢神经系统的髓鞘缺失或髓鞘损伤疾病的医药组合物,及改善中枢神经系统髓鞘化的医药组合物,本发明由猴头菇(Hericium erinaceus(Bull.)Pers)菌丝体获得天然及安全的萃取物,所述萃取物包含猴头素A(erinacine A)、猴头素C(erinacine C)及猴头素S(erinacine S)等活性物质。由所述萃取物制备的医药组合物能治疗中枢神经系统的髓鞘缺失或髓鞘损伤疾病,及改善中枢神经系统的髓鞘化,以有助于治疗或改善中枢神经系统的疾病,例如多发性硬化症、脑白质退化症及慢性神经退化症、脑白质损伤及脑白质发炎等。此外,本发明的猴头菇菌丝体萃取物还具有改善中枢神经系统的发炎的功效。
本发明的目的为提供一种将猴头菇菌丝体的萃取物制备用于改善个体的中枢神经系统的髓鞘化的医药组合物的用途,其中萃取物包含由猴头素A、猴头素C、猴头素S及其组合所组成的群组其中之一。
在一实施例中,萃取物系以极性溶液萃取猴头菇菌丝体而获得,且萃取物用以增进个体的寡突胶质细胞(OLG)的寡突胶质细胞转录因子1(oligodendrocytetranscription factor 1,Olig1)、寡突胶质细胞转录因子2(oligodendrocytetranscription factor 2,Olig2)、髓鞘碱性蛋白(MBP)、髓鞘脂质蛋白(PLP)的表现。在一实施例中,极性溶液为甲醇溶液、乙醇溶液或水。在一实施例中,当极性溶液分别为甲醇溶液、乙醇溶液及水时,萃取物分别为甲醇萃取物、乙醇溶液物及水萃取物。在一实施例中,寡突胶质细胞(OLG)系由寡突胶质前驱细胞(OPC)分化而成,且OPC用以分泌半乳糖脑苷酯(galactocerebroside,GC)。在一实施例中,萃取物用以促进OPC分化为OLG,俾补偿因所述中枢神经系统损伤的OLG的数量。
在一实施例中,猴头菇菌丝体系以液态发酵培养获得,且萃取物的作用浓度介于100ng/mL至1μg/mL的间。在一实施例中,猴头菇菌丝体被培养于培养基,且所述培养基包含葡萄糖、酵母抽出物、动植物来源蛋白质及其水解物、硫酸镁及黄豆粉。在一实施例中,猴头菇菌丝体在培养后经由干燥、回溶、萃取,而得到所述萃取物。
本发明还公开一种以猴头菇菌丝体萃取物、活性物质或所制备的医药组合物治疗中枢神经系统的髓鞘缺失或髓鞘损伤疾病的方法,其是将医药上有效量的萃取物、活性物质或医药组合物投予所需的个体。
因此,本发明的用于改善中枢神经系统髓鞘化或者治疗中枢神经系统的髓鞘缺失或髓鞘损伤疾病的医药组合物包括医药上有效量的猴头菇菌丝体萃取物,所述萃取物包含猴头素A、猴头素C及猴头素S等活性物质。本发明的医药组合物还包括医药上可接受的载剂、赋形剂、稀释剂或辅剂。本发明的医药组合物可以口服给药、静脉注射、皮下注射、腹腔注射、肌内注射、舌下给药等方式给予患者。
附图说明
图1为猴头素A的高效液相层析图谱。
图2为猴头素C的高效液相层析图谱。
图3为猴头素S的高效液相层析图谱。
图4(A)、(B)、(C)及(D)分别为(A)猴头菇菌丝体萃取物(HEM)、(B)猴头素A(HeA)、(C)猴头素C(HeC)以及(D)猴头素S(HeS)对OPC的细胞存活率的示意图。
图5(A)、(B)、(C)及(D)分别为(A)猴头菇菌丝体萃取物(HEM)、(B)猴头素A(HeA)、(C)猴头素C(HeC)以及(D)猴头素S(HeS)对OPC分化为OLG的Olig1、Olig2、MBP及PLP1 mRNA表现量的示意图。
图6(A)及(B)分别为猴头菇菌丝体萃取物(HEM)处理OPC而分化为(A)GC阳性OLG细胞以及(B)MBP阳性OLG细胞的示意图。
图6(C)及(D)分别为喉头素A(HeA)处理OPC而分化为(C)GC阳性OLG细胞以及(D)MBP阳性OLG细胞的示意图。
图6(E)及(F)分别为喉头素C(HeC)处理OPC而分化为(E)GC阳性OLG细胞以及(F)MBP阳性OLG细胞的示意图。
图6(G)及(H)分别为喉头素S(HeS)处理OPC而分化为(G)GC阳性OLG细胞以及(H)MBP阳性OLG细胞的示意图。
具体实施方式
本发明的上述目的及优点在参阅以下详细说明及附随图示的后对那些所属技术领域中具有通常知识者将变得更立即地显而易见。
本发明使用猴头菇,其主要分布于纬度较高的温带地区,其子实体的多醣类具有利五脏、助消化、改善消化不良、改善身体虚弱、治疗胃溃疡、胃炎、胃痛及胃胀的功效,因此猴头菇可作为食、药两用菇类。
一、实验方法:
1.猴头菇菌丝体的液态发酵培养
本发明实施例的猴头菇为来自财团法人食品工业发展研究所生物资源保存及研究中心编号BCRC 35669的品种。然而,适用于本发明的猴头菇品种不在此限。
首先,将猴头菇菌丝体(BCRC编号:35669)无菌接种于马铃薯葡萄糖洋菜(potatodextrose agar,PDA)平板培养基上,于25℃培养7天。再以无菌技术刮取PDA平板培养基上的猴头菇菌丝体,接种于装有培养基(含2.0重量%的葡萄糖、0.1重量%的酵母抽出物、0.1重量%的动植物来源蛋白及其水解物、0.001重量%的硫酸镁、0.1重量%的黄豆粉,并加水至100重量%)的烧瓶内,在26℃、pH 5.0、转速120rpm震荡培养箱内震荡培养5天。的后,将烧瓶内的猴头菇菌丝体无菌接种至含上述培养基的发酵槽内,在24℃~30℃、槽压0.5~1.0公斤/平方公分、pH 5.0下、10-150rpm搅拌速度或不搅拌(air lift)情况,以0.5-1.0VVM通气速率通入空气,培养7~10天,获得猴头菇菌丝体的液态培养发酵液。离心去除上清液,留下的固形物即为猴头菇菌丝体。将此固形物冷冻干燥获得猴头菇菌丝体粉末,以利于冷冻保存。
2.猴头菇菌丝体萃取物的制备
以极性溶液萃取猴头菇菌丝体粉末数分钟(包含但不限于浸泡、搅拌、震荡或超音波萃取法),再以减压浓缩法或冷冻干燥法进行干燥,获得猴头菇菌丝体的萃取物。极性溶液包括但不限于甲醇溶液、乙醇溶液或水。当个别使用上述溶液时,分别获得猴头菇菌丝体的甲醇萃取物、乙醇萃取物或水萃取物。甲醇溶液为甲醇与水混合的溶液(例如1%(v/v)以上、未满100%(v/v))或者“纯”甲醇,乙醇溶液为乙醇与水混合的溶液(例如1%(v/v)以上、未满100%(v/v))或者“纯”乙醇。
本实验系以95%(v/v)乙醇溶液进行萃取。将猴头菇菌丝体粉末加入其25倍重量的95%(v/v)乙醇溶液,进行第一次超音波震荡萃取1小时,将悬浮液离心获得第一上清液。接着,将上清液以85%(v/v)乙醇溶液进行第二次超音波震荡萃取1小时,将悬浮液离心获得第二上清液。将第二上清液减压浓缩,获得膏状的猴头菇菌丝体萃取物(简称萃取物)。
3.猴头菇菌丝体萃取物的活性成分分析
将萃取物经由水-乙酸乙酯(1:1,v/v)的液液分配萃取,获得乙酸乙酯层,再将所述乙酸乙酯层以硅胶及LH-20硅胶管柱色层分析。在高效液相层析(HPLC)中,以5C18-AR-II管柱在40℃下,以起始的60%乙腈冲提,在20分钟内逐渐提升至65%乙腈,流速1ml/min,波长为340nm。如图1所示,猴头素A(erinacine A,符号A,MW:432.557g/mol)出现于7.3分钟。在HPLC中,以5C18-AR-II管柱在40℃下,以起始的60%乙腈冲提,在20分钟内逐渐提升至65%乙腈,流速1ml/min,波长为210nm。如图2所示,猴头素C(erinacine C,符号C,MW:434.573g/mol)出现于10.4分钟。在HPLC中,以5C18-AR-II管柱在40℃下,以起始的60%乙腈冲提,在20分钟内逐渐提升至65%乙腈,流速1ml/min,波长为290nm。如图3所示,猴头素S(erinacine S,符号S,MW:430.541g/mol)出现于14.5分钟。猴头素A、C及S的化学结构式如下所示。
据此,在20公吨发酵槽培养的猴头菇菌丝体经干燥可得约120公斤的猴头菇菌丝体粉末。经萃取的猴头菇菌丝体萃取物含有猴头素A、C、S等活性物质。含有猴头素A、C、S的猴头菇菌丝体、粉末、萃取物可依需要制备为各式医药组合物或保健食品的剂型。
4.寡突胶质前驱细胞(OPC)分化成寡突胶质细胞(OLG)的建立及分析
由怀孕13.5~14.5天的Sprague-Dawley(SD)母鼠的胚胎分离其大脑皮质层,将胚胎的大脑皮质层分散后通过40μm孔径过滤膜,将皮质层培养于未经过聚离胺酸(poly-D-lysine,PDL)处理的细胞培养皿5~7天,以形成球体状的神经干细胞。以Accutase细胞消化酶将神经干细胞由细胞培养皿上分离下来,将细胞重新悬浮于生长培养液(含2%的B-27TM添加物(Gibco)、1%的N-2TM添加物(Gibco)、10ng/ml纤维母细胞生长因子2(FGF2)、10ng/ml表皮生长因子(EGF)及10ng/ml血小板衍生生长因子-AA配体(PDGF-AA ligand)的DMEM/F12培养基)并种植于经过PDL处理的细胞培养皿。2天后将生长培养液更换为分化培养液(含4mM的L-麸酰胺酸(L-glutamine)、1mM丙酮酸钠(sodium pyruvate)、0.1%牛血清白蛋白(BSA)、50mg/ml原运铁蛋白(apotransferrin)、5mg/ml胰岛素、30nM亚硒酸钠、10nM生物素、10nM氢皮质酮(hydrocortisone)、15nM T3、10ng/ml毛状神经营养因子(ciliaryneurotrophic factor,CNTF)及5mg/ml N-乙酰-L半胱胺酸(N-acetyl-L-cysteine,NAC)的DMEM培养基),并培养2天,再依实验需求以猴头菇菌丝体萃取物(简称HEM)、猴头素A(简称HeA)、猴头素C(简称HeC)及猴头素S(简称HeS)处理。
5.寡突胶质前驱细胞(OPC)分化成寡突胶质细胞(OLG)的细胞存活率
此试验是评估HEM、HeA、HeC、HeS是否影响OPC的存活率。首先,将2×104个OPC细胞种植于24孔培养盘并培养2天,再以不同浓度的萃取物或猴头素处理24及48小时。加入0.5mg/ml的3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT)避光作用4小时,以二甲基亚砜(DMSO)溶解蓝紫色结晶formazan,再以酵素免疫分析测读仪(TECAN SunriseELISA Reader)测量波长595nm的吸光值,计算细胞存活率。
6.OLG的髓鞘化能力
此试验是以定量即时聚合酶链反应(quantitative real-time polymerasechain reaction,Q-PCR)测定经处理后的细胞的特定基因表现量,以分析OLG的髓鞘化能力。首先,将经过猴头菇萃取物处理后的OLG的RNA(1ug/样本)以莫洛尼氏鼠类白血肿瘤病毒反转录酶(M-MLV reverse transcriptase)将其转录成cDNA。将cDNA、MasterMixes及大鼠寡突胶质细胞转录因子1(Olig1)、寡突胶质细胞转录因子2(Olig2)、髓鞘碱性蛋白(MBP)或髓鞘脂质蛋白(PLP)引子混合(参见表1),测定相对mRNA表现量,并以大鼠GAPDH基因为控制组基因。以StepOne软体2.12版(Applied Biosystems)分析实验结果。
表1、引子序列表
7.西方墨点法(Western Blot)
此试验是以习用的十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)及西方墨点法分析细胞的蛋白质表现量。简而言的,细胞蛋白质经过SDS-PAGE后转渍至硝化纤维膜上,加入一次抗体于低温作用15小时以上。以TBST缓冲液清洗硝化纤维膜,再加入二次抗体于室温作用1小时。以TBST缓冲液清洗硝化纤维膜,再以ECL进行冷光呈色,于底片显影。
8.免疫萤光染色
以4%三聚甲醛(paraformaldehyde)固定经处理的细胞玻片15分钟,再以0.1%Triton X100 PBS作用15分钟。以PBS清洗3次,再加入含有1%马血清的抗MBP的抗体(NB1018,Calbiochem)或抗半乳糖脑苷酯(GC)的抗体(MAB342,Millipore),于4℃隔夜作用。以PBS清洗3次,加入接有生物素的二次抗体,于室温作用1小时。以PBS清洗3次,加入含有avidin-Cy3的三次抗体,室温作用45分钟。以DAPI(1μg/ml)反应1分钟,最后以90%甘油封片,于显微镜(FV1000,Japan)观察结果。
9.动物实验模式的建立
以震动式活组织切片机(MicroslicerTM DTK-1000vibratory tissue slicer)将出生7天的SD大鼠仔鼠的小脑切成厚度为300μm的薄片,置于插入式细胞培养皿(0.4μmcell culture insert,Millipore),以小脑组织切片培养液(Cerebellarslice culture medium,含50%的含厄尔盐(Earle’s salt)的最低必需培养基(MEM)、35%厄尔平衡盐溶液、15%热失活的马血清及1%的GlutaMAXTM补充剂)培养3天。以不同浓度的猴头菇萃取物或猴头素处理切片11天,于共同培养的第14天时使用4%三聚甲醛固定2小时,再以1%Triton-X100 PBS作用2天。以免疫萤光法进行抗髓鞘碱性蛋白的小鼠单株抗体(anti-myelin basic protein mouse(anti-MBP)mAb,NE1018,Calbiochem)及抗神经纤维丝H的抗体(anti-neurofilament H antibody,NF200,AB5539,Millipore)的双萤光染色,在显微镜(FV1000,Japan)下观察结果。
10.统计分析
实验数据以“平均值±标准误”表示,以t-test分析组间差异,p<0.05为具有统计学上显著差异。
二、实验结果:
1.HEM、HeA、HeC及HeS对OPC的细胞存活率
请参阅图4(A)、(B)、(C)及(D),其分别为(A)猴头菇菌丝体萃取物(HEM)、(B)猴头素A(HeA)、(C)猴头素C(HeC)以及(D)猴头素S(HeS)对OPC的细胞存活率的示意图。图4(A)至(D)的对照组为未加萃取物或活性物质处理的试验。在图4(A)至(D)中,以10ng/ml~100μg/ml的HEM处理OPC细胞24~48小时,并不会对OPC细胞产生毒性(图4(A));而0.001ng/ml~10ng/ml的HeA、HeC及HeS处理OPC细胞24~48小时亦不会对OPC细胞产生毒性(图4(B)、(C)及(D))。因此,可证明在适当浓度下,猴头菇菌丝体萃取物(HEM)、活性物质(HeA、HeC及HeS)均不影响OPC的细胞存活率,对OPC是安全、无毒性的。
2.HEM、HeA、HeC及HeS对OPC分化为OLG的影响及基因表现
请参阅图5(A)、(B)、(C)及(D),其分别为(A)猴头菇菌丝体萃取物(HEM)、(B)猴头素A(HeA)、(C)猴头素C(HeC)以及(D)猴头素S(HeS)对OPC分化为OLG的Olig1、Olig2、MBP及PLP1 mRNA表现量的示意图。图5(A)至(D)的对照组为未以萃取物或活性物质处理的试验。在图5(A)中,100ng/ml~1μg/ml的HEM增加了OLG细胞的Olig2 mRNA表现量(小图(A)-2),而成熟的OLG细胞的MBP及PLP1 mRNA表现量亦增加(小图(A)-3及(A)-4)。此外,经100ng/ml及1μg/ml的HEM处理的OPC细胞,分化后的OLG细胞数目高于控制组(结果未示出)。
在图5(B)中,0.001ng/ml~10μg/ml的HeA同样增加了OLG细胞的Olig2 mRNA表现量(小图(B)-2),HeA亦促进OLG细胞的MBP及PLP1 mRNA表现量增加(小图(B)-3及(B)-4)。
在图5(C)中,不同浓度的HeC增加OLG细胞的Olig1、Olig2、MBP及PLP1 mRNA表现量,例如0.01ng/ml~10ng/ml的HeC增加OLG细胞的Olig1 mRNA表现量(小图(C)-1),0.1ng/ml~10ng/ml的HeC增加OLG细胞的Olig2 mRNA表现量(小图(C)-2),0.01ng/ml的HeC大幅度地增加OLG细胞的MBP mRNA表现量(小图(C)-3),HeC对OLG细胞的PLP1 mRNA表现量并无显著差异(小图(C)-4)。
在图5(D)中,0.01ng./ml的HeS可大幅度地增加OLG细胞的Olig1、MBP、PLP mRNA表现量(小图(D)-1、(D)-3及(D)-4),0.001ng/ml~0.1ng/ml的HeS可增加OLG细胞的Olig2mRNA表现量(小图(D)-2)。0.01ng/ml的HeS可促进OLG细胞的MBP及PLP蛋白质的表现量(西方墨点法结果未示出)。
请参阅图6(A)至(H),免疫萤光染色实验结果显示,萃取物(HEM)及活性物质(HeA、HeC及HeS)均能促进OPC分化为带有GC阳性的OLG(图6(A)、(C)、(E)及(G))以及带有MBP阳性的OLG(图6(B)、(D)、(F)及(H))。定量结果亦显示,HeS促进OPC分化为带有GC阳性的OLG以及带有MBP阳性的OLG(图6(G)及(H))的能力较HeA(图6(C)及(D))或HeC(图6(E)及(F))还要好。
综上所述,本发明的猴头菇菌丝体萃取物及其活性物质(HeA、HeC及HeS)对寡突胶质前驱细胞(OPC)是安全、无毒性的,可促进OPC分化为寡突胶质细胞(OLG),并促进OLG缠绕轴突的髓鞘化过程的寡突胶质细胞转录因子1(Olig1)、寡突胶质细胞转录因子2(Olig2)、髓鞘碱性蛋白(MBP)、髓鞘脂质蛋白(PLP)的mRNA表现量及蛋白质表现量,并使OLG为成为带有半乳糖脑苷酯(GC)阳性及带有MBP阳性的OLG。因此,本发明的猴头菇菌丝体萃取物及其所含的猴头素A、C及S可被用于制备改善个体中枢神经系统髓鞘化或者治疗髓鞘缺失或髓鞘损伤的疾病的医药组合物的用途。
本发明实属难能的创新发明,深具产业价值,援依法提出申请。此外,本发明可以由所属技术领域中具有通常知识者做任何修改,但不脱离如所附权利要求书所要保护的范围。
符号说明
A 猴头素A
C 猴头素C
S 猴头素S
<110> 葡萄王生技股份有限公司
<120> 猴头菇菌丝体萃取物制备用于改善中枢神经系统髓鞘化的医药组合物的用途
<160> 10
<170> PatentIn version 3.5
<210> 1
<211> 20
<212> DNA
<213> Olig1-Forward
<400> 1
GAGGGGCCTC TTTCCTTGTC 20
<210> 2
<211> 20
<212> DNA
<213> Olig1-Reverse
<400> 1
ACCGAGCTTC ACAAGCCTAC 20
<210> 3
<211> 20
<212> DNA
<213> Olig2-Forward
<400> 1
GCTTAACAGA GACCCGAGCC 20
<210> 4
<211> 20
<212> DNA
<213> Olig2-Reverse
<400> 1
GTGGCGATCT TGGAGAGCTT 20
<210> 5
<211> 20
<212> DNA
<213> MBP-Forward
<400> 1
GTGGGGGTAA GAGAAACGCA 20
<210> 6
<211> 20
<212> DNA
<213> MBP-Reverse
<400> 1
CGAACACTCC TGTGGAACGA 20
<210> 7
<211> 20
<212> DNA
<213> PLP-Forward
<400> 1
GGCGACTACA AGACCACCAT 20
<210> 8
<211> 20
<212> DNA
<213> PLP-Reverse
<400> 1
AATGACACAC CCGCTCCAAA 20
<210> 9
<211> 18
<212> DNA
<213> GAPDH-Forward
<400> 1
TCTACCCACG GCAAGTTC 18
<210> 10
<211> 18
<212> DNA
<213> GAPDH-Reverse
<400> 1
GATGTTAGCG GGATCTCG 18
Claims (10)
1.一种将猴头菇菌丝体的萃取物制备用于改善个体的中枢神经系统的髓鞘化的医药组合物的用途,其中所述萃取物包含由猴头素A、猴头素C、猴头素S及其组合所组成的群组其中之一。
2.根据权利要求2所述的用途,其中所述萃取物系以极性溶液萃取所述猴头菇菌丝体而获得,且所述萃取物用以增进所述个体的寡突胶质细胞(oligodendrocyte,OLG)的寡突胶质细胞转录因子1(Olig1)、寡突胶质细胞转录因子2(Olig2)、髓鞘碱性蛋白(myelinbasic protein,MBP)、髓鞘脂质蛋白(myelin proteolipid protein,PLP)的表现。
3.根据权利要求2所述的用途,其中所述极性溶液为甲醇溶液、乙醇溶液或水。
4.根据权利要求3所述的用途,其中当所述极性溶液为所述甲醇溶液时,所述萃取物为甲醇萃取物;当所述极性溶液为所述乙醇溶液时,所述萃取物为乙醇萃取物;且当所述极性溶液为水时,所述萃取物为水萃取物。
5.根据权利要求2所述的用途,其中所述寡突胶质细胞(OLG)系由寡突胶质前驱细胞(oligodendrocyte precursor cell,OPC)分化而成,且所述寡突胶质前驱细胞(OPC)用以分泌半乳糖脑苷酯(galactocerebroside,GC)。
6.根据权利要求5所述的用途,其中所述萃取物用以促进所述寡突胶质前驱细胞(OPC)分化为所述寡突胶质细胞(OLG),俾补偿因所述中枢神经系统损伤的寡突胶质细胞(OLG)的数量。
7.根据权利要求1所述的用途,其中所述猴头菇菌丝体系以液态发酵培养获得,且所述萃取物的作用浓度介于10ng/mL至100μg/mL的间。
8.根据权利要求1所述的用途,其中所述萃取物或所述医药组合物更用于治疗所述个体的中枢神经系统的髓鞘缺失或髓鞘损伤的疾病。
9.根据权利要求1所述的用途,其中所述猴头菇菌丝体被培养于培养基,且所述培养基包含葡萄糖、酵母抽出物、动植物来源蛋白质及其水解物、硫酸镁及黄豆粉。
10.根据权利要求1所述的用途,其中所述猴头菇菌丝体在培养后经由干燥、回溶、萃取,而得到所述萃取物。
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