CN109833358A - 刺梨萃取物用于制备细胞回春组合物的用途 - Google Patents
刺梨萃取物用于制备细胞回春组合物的用途 Download PDFInfo
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Abstract
本发明是关于一种刺梨萃取物的保健用途,特别是关于一种刺梨萃取物用于制备细胞回春组合物的组合物的用途。该刺梨萃取物是以水、醇类、或醇水混合物为溶剂对刺梨进行萃取而制得,其能促进基因修复、减少氧化或发炎造成的细胞损伤及维持基因、蛋白质、及粒线体的正常运作,并且能刺激端粒酶反应与减少端粒因化学药物或紫外线照射而受损,因此促进细胞回春。
Description
技术领域
本发明是关于一种刺梨萃取物的保健用途,特别是关于一种刺梨萃取物用于制备细胞回春组合物的组合物的用途。
背景技术
随着人口平均年龄的延长,拥有健康而高质量的老年生活成为大众关注的焦点之一,关于老化的科学研究也越发受重视。个体老化的原因众多,在分子及细胞层次,可能的内部机制包括染色体末端的端粒(telomere)缩短、基因突变、蛋白质合成效率不良、粒线体功能下降、细胞形态变异等。此外,细胞周围环境中由物理或化学因素产生的自由基(如活性氧物质)会损害细胞的染色体脱氧核醣核酸(DNA)、蛋白质、及脂质生物膜,而个体为因应此类细胞损伤或微生物入侵而启动的发炎反应一旦发展为慢性发炎更会加剧细胞损伤,因此加速细胞及个体老化。
对抗老化的方法包括通过饮食获取天然抗氧化剂以提升个体清除自由基的能力,以及藉由抗发炎药抑制体内的慢性发炎。鉴于上述复杂的老化成因,针对单一目标而设计的抗老化方法显然成效不彰。目前新兴的干细胞疗法虽然是极具抗老化潜力,然其尚处于发展阶段,且治疗费用高昂。因此,开发一种简单的新颖组合物,以复合方式维持个体或细胞处于年轻状态,实有其必要。
发明内容
缘此,本发明的一目的在提供一种刺梨(Rosa roxburghii fruit)萃取物用于制备细胞回春组合物的用途,其中该刺梨萃取物是以一溶剂萃取一刺梨而获得。
在本发明的一实施例中,该溶剂为水、醇类、或醇水混合物,该溶剂与刺梨的液固比为5~20∶1~5,且该萃取是在50℃~100℃进行。
在本发明的一实施例中,该刺梨萃取物是为一刺梨的水萃取物,其浓度为至少0.5mg/mL。
在本发明的一实施例中,该刺梨萃取物促进一端粒酶的合成,以及增强端粒酶反转录酶(telomerase reverse transcriptase,TERT)、端粒酶核醣核酸组分(telomeraseRNA component,TERC)、或其组合的基因表现。
在本发明的一实施例中,该刺梨萃取物减少染色体端粒因化学药物或紫外线照射而长度缩短。
在本发明的一实施例中,该刺梨萃取物促进基因修复,以及增强一DNA修复蛋白的基因表现,该DNA修复蛋白是选自于由MPG(N-methylpurine DNA glycosylase,N-甲基嘌呤DNA醣基化酶)、ERCC6(excision repair cross complementing 6,核苷酸剪切修复交叉互补蛋白6)、XRCC5(X-ray repair cross complementing 5,X射线修复交叉互补蛋白5)、及其任意组合所组成的群组。
在本发明的一实施例中,该刺梨萃取物促进一伴随蛋白T复合体(chaperonincontaining TCP1 complex,CCT)的合成,以及增强该伴随蛋白T复合体的一蛋白次单元的基因表现,该蛋白次单元是选自于由CCT2、CCT5、CCT6A、CCT7、CCT8、及其任意组合所组成的群组。
在本发明的一实施例中,该刺梨萃取物提升粒线体活性,以及抑制一聚二磷酸腺苷核糖聚合酶(亦称聚ADP核糖聚合酶,poly(ADP-ribose)polymerase,PARP)的基因表现,该PARP是选自于由PARP1、PARP3、PARP4、PARP8、PARP11、及其任意组合所组成的群组。
本发明基于基因表现分析结果,揭示刺梨萃取物能同时减少氧化压力(oxidativestress)或发炎造成的细胞损伤以及维持基因、蛋白质、与粒线体的正常运作,并且能刺激端粒酶反应与减少端粒因化学药物或紫外线照射而受损,因此促进细胞回春。因此,本发明提供刺梨萃取物用于制备细胞回春组合物的用途,该组合物可为粉末状、颗粒状、液状、胶状或膏状,且可制成食品、饮品、药品、试剂或营养补充剂,藉由口服、皮肤涂抹等方式给予一个体。
以下将配合图式进一步说明本发明的实施方式,下述所列举的实施例是用以阐明本发明的发明特点及应用,而非以限定本发明的范围,任何熟习此技艺者,在不脱离本发明的精神和范围内,当可做些许更动与润饰,因此本发明的保护范围当视后附的申请专利范围所界定者为准。
附图说明
图1显示受脂多醣(lipopolysaccharide,LPS)刺激的THP-1细胞在有或无刺梨萃取物处理24小时后相对于控制组细胞的超氧化物歧化酶2(superoxide dismutase 2,SOD2)基因的相对表现量;
图2显示受脂多醣(LPS)刺激的THP-1细胞在有或无刺梨萃取物处理6小时后相对于控制组细胞的CC趋化因子配体3(C-C motif chemokine ligand 3,CCL3)基因的相对表现量;
图3显示受脂多醣(LPS)刺激的THP-1细胞在有或无刺梨萃取物处理6小时后相对于控制组细胞的介白素-1受体拮抗因子(interleukin-1 receptor antagonist,IL-1RA)与介白素-10(interleukin-10,IL-10)基因的相对表现量;
图4显示受脂多醣(LPS)刺激的THP-1细胞在有或无刺梨萃取物处理6小时后相对于控制组细胞的MPG、ERCC6、及XRCC5基因的相对表现量;
图5显示经刺梨萃取物处理6小时或24小时的THP-1细胞相对于控制组细胞的CCT2、CCT5、CCT6A、CCT7、及CCT8基因的相对表现量;
图6显示经刺梨萃取物处理6小时或24小时的THP-1细胞相对于控制组细胞的PARP1、PARP3、PARP4、PARP8、及PARP11基因的相对表现量;
图7显示经刺梨萃取物处理6小时的THP-1细胞与控制组细胞的TERT与TERC基因的相对表现量;
图8显示刺梨水萃取物对化学药物所致皮肤细胞的端粒缩短的抑制作用;
图9显示刺梨水萃取物对紫外线照射所致皮肤细胞的端粒缩短的抑制作用。
具体实施方式
本发明提供一种刺梨萃取物用于制备细胞回春组合物的用途。本发明的刺梨萃取物是以一溶剂萃取一刺梨而获得,其中,该溶剂为水、醇类、或醇水混合物,该溶剂与该刺梨的液固比为5~20∶1~5,且该萃取是在50℃~100℃进行。基于基因表现量分析技术,该刺梨萃取物经证实能促进抗氧化相关基因、抗发炎细胞激素基因、DNA修复相关蛋白基因、伴随蛋白T复合体(CCT)的蛋白次单元基因、及端粒酶反应相关基因的表现,并且抑制发炎反应相关基因及粒线体机能失调关联基因的表现,以及减少染色体端粒因化学药物或紫外线照射而长度缩短。
定义
本文中所使用数值为近似值,所有实验数据皆表示在20%的范围内,较佳为在10%的范围内,最佳为在5%的范围内。
本文中所谓「细胞回春」是指逆转细胞老化现象发生的过程,其可藉由多种生物指标判断,例如促进参与细胞DNA修复、端粒酶反应、蛋白质正常作用的基因表现,促进与粒线体活性相关的蛋白质或RNA的基因表现,及促进染色体端粒延长。
材料与方法
细胞培养
以下实施例使用购自美国典型培养物保存中心(American Type CultureCollection,ATCC)的人类单核细胞株(human monocytic cell line)THP-1(ATCC TIB202)及购自食品工业发展研究所生物资源保存及研究中心(Bioresource Collection andResearch Center,BCRC)的人类皮肤纤维母细胞(human skin fibroblast)CCD-966SK(BCRC 60153)。THP-1细胞在37℃、5%二氧化碳的条件下培养于添加10%胎牛血清(fetalbovine serum,FBS)与1%青霉素-链霉素的RPMI培养基(RPMI medium 1640;Gibco),以下称RPMI细胞培养基。CCD-966SK细胞在37℃、5%二氧化碳的条件下培养于添加10%FBS及1%青霉素-链霉素的最低基础培养基(Minimum Essential Medium(MEM);Gibco),以下称MEM细胞培养基。
基因体芯片分析
利用人类基因体芯片(由华联生物科技股份有限公司制造)测定细胞的基因体表现变化,其步骤简述如下。依据厂商使用说明,利用RNA萃取套组(RNA Extraction Kit;Geneaid)自THP-1细胞分离出RNA,以其为模板于37℃下以带有T7启动子(T7promoter)序列的胸腺嘧啶脱氧寡核苷酸引物(oligo dT primer)进行反转录以合成第一股互补脱氧核醣核酸(cDNA),再以DNA聚合酶及RNA酶H(RNase H)合成双股cDNA。经纯化后,以该双股cDNA为模板,在添加氨基烯丙基尿苷三磷酸(amino allyl UTP,aaUTP)的环境利用RNA扩增套组(Amino Allyl MessageAmpTM aRNA Amplification kit;Invitrogen)进行试管内转录(invitro transcription)以合成氨基烯丙基修饰的RNA(简称aRNA)。经纯化后的aRNA可与如Cy5的氨基反应性荧光染剂(Cy5 NHS ester;AAT Bioquest)结合而生成染剂标记的RNA。藉由透析移除未结合的染剂及纯化得经染剂标记的RNA后,将其添加至载有复数特定基因探针的人类基因体芯片,以杂合套组(Hybridization kit;Phalanx)进行杂合反应。该复数特定基因所编码的蛋白质包含抗氧化相关的SOD2、发炎反应相关的CCL3、抗发炎细胞激素IL-1RA与IL-10、DNA修复相关蛋白如MPG、ERCC6、XRCC5、伴随蛋白T复合体(CCT)的多种蛋白次单元如CCT2、CCT5、CCT6A、CCT7、及CCT8、以及与粒线体机能失调有关的多种聚ADP核糖聚合酶(PARP),包括PARP1、PARP3、PARP4、PARP8、及PARP11。该基因体芯片于杂合反应后是利用微数组扫描仪(Agilent microarray scanner)侦测杂合的荧光讯号。初始数据经标准化后以log2对数值表示基因的相对表现量。统计分析系使用Excel软件中的STDEV函数计算各基因相对表现量的标准偏差,并以单尾学生T检验(TTEST)计算统计上差异。
基因表现量分析
基于定量聚合酶链锁反应(quantitative polymerase chain reaction,简称qPCR)测定细胞中参与端粒酶反应的端粒酶反转录酶(TERT)及端粒酶RNA组分(TERC)的基因表现量,其步骤简述如下。依据厂商使用说明,利用RNA萃取套组(RNA Extraction Kit;Geneaid)自细胞分离出RNA,于37℃下以反转录酶III ReverseTranscriptase(Invitrogen)将2000ng RNA反转录为cDNA。其次,利用qPCR套组(KAPA CYBRFAST qPCR Kit(2X);KAPA Biosystems)以及TERT、TERC等目标基因与作为内部对照的甘油醛3-磷酸脱氢酶(Glyceraldehyde 3-phosphate dehydrogenase,GAPDH)基因的引物对(表1)在PCR反应仪(Step One Plus Real-Time PCR system;Applied Biosystems)对前述cDNA进行qPCR,以取得解链曲线(melting curve)。
表1
最终,使用2-ΔΔCT方法测定目标基因的相对表现量。该方法以GAPDH基因的循环阈值(CT)作为内部对照的参考基因的循环阈值,按照以下公式计算相对倍数变化:
ΔCT=实验组或控制组的目标基因的CT-内部对照的CT
ΔΔCT=实验组的ΔCT-控制组的ΔCT
倍数变化=2-ΔΔCt平均值
统计分析系使用Excel软件中的STDEV函数计算各基因相对表现量的标准偏差,并以单尾学生T检验(TTEST)计算统计上差异。
端粒长度测定
端粒长度是基于qPCR技术而测定。首先,由细胞萃取得基因体DNA样品。其次,利用qPCR套组(KAPA CYBR FAST qPCR Kit(2X);KAPA Biosystems)以及端粒与36B4基因(单拷贝数基因)的引物对(表2)在PCR反应仪对该基因体DNA样品(20ng)进行qPCR,以获得解链曲线。同时,制备端粒(自60pg稀释10至106倍)与36B4基因(自200pg稀释10至106倍)的连续稀释标准品,以下列反应条件进行qPCR以获得该二者的标准曲线(Ct/kb):10分钟变性阶段(95℃),其后为40个循环的15秒变性阶段(95℃)与1分钟黏合阶段。作为标准品的端粒是具有14重复的TTAGGG的寡核苷酸(SEQ ID NO:7);作为标准品的36B4基因具有SEQ ID NO:8的核苷酸序列。最终,由前述标准曲线及基因体DNA样品的端粒与36B4基因的循环阈值计算基因体DNA样品中端粒的平均长度。
表2
实施例1
刺梨萃取物的制备
首先,洗净及干燥包含果皮与刺的完整刺梨果实,使用均质机将其粗碎。其次,以水、醇类、或醇水混合物为溶剂对刺梨果实均质物进行萃取。该溶剂与该刺梨果实均质物混合的液固比为5~20∶1~5。萃取温度为介于50℃至100℃,较佳为70℃至95℃。本实施例中萃取时间为0.5至3小时。
经上述萃取步骤所得刺梨萃取物冷却至室温后,可以400目(mesh)的滤网过滤,以移除残余固体物。该过滤后的刺梨萃取物可进一步在45℃~70℃进行减压浓缩而获得一浓缩产物。为获得固态的刺梨萃取物,可将前述经减压浓缩的刺梨萃取物以喷雾干燥方式去除溶剂,因此获得刺梨萃取物粉末。前述喷雾干燥步骤前,刺梨萃取物可选择性地与麦芽糊精依5~20∶1~5的重量比(w/w)混合。
实施例2
刺梨萃取物减少细胞损伤及促进DNA修复与细胞回春
本实施例以人类基因体芯片分析人类单核细胞株THP-1经刺梨的水萃取物处理后,其基因体表现的变化。刺梨的醇萃取物或醇水萃取物亦做相同分析(数据未显示)。首先,将THP-1细胞依1.5×105个细胞/孔接种于含有2mL RPMI细胞培养基的6孔盘的各孔,在37℃下培养24小时后,移除该细胞培养基并以PBS溶液清洗细胞。其后,将500μL的1mg/mL刺梨水萃取物与500μL不含FBS的RPMI细胞培养基添加至各孔细胞(实验组),或者仅以500μL不含FBS的RPMI细胞培养基处理细胞以作为控制组。实验组细胞在有或无10μg/mL脂多醣刺激的情况下于37℃培养6或24小时后用于基因表现分析,其指定基因的相对表现量是相对于控制组细胞的相同基因在同等培养时间后的表现量的倍数取log2值。
图1显示受脂多醣刺激的THP-1细胞在有或无刺梨水萃取物处理24小时后相对于控制组细胞的SOD2基因的相对表现量。依据图1,相比单纯接受脂多醣刺激的THP-1细胞,同时对细胞施予刺梨萃取物明显提升SOD2的基因表现,此结果说明刺梨萃取物能提高细胞移除活性氧物质的能力,因此保护细胞免于氧化压力的伤害,例如来自细胞本身及环境的自由基所造成的氧化伤害。
图2显示受脂多醣刺激的THP-1细胞在有或无刺梨水萃取物处理6小时后相对于控制组细胞的CCL3基因的相对表现量。图3显示受脂多醣刺激的THP-1细胞在有或无刺梨水萃取物处理6小时后相对于控制组细胞的IL-1RA与IL-10基因的相对表现量。依据图2至图3,相比单纯接受脂多醣刺激的THP-1细胞,同时对细胞施予刺梨萃取物明显抑制与发炎反应相关的CCL3基因的表现,并且提升抗发炎细胞激素IL-1RA与IL-10的基因表现,此结果说明刺梨萃取物能抑制免疫细胞诱使发炎反应发生,因此减少个体细胞因过度发炎反应而受损。
图4显示受脂多醣刺激的THP-1细胞在有或无刺梨水萃取物处理6小时后相对于控制组细胞的MPG、ERCC6、及XRCC5基因的相对表现量。依据图4,相比单纯接受脂多醣刺激的THP-1细胞,同时对细胞施予刺梨萃取物明显增强前述三种DNA修复蛋白的基因表现,此结果说明刺梨萃取物能提升细胞对受损DNA或基因的修复能力,故可维持基因的正常运作。
图5显示经刺梨水萃取物处理6小时或24小时的THP-1细胞相对于控制组细胞的CCT2、CCT5、CCT6A、CCT7、及CCT8基因的相对表现量。依据图5,刺梨萃取物的处理提升THP-1细胞的伴随蛋白T复合体次单元的基因表现,包含CCT2、CCT5、CCT6A、CCT7、及CCT8基因。此结果说明刺梨萃取物能增加协助蛋白质折迭的伴随蛋白T复合体的合成,因此有益于细胞内蛋白质具有正常结构及发挥正常功能。
图6显示经刺梨水萃取物处理6小时或24小时的THP-1细胞相对于控制组细胞的PARP1、PARP3、PARP4、PARP8、及PARP11基因的相对表现量。依据图6,刺梨萃取物的处理会抑制THP-1细胞中多种聚ADP核糖聚合酶(PARP)的基因表现。鉴于先前研究指出该种酵素活性的抑制可改善粒线体活性,此结果显示刺梨萃取物能增加粒线体活性,因而改善细胞的能量产生。基于图1-6的实验结果,刺梨萃取物具有使细胞回春的功效。
实施例3
刺梨萃取物增强端粒酶反应相关基因的表现
先前研究揭露提高细胞中的端粒酶活性可促进细胞生长。为探讨刺梨萃取物对端粒酶反应相关基因表现的影响,以qPCR测定人类单核细胞株THP-1经刺梨的水萃取物处理后,其端粒酶反转录酶(TERT)及端粒酶RNA组分(TERC)的基因表现变化。首先,将THP-1细胞依1.5×105个细胞/孔接种于含有2mL RPMI细胞培养基的6孔盘的各孔,在37℃下培养24小时后,移除该细胞培养基并以PBS溶液清洗细胞。其后,将500μL的2mg/mL刺梨水萃取物与500μL不含FBS的RPMI细胞培养基添加至各孔细胞(实验组),或者仅以500μL不含FBS的RPMI细胞培养基处理细胞以作为控制组。前述二组细胞于37℃培养6小时后用于qPCR分析。
图7显示经刺梨水萃取物处理6小时的THP-1细胞与控制组细胞的TERT与TERC基因的相对表现量,图中纵坐标的相对表现量表示相对于控制组细胞中相同基因的RNA表现量的倍数。依据图7,对THP-1细胞施予刺梨萃取物分别提高TERT与TERC基因的表现量达2倍及1.5倍。此结果说明刺梨萃取物能增加细胞中的端粒酶反应及延长端粒,因此具备延长细胞生命或推迟老化的效果。
实施例4
刺梨萃取物抑制染色体端粒长度的缩短
4.1对抗化学药物所致端粒缩短
本实施例探讨刺梨的水萃取物对人类皮肤纤维母细胞CCD-966SK的染色体端粒的保护作用。首先,CCD-966SK细胞依1.5×105个细胞/盘接种于各含有2mL MEM细胞培养基的三个35mm培养盘,在37℃下培养隔夜后,自各培养盘取半数细胞(第0天)分装于RNA稳定液(RNAlater solution;Ambion)并储存于-20℃以待后续使用,剩余细胞则分别接种至另三个35mm培养盘,于37℃培养隔夜。其后,该三盘细胞中的一盘细胞以30μM化疗药物依托泊西(etoposide)处理,另一盘细胞以30μM依托泊西及0.5mg/mL刺梨水萃取物处理,余下一盘细胞不予药物及刺梨萃取物处理而作为控制组。经过5天培养,收集该三组细胞(第5天)。藉由核酸自动萃取系统(tacoTM automatic nucleic acid extraction system;GeneReachBiotechnology)及随附DNA萃取套组(tacoTM DNA/RNA extraction kit)自前述第0天及第5天收集得的细胞中获得基因体DNA,用于qPCR及端粒长度测定。如图8所示,相对于控制组细胞,依托泊西的处理使端粒的相对长度明显缩短,但刺梨水萃取物的处理却能减缓此端粒缩短现象,说明刺梨萃取物能维持受化学伤害的端粒的长度。
4.2对抗紫外线(UV)照射所致端粒缩短
CCD-966SK细胞依1.5×105个细胞/盘接种于各含有2mL MEM细胞培养基的三个35mm培养盘,在37℃下培养隔夜后,其中二盘细胞予以1J/cm2 UVA(波长320-400nm)照射,另一盘细胞不予UVA照射而设为控制组。自各培养盘取半数细胞(第0天)分装于RNA稳定液(RNAlater solution;Ambion)并储存于-20℃以待后续使用,剩余细胞则分别接种至另三个35mm培养盘,于37℃培养隔夜。其后,该二盘经UVA照射细胞中的一盘细胞以0.5mg/mL刺梨水萃取物处理,另一盘细胞不予处理。经过二次继代培养且每次重复前述紫外线照射步骤,收集该三组细胞(第7天)。藉由核酸自动萃取系统(tacoTM automatic nucleic acidextraction system;GeneReach Biotechnology)及随附DNA萃取套组(tacoTM DNA/RNAextraction kit)自前述第0天及第7天收集得的细胞中获得基因体DNA,用于qPCR及端粒长度测定。图9显示刺梨水萃取物对紫外线照射所致皮肤细胞端粒缩短的抑制作用。如图9所示,相对于控制组细胞,UVA照射使端粒的相对长度明显缩短,但刺梨水萃取物的处理却能大幅减少此端粒缩短现象,说明刺梨萃取物能维持因紫外线受损的端粒的长度,即刺梨萃取物具有抗光老化作用。
综上所述,上述实验显示刺梨萃取物能同时减少氧化压力或发炎造成的细胞损伤及维持基因、蛋白质、及粒线体的正常运作,并且能增加端粒酶反应与减少端粒因化学药物或紫外线照射而受损,最终导致细胞回春的效果。因此,本发明提供刺梨萃取物用于制备细胞回春组合物的用途,该组合物可为粉末状、颗粒状、液状、胶状或膏状,且可制成食品、饮品、药品、试剂或营养补充剂,藉由口服、皮肤涂抹等方式给予一个体。
Claims (14)
1.一种刺梨萃取物用于制备细胞回春组合物的用途,其中该刺梨萃取物是以一溶剂萃取一刺梨而获得。
2.根据权利要求1所述的用途,其特征在于,所述溶剂为水、醇类、或醇水混合物。
3.根据权利要求1所述的用途,其中该刺梨萃取物促进一端粒酶的合成。
4.根据权利要求3所述的用途,其特征在于,所述刺梨萃取物增强端粒酶反转录酶(TERT)、端粒酶核醣核酸组分(TERC)、或其组合的基因表现。
5.根据权利要求1所述的用途,其特征在于,所述刺梨萃取物减少染色体端粒因化学药物或紫外线照射而长度缩短。
6.根据权利要求1所述的用途,其特征在于,所述刺梨萃取物促进基因修复。
7.根据权利要求6所述的用途,其特征在于,所述刺梨萃取物增强DNA修复蛋白的基因表现,所述DNA修复蛋白是选自于由MPG、ERCC6、XRCC5、及其任意组合所组成的群组。
8.根据权利要求1所述的用途,其特征在于,所述刺梨萃取物促进伴随蛋白T复合体的合成。
9.根据权利要求8所述的用途,其特征在于,所述刺梨萃取物增强该伴随蛋白T复合体(CCT)的蛋白次单元的基因表现,该蛋白次单元是选自于由CCT2、CCT5、CCT6A、CCT7、CCT8、及其任意组合所组成的群组。
10.根据权利要求1所述的用途,其特征在于,所述刺梨萃取物提升粒线体活性。
11.根据权利要求10所述的用途,其特征在于,所述刺梨萃取物抑制聚二磷酸腺苷核糖聚合酶(PARP)的基因表现,该PARP是选自于由PARP1、PARP3、PARP4、PARP8、PARP11、及其任意组合所组成的群组。
12.根据权利要求1所述的用途,其特征在于,所述溶剂与该刺梨的液固比为5~20∶1~5。
13.根据权利要求1所述的用途,其特征在于,所述萃取是在50℃~100℃进行。
14.根据权利要求1所述的用途,其特征在于,所述刺梨萃取物是刺梨的水萃取物,其浓度为至少0.5mg/mL。
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