CN108014118B - 一种三七皂苷Ft1的用途 - Google Patents
一种三七皂苷Ft1的用途 Download PDFInfo
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- CN108014118B CN108014118B CN201711416726.3A CN201711416726A CN108014118B CN 108014118 B CN108014118 B CN 108014118B CN 201711416726 A CN201711416726 A CN 201711416726A CN 108014118 B CN108014118 B CN 108014118B
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- notoginsenoside
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Abstract
本发明公开了一种三七皂苷Ft1的用途,所述用途是指以三七皂苷Ft1作为活性成分用于制备TGR5激动剂。本发明研究表明:三七皂苷Ft1具有显著的TGR5激动活性,可作为TGR5激动剂的有效成分。并且,本发明以C57BL/6J小鼠为研究对象,验证了三七皂苷Ft1作为TGR5激动剂使用时,能有有效改善小鼠的脂质代谢、糖代谢及胰岛素敏感性,可应用于制备预防和/或治疗代谢性疾病的药物和保健食品,尤其可望用于制备预防和/或治疗糖代谢异常、脂质代谢异常或/和胰岛素敏感异常的疾病的药物或保健食品。
Description
技术领域
本发明涉及一种三七皂苷Ft1的用途,属于医药技术领域。
背景技术
随着社会的发展,饮食结构的改变,肥胖症的患病率呈快速上升趋势,并且已经成为全球性公共卫生问题。世界卫生组织(WHO)调查数据显示,截至2005年,全球的肥胖发病率已占到成年人口的33%,而预计到2030年,其发病率将达到57.8%。肥胖症已成为危害人们健康的疾病,它与多种疾病的发生发展有着重要的关联,肥胖症跟糖尿病关系密切,跟2型糖尿病(type 2diabetes mellitus,T2DM)关系尤为密切,中国超重与肥胖人群的糖尿病患病率分别为12.8%和18.5%;而在糖尿病患者中超重比例为41%、肥胖比例为24.3%、腹型肥胖(腰围≥90cm(男)或≥85cm(女))患者高达45.4%。2010年中国糖尿病流行病学调查以糖化血红蛋白(hemoglobin A1c,HbA1C)≥6.5%作为诊断标准之一数据显示,中国成人糖尿病患病率高达11.6%,糖尿病患者人数居全球首位。尤其可见,肥胖症和糖尿病已成为威胁人类健康的严重疾病。
肥胖症和糖尿病都需要长期的治疗,目前肥胖症和糖尿病的治疗方法主要包括非药物调节(包括饮食、生活习惯、运动)、药物治疗以及手术治疗。但是目前临床使用的用于肥胖症和/或糖尿病治疗的降糖药或降脂药作用单一,治疗效果不佳,例如:目前常用的调血脂药物主要有HMG-CoA还原酶抑制剂(他汀类)、苯氧酸类(贝特类)、胆酸结合树脂、烟酸类药物、胆固醇吸收抑制剂及其它调血脂药物;这些药物主要是通过减少胆固醇吸收,抑制脂质合成,加速其分解,进而调节脂质代谢。
G蛋白偶联受体(Guanosine-binding Protein Coupled Receptor,简称GPCR)是细胞信号转导中的重要蛋白质,也是最主要的药物靶点,现有500多种潜在药物靶点中,GPCRs占据了大多数,其中,G-蛋白偶联胆汁酸受体(G protein-coupled receptorforbile acids,TGR5/GPBAR1)是近年来报道的糖尿病和高脂血症新药研究的热点靶点之一,它可以通过对细胞内的信号调控参与多种代谢通路的调节。研究表明:胆汁酸受体TGR5激动剂可在降血糖的同时改善肥胖,因此寻找开发TGR5激动剂为肥胖和糖尿病的治疗提供了新的思路和方向。
三七皂苷Ft1(Notoginsenoside Ft1)是一种天然的皂苷类化合物,主要存在于三七中,其分子式为:C47H80O17,化学结构式如下:
R=H;R1=Xyl1-2Glc1-2Glc。
目前,关于三七皂苷Ft1的药理活性报道主要是降血脂、抗肿瘤、消除氧自由基、抗氧化作用,至今未见三七皂苷Ft1作为TGR5激动剂用途的相关报道。
发明内容
针对现有技术存在的上述问题,本发明的目的是提供三七皂苷Ft1的新用途,以拓宽三七皂苷Ft1的应用价值。
本发明所述的三七皂苷Ft1的用途,是指以三七皂苷Ft1作为活性成分用于制备TGR5激动剂。
进一步说,本发明所述的三七皂苷Ft1的用途,是指以三七皂苷Ft1作为活性成分用于制备预防和/或治疗由TGR5介导的代谢性疾病的药物或保健食品。
更进一步说,所述的代谢性疾病包括但不限于:代谢综合征、糖尿病(更佳的为2型糖尿病)、胰岛素敏感、高血脂症、肥胖症、动脉粥样硬化、脂肪肝和/或它们的并发症。
作为优选方案,以三七皂苷Ft1作为活性成分用于制备预防和/或治疗糖代谢异常、脂质代谢异常或/和胰岛素敏感异常的疾病的药物或保健食品。
作为进一步优选方案,以三七皂苷Ft1作为活性成分用于制备预防和/或治疗肥胖症、糖尿病、高脂血症中的至少一种疾病的药物或保健食品。
本发明所述活性成分的有效施用剂量可随所用的药物、给药的模式和待治疗的疾病的严重程度而变化。然而,通常当本发明的活性化合物每天以约0.5-30mg/kg体重的剂量给予时,能得到令人满意的效果,较佳地每天以1-3次分开的剂量给予,或以缓释形式给药。
本领域技术人员应理解,本发明中所述的三七皂苷Ft1可通过商业途径购买获得,也可通过多种本领域熟知的方法、利用公知的原料获得,比如化学合成或从植物中提取得到(例如从五加科科植物三七中分离获得)。
本发明的三七皂苷Ft1可以单独使用或以药物组合物的形式使用。药物组合物包括作为活性成分的本发明的三七皂苷Ft1及可药用载体。较佳地,本发明的药物组合物含有0.1-99.9%重量百分比的作为活性成分的本发明的三七皂苷Ft1。“可药用载体”不会破坏本发明的三七皂苷Ft1的药学活性,同时其有效用量,即能发挥药物载体作用时的用量对人体无毒。
所述可药用载体包括但不限于:软磷脂、硬脂酸铝、氧化铝、离子交换材料、自乳化药物传递系统、吐温或其他表面活化剂、血清蛋白、缓冲物质如磷酸盐、氨基乙酸、山梨酸、水、盐、电解质如硫酸盐精蛋白、磷酸氢二钠、磷酸氢钾、氯化钠、锌盐、硅酸镁、饱和脂肪酸部分甘油酯混合物等。
其他常用的药物辅料如粘合剂(如微晶纤维素)、填充剂(如淀粉、葡萄糖、无水乳糖和乳糖珠粒)、崩解剂(如交联PVP、交联羧甲基淀粉钠、交联羧甲基纤维素钠、低取代羟丙基纤维素)、润滑剂(如硬脂酸镁)以及吸收促进剂、吸附载体、香味剂、甜味剂、赋形剂、稀释剂、润湿剂等。
本发明的三七皂苷Ft1以及其药物组合物可按本领域常规方法制备并可以通过肠道或非肠道或局部途径给药。口服制剂包括胶囊剂、片剂、口服液、颗粒剂、丸剂、散剂、丹剂、膏剂等;非肠道给药制剂包括注射液等;局部给药制剂包括霜剂、贴剂、软膏剂、喷雾剂等。优选为口服制剂。
本发明的三七皂苷Ft1以及其药物组合物的给药途径可以为口服、舌下、经皮、经肌肉或皮下、皮肤粘膜、静脉、尿道、阴道等。
除了制成药物之外,亦可在本发明的三七皂苷Ft1中加入抗氧化剂、色素、酶制剂等各种食品添加剂,按本领域的常规方法制成保健食品。
与现有技术相比,本发明具有如下显著性有益效果:
本发明的研究结果显示:三七皂苷Ft1具有显著的TGR5激动活性,可作为TGR5激动剂的有效成分。并且,本发明以C57BL/6J小鼠为研究对象,验证了三七皂苷Ft1作为TGR5激动剂使用时,能有有效改善小鼠的脂质代谢、糖代谢及胰岛素敏感性,可应用于制备预防和/或治疗代谢性疾病的药物和保健食品,尤其可望用于制备预防和/或治疗糖代谢异常、脂质代谢异常或/和胰岛素敏感异常的疾病的药物或保健食品,具有广泛的应用前景。
附图说明
图1体现了从三七中分离出的十种不同皂苷成分的TGR5荧光素酶基因活性检测结果;图中:a、b、c、d、e、f、g、h、i、j分别表示三七皂苷R1、绞股蓝皂苷Ⅸ、三七皂苷R2、三七皂苷Fe、三七皂苷Ft1、人参皂苷Rc、人参皂苷Re、人参皂苷Rh1、人参皂苷Rh2、人参皂苷Rb2;
图2体现了三七皂苷Ft1对TGR5介导的cAMP的形成的影响结果;
图3体现了三七皂苷Ft1与TGR5受体的计算机模拟分子对接分析结果;其中:图3A是化学结构式,图3B是三维结构图;
图4体现了三七皂苷Ft1对肥胖小鼠的体重影响;其中:图4A是野生小鼠的体重变化;图4B是野生小鼠的进食量变化;图4C是TGR5敲除小鼠的体重变化;图4D是TGR5敲除小鼠的进食量变化;
图5体现了三七皂苷Ft1对肥胖小鼠的肝脏及附睾周围脂肪组织形态的影响;其中:图5A肝脏的HE染色切片,图5B是附睾周围脂肪组织切片;
图6体现了三七皂苷Ft1对肥胖小鼠的体脂重量、肝脏重量、附睾脂肪组织重量、肝脏中甘油三酯和总胆固醇含量的影响;其中:图6A是体脂重量的体脂重量,图6B是体脂重量的肝脏重量;图6C是两种小鼠的附睾脂肪组织重量;图6D是两种小鼠的肝脏中甘油三酯含量;图6E是两种小鼠的肝脏中总胆固醇含量;
图7体现了三七皂苷Ft1对肥胖小鼠的糖代谢影响;其中:图7A是野生小鼠空腹血糖水平;图7B是野生小鼠给予葡萄糖后血糖水平;图7C是野生小鼠给予葡萄糖后血糖的曲线下面积;图7D是TGR5敲除小鼠空腹血糖水平;图7E是TGR5敲除小鼠给予葡萄糖后血糖水平;图7F是TGR5敲除小鼠给予葡萄糖后血糖的曲线下面积;
图8体现了三七皂苷Ft1对肥胖小鼠的胰岛素敏感性影响;其中:图8A是野生小鼠空腹胰岛素水平;图8B是野生小鼠给予胰岛素后血糖水平;图8C是野生小鼠给予胰岛素后血糖的曲线下面积;图8D是TGR5敲除小鼠空腹胰岛素水平;图8E是TGR5敲除小鼠给予胰岛素后血糖水平;图8F是TGR5敲除小鼠给予胰岛素后血糖的曲线下面积。
具体实施方式
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法,通常按照常规条件或按照制造厂商所建议的条件。除非另外说明,否则百分比和份数按重量计算。
1.材料与试剂
1.1主要仪器和设备
精密天平(Sartorius,德国);
1X20全自动生化分析仪(Beckman,美国);
体温计(Physitemp Instruments,Inc.,美国);
血糖仪(Johnson&Johnson,美国);
超声粉碎仪Soniprepl50Ultrasonic Disintegrator(MSE,英国);
酶标仪分光光度计(BioTek,美国);
超净工作台(Heal Force);
-80℃低温冰箱(Thermo Fisher);
G154DW立式自动压力蒸汽灭菌锅(Schneider Electric)。
1.2主要试剂与耗材
三七皂苷Ft1(分子量:917.13,HPLC纯度≥99%,中药研究所);
优泌林精蛋白锌重组人胰岛素混合注射液(Lilly,美国);
胰岛素测定ELISA试剂盒(Linco,美国);
血清游离脂肪酸测定试剂(Wako,日本);
lml无菌注射器(BD、美国);
0.45μm滤器(MiUipore、美国);
血糖试纸(Johnson&Johnson,美国)。
2、实验方法
2.1TGR5稳转细胞株的建立
HEK293细胞用DMEM培养液(含10%胎牛血清、100mg·L-1链霉素和青霉素100U·L-1)置于37℃含5%CO2培养箱中常规培养,2天换液一次,取对数生长期的细胞用于实验。MouseTGR5表达质粒(pIRESneo3-mTGR5)用Lipofectamine 2000进行转染,48小时候细胞转移至含500mg/mL G418的培养基中,筛选耐药的单克隆并real-time PCR检测TGR5的表达,最后挑选得到稳定转mTGR5的细胞株。
2.2细胞转染(24孔板为例)
HEK293TGR5稳转细胞株转染前更换为无抗生素的完全培养基培养。采用脂质体进行瞬时转染,操作步骤参考Lipofectamine 2000试剂盒说明书,将200ng/well pCRE-lucreporter质粒,5ng/wellβ-Gal质粒与50μl/well OPTI-MEM I型无血清培养液轻柔匀,取1μl/well混匀后的Lipofectamine 2000与50μl/well OPTI-MEM无血清培养液轻柔混匀,室温下静置5min;
将含有质粒的50μl/well OPTI-MEM与Lipofectamine 2000稀释液轻柔混匀,室温下静置20min将质粒,Lipofectamine 2000脂质体复合物100μl/well加入细胞,并轻柔摇晃24孔板使其混合均匀,转染后6小时更换新鲜的含抗生素的完全培养液,并加检测的化合物和阳性对照LCA(10μM/L)。
2.3荧光素酶指示的启动子报告基因活性检测
操作步骤参考Luciferase Reporter Assay System(Promega公司)试剂说明书。
细胞经质粒转染及加药干预后,PBS清洗两遍,每孔加入100μl的PLB裂解液室温下300rpm晃动裂解15分钟,将细胞裂解液收集到1.5ml EP管中13000g、4℃离心10分钟取20μl上清至96孔板检测,每个样品2复孔,每孔加入100μl的luciferase试剂,置混匀器上混匀后,立刻检测;β-gal reagent和dilution buffer以1:50稀释备用,以96孔板检测,每个样品2复孔,分别加入10μl细胞上清液和100μlβ-gal试剂,将细胞板放入96孔板混匀器上摇晃混匀1小时后,至荧光分光光度计测量;将两次数值之比做为最终检测结果进行统计分析。
2.4cAMP检测
将HEK293TGR5过表达细胞株,在无血清的添加100mM Ro 20-1274和500mM IBMX(Sigma,St.Louis,MO)的Krebs Ringer缓冲液中用Ft1和LCA处理30分钟,根据cAMP-GloAssay Kit(Promega)说明书,将细胞裂解液用于测定cAMP的含量。
2.5实验动物
C57BL/6J(WT)野生型雄性小鼠购自Jackson实验室(Bar Harbor,ME),以C57BL/6J为背景的TGR5基因敲除小鼠(TGR5KO)由默克公司的Dr.Vassileva Galya at Merck赠送,体重20±2g的C57BL/6雄性小鼠与TGR5KO雄性小鼠,饲养于希望之城国家医学研究中心实验动物中心。
SPF级饲养室饲养环境:温度15~25℃,相对湿度45~55%,12小时交替照明,饲料和水新鲜无污染,自由摄食和饮水;动物适应环境一周后,所有小鼠进行食高脂饲料(Research Diets,New Brunswick,NJ,D12492)或正常饲料喂养;6周后进行分组:正常对照组(Vehicle)、高脂模型组(HFD)、三七皂苷Ft1(30mg/kg)组;野生型和TGR5基因敲除正常对照组和实验组小鼠分别继续以正常饲料和高脂饲料饲养6周,同时口服给药6周,并每周测量小鼠的体重和摄食量;实验结束前测定小鼠空腹血糖值,测定前禁食12小时,并进行葡萄糖耐量和胰岛素耐量测试;摘眼收集小鼠血液以测定血清指标,取小鼠肝脏以测定肝脏脂质指标。
2.6葡萄糖耐量(IPGTT)及胰岛素耐量(IPITT)实验
小鼠禁食12-16小时后测定空腹血糖之后,腹腔注射葡萄糖(1.5g·kg-1体重),分别于15、30、60及120分钟检测小鼠血糖。
胰岛素耐量实验(ITT):小鼠禁食4-6小时后,腹腔注射胰岛素(0.75U·kg-1体重),分别于0、15、30、60及120分钟采血测血糖.
2.7血清和肝脏生化指标测定
全血室温静置2小时,4℃离心15分钟(3500rpm),取上层血清,按酶联免疫试剂盒所述方法测定并计算血清中胰岛素(Insulin)水平。
另称取小鼠肝脏50mg,加入0.5ml组织裂解液后超声粉碎均浆,加入0.5ml氯仿后涡旋30秒,3000rpm离心15分钟后取氯仿层,挥干氯仿后用50μl异丙醇复溶,测定总总甘油三酯(TG)和总胆固醇(TC)含量。
2.8病理组织学分析
2.8.1肝脏和脂肪组织HE染色:
(1)切取相同部位(肝大叶)的部分肝组织和脂肪组织,10%中性福尔马林固定,常规石蜡包埋,4~5μm厚度连续切片,放在载玻片上;
(2)脱蜡:依次经二甲苯Ⅰ浸没5分钟、二甲苯Ⅱ浸没5分钟、无水乙醇浸没5分钟、90%乙醇浸没3分钟、80%乙醇浸没3分钟,最后用蒸馏水浸洗3分钟;
(3)苏木素染色:先经苏木素染色约3分钟,然后自来水冲洗1分钟;
(4)将载玻片放入0.5%的伊红溶液中30秒,然后自来水冲洗1分钟;
(5)脱水:载玻片依次放入95%乙醇中2分钟、无水乙醇中2分钟、二甲苯Ⅰ中2分钟,最后放入二甲苯Ⅱ中5分钟;
(6)将载玻片于60℃恒温干燥箱中烤干,用50%中性树胶二甲苯溶液封片,晾干,显微镜下观察肝脏组织和脂肪组织的形态变化。
2.8.2肝脏组织油红O染色:
(1)配制油红O储备液:0.5g油红O溶于100ml异丙醇中,60℃水浴锅温浴1小时,期间不时振荡,用时将油红O储备液与双蒸水以3:2的比例混合均匀,然后过滤除去杂质,滤液即为油红O工作液;
(2)切取各组小鼠相同部位(肝大叶)的部分肝脏组织,先用4%多聚甲醛固定,Tissue-Tek OCT包埋剂包埋肝组织,于-80℃冷冻保存;
(3)于冰冻切片机上切取10μm厚度的连续切片;
(4)待玻片上的组织稍干后(避免太干以防组织裂开),滴加60%异丙醇浸润组织,然后弃之;
(5)滴加油红O工作液,染色约10分钟;
(6)弃去油红O工作液,60%异丙醇洗3次,流水冲洗30秒;
(7)苏木素室温染4分钟;
(8)弃去苏木素染料,流水冲洗30秒,用甘油明胶封片,晾干,显微镜下观察肝脏组织的形态变化。
2.9数据处理
所有数据用means±s.e.m.表示,采用SPSS 19.0软件进行分析;多组间比较采用One-way ANOVA处理,方差齐使用LSD-t法,方差不齐使用Dunnett法,以P<0.05表示差异有统计学意义。
3、实验结果
3.1三七皂苷中靶向TGR5活性成份的筛选结果
三七为五加科多年生草本植物三七Panax notoginseng(Burk)F.H.Chen的根,三七含有多种化学成分,主要有效成分之一是皂苷类,对三七中一些皂苷成分进行TGR5激动活性进行比较。
图1是从三七中分离出的十种不同皂苷成分的TGR5荧光素酶基因活性检测结果,由图1可见:与空白组相比,从三七中分离的十种皂苷(三七皂苷R1、绞股蓝皂苷Ⅸ、三七皂苷R2、三七皂苷Fe、三七皂苷Ft1、人参皂苷Rc、人参皂苷Re、人参皂苷Rh1、人参皂苷Rh2、人参皂苷Rb2)中仅三七皂苷Ft1显示出与阳性药LCA相似的TGR5的激动活性,在10μm/L浓度下,LCA的激动作用是空白对照的6.1倍,而三七皂苷Ft1的激动作用是空白对照的3.8倍(图1)。
图2体现了三七皂苷Ft1对TGR5介导的cAMP的形成的影响结果,由图2可见:三七皂苷Ft1能显著增加TGR5介导的cAMP的形成,其中LCA的EC50是0.59μm/L,三七皂苷Ft1的EC50是2.93μm/L。
结合图1和图2可见,三七皂苷Ft1具有显著的TGR5激动活性,可作为胆汁酸膜受体TGR5激动剂使用。
3.2三七皂苷Ft1与TGR5受体的计算机模拟分子对接分析
利用计算机模拟分子对接技术发现,三七皂苷Ft1与TGR5受体结合,与活性残基L263,Y240,G260及S157有结合,并形成氢键(见图3所示),由此可判断三七皂苷Ft1是TGR5激动剂。
3.3三七皂苷Ft1对肥胖小鼠脂质代谢的影响
体外筛选结果显示三七皂苷Ft1是胆汁酸膜受体TGR5的激动剂,因而我们用肥胖小鼠(经正常饲料、高脂饲料喂食小鼠或高脂饲料喂食小鼠并口服给予三七皂苷Ft1(30mg/kg)6周)对三七皂苷Ft1的体内作用进行评价。
首先,观察小鼠的体重和进食量的变化:野生型小鼠经过六周口服给予三七皂苷Ft1后,小鼠体重显著降低,但是三七皂苷Ft1未能影响进食量(见图4A和图4B所示),说明三七皂苷Ft1对小鼠体重的影响不是通过降低食欲引起的;另外,同样TGR5基因敲除小鼠经过六周口服给予三七皂苷Ft1后,小鼠体重和进食量未有显著变化(见图4C和图4D所示),说明三七皂苷Ft1可通过TGR5影响小鼠体重的变化。
其次:观察肝脏及脂肪组织中的脂质代谢:野生型小鼠给予三七皂苷Ft1后,肝脏病理切片结果显示,肝脏中脂滴的积累显著减轻(见图5A所示),附睾周围脂肪组织切片亦显示三七皂苷Ft1组减小脂肪细胞大小(见图5B所示);而TGR5基因敲除小鼠给予三七皂苷Ft1后肝脏及附睾周围脂肪组织中脂质的积累与高脂饲料喂食的高脂组比无显著差异(见图5A和图5B所示);另外,野生型小鼠给予三七皂苷Ft1后,体脂重量、肝脏重量、附睾脂肪组织重量、肝脏中TG和TC含量与高脂组相比均显著降低,而TGR5基因敲除小鼠给予三七皂苷Ft1后未能显示出显著差异(见图6A至6E所示);图5和图6的结果说明三七皂苷Ft1可通过TGR5影响小鼠体内脂质代谢。
结合图4、图5和图6可见:三七皂苷Ft1可通过TGR5影响小鼠体重和体内脂质代谢,进而说明三七皂苷Ft1有利于脂质代谢性疾病的治疗,对肥胖症具有显著的治疗作用。
3.4三七皂苷Ft1对肥胖小鼠糖代谢及胰岛素敏感性的影响
考察三七皂苷Ft1对肥胖小鼠(经正常饲料、高脂饲料喂食小鼠或高脂饲料喂食小鼠并口服给予三七皂苷Ft1(30mg/kg)6周)糖代谢及胰岛素敏感性的影响。
葡萄糖耐量实验结果显示:野生型小鼠给予三七皂苷Ft1六周后,空腹血糖值和胰岛素水平显著低于高脂组(见图7A和图8A所示),给予葡萄糖后野生型小鼠各时间点血糖值均低于高脂组小鼠,且血糖达到峰值的时间提前(见图7B所示),两组小鼠血糖的曲线下面积具有统计学差异(见图7C所示);胰岛素耐量实验结果显示:给予0.75U/kg胰岛素后,野生型小鼠各时间点血糖值均低于高脂组小鼠(见图8B所示),两组小鼠血糖的曲线下面积具有统计学差异(见图8C所示);而对于基因敲除鼠给予6周三七皂苷Ft1,均未能改善GTT(糖耐受)和ITT(胰岛素耐受)(见图7D至图7F、图8D至图8F所示)。说明三七皂苷Ft1可通过TGR5改善肥胖小鼠的糖代谢与胰岛素敏感性。
结合图7和图8可见,三七皂苷Ft1可通过TGR5改善肥胖小鼠的糖代谢与胰岛素敏感性,进而说明三七皂苷Ft1有利于糖代谢和胰岛素敏感性疾病的治疗,对糖尿病具有显著的治疗作用。
3.3和3.4的研究结果表明:Ft1作为胆汁酸膜受体TGR5的配体能通过激活TGR5参与肥胖小鼠机体内糖脂代谢的调控,因此,Ft1可以作为治疗肥胖及二型糖尿病的先导化合物。
综上所述,本发明所述的三七皂苷Ft1具有显著的TGR5激动活性,可作为TGR5激动剂的有效成分,可望用于制备预防和/或治疗代谢性疾病的药物和保健食品,尤其可望用于制备预防和/或治疗糖代谢异常、脂质代谢异常或/和胰岛素敏感异常的疾病的药物或保健食品,具有广泛的应用前景。
最后需要在此指出的是:以上仅是本发明的部分优选实施例,不能理解为对本发明保护范围的限制,本领域的技术人员根据本发明的上述内容做出的一些非本质的改进和调整均属于本发明的保护范围。
Claims (1)
1.一种三七皂苷Ft1的用途,其特征在于:以三七皂苷Ft1作为唯一活性成分用于制备预防和/或治疗肥胖症、糖尿病、胰岛素抵抗、脂肪肝中的至少一种疾病的药物。
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