CN115177627A - 苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用 - Google Patents
苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用 Download PDFInfo
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Abstract
本发明涉及生物医药技术领域。本发明提供了苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用。本发明确定管花肉苁蓉苯乙醇苷对鼠源3T3‑L1前脂肪细胞分化及脂质积累具有明显抑制作用,并显著改善高脂饮食诱导的肥胖小鼠胰岛素抵抗,可用于制备抗肥胖相关糖尿病药物。
Description
技术领域
本发明涉及生物医药技术领域,尤其涉及苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用。
背景技术
在过去几十年当中,全球糖尿病的发病率在不断增高,根据国际糖尿病联盟最新报告,2019年全球约4.63亿人(20~79岁)患DM,患病率为9.3%。 2020年中国糖尿病流行病学数据显示,中国成年人DM患病率为12.8%,DM患者总人数近1.3亿。因此,DM严重危害人类生命健康,并已成为我国迫切需要解决的卫生健康问题,迫切需要寻找和开发高效低毒新抗糖尿病的新药。
管花肉苁蓉为传统补益类中草药,具有抗肿瘤、抗氧化、抗炎、免疫增强等多种生物活性,含有苯乙醇苷类、萜类、多糖等多种成分。苯乙醇苷为管花肉苁蓉主要活性成分之一,是一类酚苷类化合物,其特征是苯乙醇部分通过糖苷键与β-吡喃葡萄糖/β-戊基葡萄糖连接,具有抗肿瘤、抗炎、抗氧化、神经保护等生物活性。因此,管花肉苁蓉苯乙醇苷具有良好的药用及保健品开发价值。
发明内容
本发明的目的在于提供一种苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用,开发一种高效低毒抗糖尿病的药物。
为了实现上述发明目的,本发明提供以下技术方案:
本发明提供了苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用。
作为优选,所述苯乙醇苷来源于管花肉苁蓉。
本发明提供了苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用。本发明确定管花肉苁蓉苯乙醇苷对鼠源3T3-L1前脂肪细胞分化及脂质积累具有明显抑制作用,并显著改善高脂饮食诱导的肥胖小鼠胰岛素抵抗,可用于制备抗肥胖相关糖尿病药物。
附图说明
图1为管花肉苁蓉苯乙醇苷对3T3-L1前脂肪细胞脂肪分化及脂质积累的抑制效应,其中(A)为管花肉苁蓉苯乙醇苷对3T3-L1细胞活性的影响; (B)为管花肉苁蓉苯乙醇苷处理3T3-L1前脂肪细胞并诱导脂肪分化形态学变化,并用油红O染色鉴定,放大倍数均为200倍;(C)为脂质生成半定量分析;(D)和(E)分别为甘油三酯(TG)和游离脂肪酸(NEFA)含量。数据以平均值±标准差表示,Untreated:阴性对照组,#表示与Untreated组比较具有显著性差异,P<0.05;MDI(分化诱导剂):模型组,*表示与MDI 组相比具有显著性差异,P<0.05。
图2为管花肉苁蓉苯乙醇苷改善胰岛素抵抗状态下3T3-L1脂肪细胞 (IR-3T3-L1)糖脂代谢;(A)建立IR-3T3-L1细胞模型,(B)管花肉苁蓉苯乙醇苷处理IR-3T3-L1细胞48h,上清液葡萄糖消耗量,(C)NEFA含量, (D)TG含量;数据以平均值±标准差表示,二甲双胍(MET):阳性对照组,Untreated:阴性对照组,MDI:IR模型组,管花肉苁蓉苯乙醇苷处理组;#表示与Untreated组比较具有显著性差异,P<0.05;*表示与MDI组相比具有显著性差异,P<0.05。
图3为管花肉苁蓉苯乙醇苷对HFD小鼠葡萄糖耐量和胰岛素耐量的改善作用;管花肉苁蓉苯乙醇苷连续灌胃给药模型小鼠第5周和第6周分别进行(A)口服葡萄糖耐量实验(OGTT)和(B)胰岛素耐量实验(ITT),数据以平均值±标准差表示,#表示与正常饮食对照小鼠(NFD)比较具有显著性差异,P<0.05;*表示与高脂饮食模型小鼠(HFD)比较具有显著性差异, P<0.05。
图4为管花肉苁蓉苯乙醇苷对HFD小鼠血脂异常的改善作用;管花肉苁蓉苯乙醇苷给药6周后,小鼠血清TC(A)、TG(B)、LDL(C)和TBA (D)水平变化;数据以平均值±标准差表示,#表示与NFD组比较具有显著性差异,P<0.05;*表示与HFD组比较具有显著性差异,P<0.05。
图5为管花肉苁蓉苯乙醇苷对HFD小鼠脂肪组织形态的保护作用;管花肉苁蓉苯乙醇苷给药6周后,各组小鼠eWAT(A)、pWAT(B)、iWAT(C) 重量指数的变化;pWAT和iWAT脂肪组织大小(D)变化;组织病理学变化(E)与脂肪细胞大小变化(F);数据以平均值±标准差表示,#表示与NFD 组比较具有显著性差异,P<0.05;*表示与HFD组比较具有显著性差异, P<0.05。
图6为管花肉苁蓉苯乙醇苷对HFD小鼠肝脏组织和代谢的改善作用;管花肉苁蓉苯乙醇苷给药6周后,小鼠肝脏重量(A),肝脏指数(B),血清ALT(C)和AST(D)水平、肝脏形态(E)变化,肝组织切片H&E染色(F),肝组织TG(G)、TC(H)含量和AMPK蛋白表达水平(I)变化;数据以平均值±标准差表示,#表示与NFD组比较具有显著性差异,P<0.05; *表示与HFD组比较具有显著性差异,P<0.05。
图7为管花肉苁蓉苯乙醇苷通过调节IRS1/Akt信号通路改善HFD小鼠的胰岛素抵抗;管花肉苁蓉苯乙醇苷给药6周后,小鼠随机血糖(A),空腹血糖(B),空腹胰岛素(C)水平以及HOMA2指数:胰岛素抵抗(HOMA2-IR) (D),胰岛素敏感性(HOMA2-%S)(E),β细胞功能(HOMA2-%B)(F) 指数变化;WB检测小鼠eWAT中胰岛素信号分子表达以及磷酸化水平(G),并对WB蛋白条带进行灰度扫描定量分析后pIRS1/IRS1(H),pAkt-ser 473/Akt(I),pAkt-thr308/Akt(J)和GLUT4/GAPDH比值(K)变化。HOMA2:稳态模型评估2,IR:胰岛素抵抗,%B:β细胞百分比,%S:敏感性百分比;数据以平均值±标准差表示,#表示与NFD组比较具有显著性差异,P<0.05; *表示与HFD组比较具有显著性差异,P<0.05。
图8为管花肉苁蓉苯乙醇苷对HFD小鼠肠道菌群组成的影响;(A)为组间基因数目差异箱图,横坐标为各个分组信息:NFD,HFD,管花肉苁蓉苯乙醇苷(300mg/kg管花肉苁蓉苯乙醇苷给药组),纵坐标为基因数目;不同的小写字母表示有差异性(P<0.05);(B)为各组在门水平相对丰度柱形图,横坐标为各个分组信息:NFD,HFD,管花肉苁蓉苯乙醇苷;纵坐标为物种相对丰度;(C)为肠道微生物聚类分析图,横向为样品信息:NFD, HFD,管花肉苁蓉苯乙醇苷,phylum:门水平,class:纲水平;纵向为物种注释信息。(D)基于门水平的物种PCoA结果;(E)Bray-Curtis距离聚类树结构图;(F)基于显著性差异功能的丰度聚类热图。横坐标为各个分组信息。
具体实施方式
下面结合实施例对本发明提供的技术方案进行详细的说明,但是不能把它们理解为对本发明保护范围的限定。
实施例1管花肉苁蓉苯乙醇苷对3T3-L1脂肪细胞分化和脂质生成的抑制作用
为研究管花肉苁蓉苯乙醇苷对3T3-L1前脂肪细胞分化的影响,首先,以不同浓度的管花肉苁蓉苯乙醇苷处理3T3-L1前脂肪细胞48h并筛选管花肉苁蓉苯乙醇苷安全剂量。结果如图1A所示,管花肉苁蓉苯乙醇苷作用48 h时,200μg/mL管花肉苁蓉苯乙醇苷显著抑制细胞活性(P<0.05),由此选择后续实验中管花肉苁蓉苯乙醇苷作用浓度范围为25、50、75、100μg/mL。在3T3-L1脂肪细胞经MDI诱导分化的同时用管花肉苁蓉苯乙醇苷进行处理。结果如图1-B显示,Untreated组未形成脂滴,油红O染色结果呈阴性; MDI诱导模型组出现明显的脂滴,并被油红O染液染成红色。半定量结果显示,与MDI组相比,25、50、75、100μg/mL管花肉苁蓉苯乙醇苷显著抑制3T3-L1脂肪细胞脂滴的形成(图1-C)。进一步检测细胞内TG和细胞培养上清中NEFA的水平变化,发现管花肉苁蓉苯乙醇苷处理后,TG、NEFA 含量出现明显下降;与MDI组相比,TG含量分别降低了5.4%,27.5%,50.1%和67.6%(P<0.05),NEFA含量分别降低了331.%,39.8%,39.8%和45.9% (P<0.05)(图D和E);以上结果表明,管花肉苁蓉苯乙醇苷呈剂量依赖性地抑制脂肪分化,并显著抑制TG的生成和NEFA的释放。
实施例2管花肉苁蓉苯乙醇苷对3T3-L1脂肪细胞胰岛素抵抗和糖脂代谢的改善作用
确定3T3-L1前脂肪细胞分化为脂肪细胞后,设置对照组和模型组,采用DEX进行IR诱导并建立3T3-L1-IR模型进行后期实验。在IR状态下细胞葡萄摄取会受到抑制,因此可通过检测细胞葡萄糖消耗量来判断细胞是否出现IR。用1μmol/L DEX处理3T3-L1脂肪细胞继续培养并检测上清葡萄糖含量。结果如图2-A显示,DEX处理48h,与Untreated组相比,葡萄糖消耗量显著降低并可以维持到72h(P<0.05)。以上结果表明,3T3-L1细胞葡萄糖摄取能力显著减弱,细胞出现IR状态(IR-3T3-L1)。在IR-3T3-L1中,不同浓度的管花肉苁蓉苯乙醇苷作用48h后检测葡萄糖消耗量并以MET作为阳性对照。结果如图2-B显示,MET和75μg/mL管花肉苁蓉苯乙醇苷组细胞葡萄糖消耗量分别提高了38.7%和42.5%,具有显著差异(P<0.05);同时,细胞上清液中TG和NEFA水平分别降低了48.2%和51.7%(P<0.05)(图 2-C和D)。表明管花肉苁蓉苯乙醇苷可以显著促进IR-3T3-L1细胞葡萄糖消耗并降低脂质水平。
实施例3管花肉苁蓉苯乙醇苷显著改善HFD小鼠的葡萄糖耐量和胰岛素耐量异常
为考察管花肉苁蓉苯乙醇苷对高脂饮食(HFD)诱导的肥胖小鼠IR的影响,建立小鼠模型并对模型小鼠分别进行了口服葡萄糖耐量(OGTT)和胰岛素耐量(ITT)实验。在管花肉苁蓉苯乙醇苷给药第5周时进行了OGTT 实验,结果如图3-A所示,与HFD组相比,管花肉苁蓉苯乙醇苷给药组和 MET组在葡萄糖激发后15、30、60、120min均降低了血糖水平,其中0-120 min范围内相对血糖水平的曲线下面积(AUC)值显著降低(P<0.05)。以上结果表明,管花肉苁蓉苯乙醇苷显著改善HFD小鼠的葡萄糖不耐受。
在管花肉苁蓉苯乙醇苷给药第6周进行ITT实验并计算AUC。结果如图3-B所示,与HFD组相比,管花肉苁蓉苯乙醇苷给药组在腹腔注射胰岛素后30、60min时间点的相对血糖水平明显低于HFD组;同时,管花肉苁蓉苯乙醇苷处理组同MET组0-120min范围内相对血糖水平的曲线下面积 (AUC)值显著降低(P<0.05)。以上结果表明,管花肉苁蓉苯乙醇苷同MET一样能够改善HFD小鼠IR,且作用效果优于MET组。
实施例4管花肉苁蓉苯乙醇苷显著改善HFD小鼠的血脂异常
HFD诱导的肥胖小鼠出现了高血脂症,为考察管花肉苁蓉苯乙醇苷给药对模型小鼠脂代血脂异常影响,本研究检测了小鼠血清血脂指标。结果如图 4-A所示,与HFD组相比,管花肉苁蓉苯乙醇苷给药组显著降低了TC水平, (31.3%)(P<0.05),而对TG水平无显著影响(图4-B);LDL水平降低,但无统计学差异(P>0.05)(图4-C)。为了进一步研究管花肉苁蓉苯乙醇苷对TC的影响,检测TC最终分解产物总胆汁酸(TBA)水平;与HFD组相比,管花肉苁蓉苯乙醇苷给药组TBA水平有所升高(图4-D);因此,初步推测管花肉苁蓉苯乙醇苷可能会促进TC的分解代谢从而缓解血脂异常。
实施例5管花肉苁蓉苯乙醇苷显著改善HFD小鼠的脂肪组织肥大
小鼠连续灌胃给药6周实验结束后,取各组小鼠腹股沟白色脂肪组织 (iWAT)、附睾白色脂肪组织(eWAT)、肾周围白色脂肪组织(pWAT)分别称重并计算脂肪指数。结果显示,管花肉苁蓉苯乙醇苷给药在不影响小鼠体重和能量摄入的情况下,与HFD组相比,管花肉苁蓉苯乙醇苷给药组显著降低了HFD小鼠eWAT、iWAT、pWAT(图5-A-C)的重量指数。脂肪组织大小(图5-D)与以上结果一致。表明管花肉苁蓉苯乙醇苷通过抑制不同部位WAT的扩增,改善小鼠HFD诱导的肥胖,其中对iWAT和pWAT作用效果优于MET组。
为进一步明确管花肉苁蓉苯乙醇苷对脂肪组织的影响,本研究对小鼠不同部位WAT切片进行H&E染色。结果如图5-E显示,与NFD组相比,HFD 诱导的小鼠eWAT、iWAT和pWAT脂肪细胞明显变大,而管花肉苁蓉苯乙醇苷给药组脂肪细胞大小明显小于HFD组。应用Image J软件计算其图片中脂肪细胞大小发现,与NFD组相比,HFD组WAT细胞大小显著增加(P<0.05);与HFD组相比,管花肉苁蓉苯乙醇苷给药组显著降低了不同部位脂肪组织中脂肪细胞大小(P<0.05);管花肉苁蓉苯乙醇苷给药组eWAT、 iWAT和pWAT脂肪细胞面积分别减小了65%、45%和71%,而MET组分别减小了40%、33%和35%(图5-F-H)。以上结果表明,管花肉苁蓉苯乙醇苷可显著改善WAT脂肪细胞肥大,作用效果优于MET组。管花肉苁蓉苯乙醇苷可能通过抑制肥胖小鼠WAT扩张发挥抗肥胖及相关糖尿病作用。
实施例6管花肉苁蓉苯乙醇苷改善HFD小鼠肝损伤及肝脏脂肪变性
HFD诱导会引发小鼠肝功能损伤。为观察管花肉苁蓉苯乙醇苷对肝脏的影响,实验结束后解剖小鼠取各组小鼠肝脏分别称重并计算肝脏指数。结果如图6-A和B所示,与HFD组相比,管花肉苁蓉苯乙醇苷给药组对肝脏重量和肝脏指数有显著地恢复作用(P<0.05);进一步检测血清肝损伤指标谷丙转氨酶(ALT)和谷草转氨酶(AST),与HFD组相比,管花肉苁蓉苯乙醇苷给药组显著降低ALT水平(P<0.05),管花肉苁蓉苯乙醇苷给药组AST 水平低于HFD组,但无显著差异(图6-C和D);表明管花肉苁蓉苯乙醇苷显著改善HFD小鼠肝损伤,对肝脏有一定的保护作用。同时,各组肝脏形态变化显示,NFD组小鼠肝脏颜色暗红,HFD组小鼠肝脏“白色化”,管花肉苁蓉苯乙醇苷给药组部分恢复肝脏颜色,改变脂肪脂质变性,降低了肝脏脂肪沉积(图6-E),表明管花肉苁蓉苯乙醇苷改善脂质异位沉积。
为进一步观察管花肉苁蓉苯乙醇苷对HFD小鼠脂质异位沉积的影响,对肝脏组织切片进行H&E染色。结果如图6-F所示,NFD组肝细胞结构清晰,无明显变性;HFD组出现空泡,主要为大型空泡,出现明显缝隙,说明 HFD组出现明显脂肪变性;与HFD组相比,管花肉苁蓉苯乙醇苷减少了组织切片中空泡的数量。同时,管花肉苁蓉苯乙醇苷减少了HFD小鼠肝组织中TG和TC含量(图6-G和H)。
AMPK是控制肝细胞内脂质代谢的主要介质,包括肝脏中脂肪酸的摄取,合成和氧化。因此,通过WB检测了肝组织AMPKα总蛋白表达量及其苏氨酸172位的磷酸化水平;管花肉苁蓉苯乙醇苷对AMPKα的表达没有明显影响,而管花肉苁蓉苯乙醇苷给药组明显增加了AMPKα(Thr-172)的磷酸化水平(图6-I);以上结果提示管花肉苁蓉苯乙醇苷可能通过促进肝脏中 AMPK的激活来抑制肝脏脂肪变性。
实施例7管花肉苁蓉苯乙醇苷对HFD小鼠其他器官的影响
根据脏器指数统计后发现,管花肉苁蓉苯乙醇苷给药后HFD小鼠的心脏、肺、肾脏指数与模型组相比均无显著差异(表1),管花肉苁蓉苯乙醇苷给药可显著恢复脾脏指数,说明管花肉苁蓉苯乙醇苷在本实验剂量范围内是相对安全的。
表1
NFD | HFD | MET | 管花肉苁蓉苯乙醇苷 | |
脾脏 | 0.8±1.04 | 0.46±0.04 | 0.42±0.05 | 0.66±0.07* |
心脏 | 0.70±0.05 | 0.55±0.05 | 0.63±0.06 | 0.60±0.04 |
肾脏 | 1.38±0.04 | 1.16±0.09 | 1.32±0.05 | 1.30±0.06 |
肺 | 0.83±0.03 | 0.67±0.10 | 0.63±0.02 | 0.69±0.09 |
实施例8管花肉苁蓉苯乙醇苷通过调节IRS1/Akt信号通路改善HFD 小鼠的胰岛素抵抗
HFD小鼠的IR伴随高胰岛素血症和高血糖症。为进一步考察管花肉苁蓉苯乙醇苷对HFD肥胖小鼠IR的影响,检测小鼠血糖和胰岛素水平,并计算胰岛素抵抗指数进一步确定管花肉苁蓉苯乙醇苷对IR的改善作用。结果如图7-A-C所示,HFD组血糖水平和胰岛素水平显著高于NFD组;与HFD 组相比,管花肉苁蓉苯乙醇苷给药组显著降低了小鼠随机血糖、空腹血糖和空腹胰岛素水平;管花肉苁蓉苯乙醇苷给药组小鼠空腹血糖和空腹胰岛素水平分别降低了44.5%和25.6%,而MET组分别降低了13.7%和17.4% (P<0.05)。通过计算HOMA2-IR、HOMA2-%B、HOMA2-%S指数发现,与HFD组相比,管花肉苁蓉苯乙醇苷给药组同MET组显著降低了HOMA2-IR,增加了HOMA2-%S(P<0.05),而对HOMA2-%B有增加的趋势(图7-D-F)。以上结果表明,管花肉苁蓉苯乙醇苷显著改善小鼠IR。
为明确管花肉苁蓉苯乙醇苷改善HFD小鼠IR的作用机制,取各组小鼠 eWAT进行Western Blot实验检测胰岛素信号分子蛋白水平。结果如图7-G 所示,管花肉苁蓉苯乙醇苷给药组增加eWAT Akt 473位丝氨酸(Ser 473) 位点和Akt 308位苏氨酸(Thr 308)的磷酸化,并促进GLUT4的表达;灰度扫描结果显示,管花肉苁蓉苯乙醇苷给药组增加pAktthr308/Akt比值,显著增加pAkt ser473/Akt和pIRS1/IRS1比值,升高GLUT4表达(P<0.05)(图 7-H-K)。结果表明,管花肉苁蓉苯乙醇苷通过调节IRS1/Akt增强HFD小鼠脂肪胰岛素敏感性,进而改善小鼠机体IR。
实施例9管花肉苁蓉苯乙醇苷有效改善HFD小鼠肠道微生物组成、结构重塑和功能
组间基因数目差如图8-A所示,HFD组基因数目显著低于NFD组,说明HFD小鼠肠道微生物基因数会显著减小;但经管花肉苁蓉苯乙醇苷灌胃治疗给药后,小鼠肠道基因数量有所增加,可与正常组水平相一致。同时统计分析各处理组门水平上物种的相对丰度,结果如图8-B所示,各组的肠道微生物不同菌门占比不同,其中最主要的肠道菌门有:厚壁菌门(Fimicutes)、拟杆菌门(Bacteroidetes)和变形菌门(Proteobacteria)三种。与NFD组相比,HFD组中变形菌门(Proteobacteria),脱铁杆菌门(Deferribacteres)和螺旋菌门(Spirochaetes)相对丰度明显增加,而拟杆菌门(Bacteroidetes) 相对丰度减少。与HFD组相比,管花肉苁蓉苯乙醇苷给药组明显减少了变形菌门(Proteobacteria)、脱铁杆菌门(Deferribacteres)和螺旋菌门 (Spirochaetes)相对丰度。
进一步观察管花肉苁蓉苯乙醇苷对HFD喂养的小鼠肠道微生物组成的影响,对于组间具有差异的35个物种进行丰度聚类热图分析。结果如图8-C 所示,35个具有显著差异的物种如包氏梭菌(Clostridium populeti)、拟杆菌 CAG545(Bacteroides sp.CAG545)、拟杆菌CAG709(Bacteroides sp.CAG709)、多尔氏菌CAG105(Dorea sp.CAG105)、杆菌An23(Cloacibacillus sp.An23)、口腔脱硫微菌(Desulfomicrobium orale)和普通脱硫弧菌(Desulfovibrio vulgaris)等在管花肉苁蓉苯乙醇苷给药组中丰度跟NFD组相似,表明管花肉苁蓉苯乙醇苷给药恢复了以上16个物种的丰度。
为了揭示管花肉苁蓉苯乙醇苷对小鼠肠道微生物结构的影响,基于 Bray-Curtis距离进行了主坐标分析(PCoA,Principal Co-ordinates Analysis),结果如图8-D所示,NFD和管花肉苁蓉苯乙醇苷组不同样品距离较为接近,且与HFD距离较远,说明其肠道微生物种类较为类似。实验结果说明管花肉苁蓉苯乙醇苷给药对HFD诱导的肥胖小鼠肠道菌群结构有所调节,使其更接近于NFD组肠道微生物结构。
同时,基于Bray-Curtis距离构建样品的聚类树进行聚类分析,结果如图 8-E所示,NFD和HFD、管花肉苁蓉苯乙醇苷在此树状图中明显地分为两个分支,NFD组的三个样本与其他组的样本不在同一聚类分支上。管花肉苁蓉苯乙醇苷给药组与HFD组也不在同一个分支上,相似度出现明显的差异,表明管花肉苁蓉苯乙醇苷给药改变HFD肠道菌群结构,此结果与PCoA分析结果相一致。
此外,根据组间具有差异的功能绘制丰度聚类热图,结果如图8-F所示,具有显著差异的35个功能(酶)在这三组之间的丰度分布明显不同。其中, K00661(麦芽糖O-乙酰转移酶)、K07483(转座酶)、K01190(β-半乳糖苷酶)、K19310(杆菌肽转运系统通透性蛋白)、K19309(杆菌肽转运系统ATP 结合蛋白)在HFD组丰度明显低于NFD组,其他差异功能酶在HFD组中明显高于NFD组。而管花肉苁蓉苯乙醇苷给药组明显恢复了K00789(腺苷甲硫氨酸合成酶),K02519(翻译起始因子IF-2),K03043(DNA指导的RNA 聚合酶β亚单位),K02881(大亚基核糖体蛋白L18),K02876(大亚基核糖体蛋白L15),K02355(延伸因子G),K00826(支链氨基酸转氨酶),K03768 (肽基脯氨酰顺反异构酶B(亲环素B)),K00640(丝氨酸O-乙酰转移酶), K02469(DNA旋转酶亚单位A),K02470(DNA旋转酶亚单位B)的丰度;其中支链氨基酸转氨酶跟氨基酸代谢相关,在肥胖、胰岛素抵抗和糖尿病中起着重要作用。
由以上实施例可知,本发明提供了苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用。本发明确定管花肉苁蓉苯乙醇苷对鼠源 3T3-L1前脂肪细胞分化及脂质积累具有明显抑制作用,并显著改善高脂饮食诱导的肥胖小鼠胰岛素抵抗,可用于制备抗肥胖相关糖尿病药物。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (2)
1.苯乙醇苷在制备抗肥胖相关糖尿病药物或调节肠道菌群药物中的应用。
2.根据权利要求1所述的应用,其特征在于,所述来源于管花肉苁蓉。
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