CN114177164B - 白花败酱蒽醇i的制备方法及其应用 - Google Patents
白花败酱蒽醇i的制备方法及其应用 Download PDFInfo
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- 235000019109 Patrinia villosa Nutrition 0.000 title claims abstract description 38
- MUVQKFGNPGZBII-UHFFFAOYSA-N 1-anthrol Chemical compound C1=CC=C2C=C3C(O)=CC=CC3=CC2=C1 MUVQKFGNPGZBII-UHFFFAOYSA-N 0.000 title claims description 17
- 244000148137 Patrinia villosa Species 0.000 title abstract description 32
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 241000606264 Patrinia Species 0.000 claims abstract description 6
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- 239000004480 active ingredient Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 14
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 abstract description 14
- 102100024295 Maltase-glucoamylase Human genes 0.000 abstract description 11
- 108010028144 alpha-Glucosidases Proteins 0.000 abstract description 11
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- IFBHRQDFSNCLOZ-IIRVCBMXSA-N 4-nitrophenyl-α-d-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 IFBHRQDFSNCLOZ-IIRVCBMXSA-N 0.000 description 2
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 2
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- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
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- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
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- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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Abstract
本发明涉及白花败酱蒽醇I的制备方法及其应用,将白花败酱草全草粉碎后乙醇回流提取,减压浓缩得到浸膏;用等体积的石油醚、二氯甲烷和正丁醇依次萃取;将二氯甲烷层经硅胶柱层析色谱分离,得到Fr.1~Fr.10共10个组分;其中Fr.5经ODS柱层析色谱进一步分离,用甲醇‑水梯度洗脱得到Fr.5‑1~Fr.5‑5共5个组分;其中Fr.5‑4经Sephadex LH‑20柱层析色谱分离,后并经半制备高效液相色谱法纯化后得到白花败酱蒽醇I。本发明研究表明白花败酱蒽醇I的提取方法简单,适合大规模生产,白花败酱蒽醇I能够抑制α‑葡萄糖苷酶、可作为制备降血糖药物药物的应用。
Description
技术领域
本发明属于医药技术领域,具体为白花败酱蒽醇I的制备方法及其应用。
背景技术
白花败酱草,又名萌菜、胭脂麻、苦斋等,为败酱属植物白花败酱Patriniavillosa(Thunb.)Juss.的干燥全草,广泛分布于亚洲东部和北美洲。白花败酱是一种多年生草本植物,最早记载于《神农本草经》。其味苦,性寒,无毒。在民间,白花败酱草也被作为一种野菜食用,属于历史悠久的药食同源植物。白花败酱草作为草药有着悠久的药用历史,具有散瘀消肿、活血排脓的作用,主要用于治疗阑尾炎、痢疾、肝炎、扁桃体炎、结肠炎等。现代研究表明,白花败酱草富含苯丙酸类、黄酮类、萜类、皂苷类等多种生物活性成分,具有多种药理活性。
我们从白花败酱草Patrinia villosa(Thunb.)Juss.70%乙醇提取物中采用各种色谱方法分离得到了白花败酱蒽醇I,前期药效研究发现白花败酱蒽醇I能够抑制α-葡萄糖苷酶、降低血糖浓度,对于防治2型糖尿病具有较好效果。
发明内容
本发明的目的在于提供白花败酱蒽醇I的制备方法及其应用。
本发明的技术方案概述如下:
白花败酱蒽醇I在制备防治2型糖尿病药物中的应用,白花败酱蒽醇I的结构式如式(I)所示:
白花败酱蒽醇I的制备方法如下:
(1)提取:干燥的白花败酱草全草粉碎后以6倍体积的70%乙醇回流提取3次,每次提取2h。合并提取液后干燥并减压浓缩得到浸膏。
(2)分离:适量蒸馏水充分溶解浸膏后,用等体积的石油醚、二氯甲烷和正丁醇依次萃取。将二氯甲烷层经硅胶柱层析色谱分离,用二氯甲烷-甲醇(100:1→1:1)梯度洗脱得到Fr.1~Fr.10共10个组分。其中Fr.5经ODS柱层析色谱进一步分离,用甲醇-水(10%~100%)梯度洗脱得到Fr.5-1~Fr.5-5共5个组分。其中Fr.5-4经Sephadex LH-20柱层析色谱分离,用70%甲醇等度洗脱并经半制备高效液相色谱法纯化后得到白花败酱蒽醇I。
本发明还提供了白花败酱蒽醇I在制备α-葡萄糖苷酶抑制剂中的应用。
本发明还提供了白花败酱蒽醇I在制备降低血糖的保健食品或药物中的应用。
白花败酱蒽醇I为黄色固体(甲醇)。高分辨电喷雾电离质谱HR-ESI-MS(图6)显示在m/z 451.2854[m-H]-处有一个准分子离子峰(计算值C29H39O4,m/z 451.2852[m-H]-),提示化合物1的分子式为C29H40O4。
1H-NMR和13C-NMR数据见表1。
表1化合物1的13C-NMR和1H-NMR谱数据(DMSO-d6,δin ppm)
Table 1 13C-NMR and 1H-NMR data of Compound 1 in DMSO-d6(δin ppm)
白花败酱蒽醇I结构解析:
如图1-6所示,白花败酱蒽醇I的1H NMR、13C NMR、2D-NMR(HSQC、HMBC)谱,以及HR-ESI-MS谱得知化合物结构。具体地说:
化合物1为黄色固体(甲醇)。高分辨电喷雾电离质谱(HR-ESI-MS)显示在m/z451.2854[m-H]-处有一个准分子离子峰(计算值C29H39O4,m/z451.2852[m-H]-),提示化合物1的分子式为C29H40O4。化合物1的1H-NMR、13C-NMR和HSQC光谱数据显示存在29个碳信号,包括1个甲基(δC 13.8)、1个甲氧基(δC 49.6)、13个亚甲基(δC 35.0、25.0、29.0、28.9、28.8、28.7、28.7、28.6、28.5、28.5、28.4、31.2和22.0)、5个芳香甲基(δC 116.5、127.9、119.3、128.8和128.6),9个芳香族季碳(δC 152.9,121.8,166.5,131.3,130.5,154.7,133.1,161.0和134.6)。化合物1的1H-NMR谱表明,δH 7.61(1H,dd,J=1.2,7.8Hz,H-2)、7.40(1H,dd,J=7.8,7.8Hz,H-3)和7.30(1H,dd,J=1.2,7.8Hz,H-4)提示在结构中存在ABC耦合系统;δH 7.78(1H,dd,J=1.2,7.8Hz,H-8)和7.58(1H,d,J=7.8Hz,H-9)提示在苯环上的存在邻位耦合系统。化合物1的13C-NMR谱中,碳信号主要集中在两个区域中,即高场区的脂肪碳信号特征区和低场区的芳香碳信号特征区,其中高场区的碳信号表明化合物中可能存在链状脂肪烃结构。在13C-NMR的高场区,有9个碳信号δC 29.0(C-3’)、28.9(C-4’)、28.8(C-5’)、28.7(C-6’)、28.7(C-7’)、28.6(C-8’)、28.5(C-9’)、28.5(C-10’)、28.4(C-11’),与上述碳信号相关的氢信号均出现在相近的化学位移处,相互重叠形成高响应值的氢信号峰,表明与这9个碳原子相连的氢原子都处于非常相似的化学环境中,提示该化合物中存在-(CH2)9-的链状结构。在13C-NMR谱的低场区有14个芳香碳信号,表明化合物中存在蒽结构,较大的化学位移表明碳原子与氧原子相连。化学位移值在δC 49.6(-OMe)处的碳原子信号为甲氧基上的碳原子信号。结合1H-NMR谱提供的氢信号信息,可以确定母核结构中有5个碳原子与取代基相连。进一步分析HSQC谱中的相关信息,可以将一个含有14个碳原子的脂肪烃链连接起来,即-CH2-CH2-(CH2)9-CH2-CH2-CH3。
在HMBC谱中,δH 7.78(1H,dd,J=1.2,7.8Hz,H-8)与δC 130.5(C-10)、133.1(C-12)、166.6(C-6)相关、δH 7.61(1H,dd,J=1.2,7.8Hz,H-2)和δC 128.8(C-8)、133.1(C-12)相关、δH 7.58(1H,d,J=7.8Hz,H-9)和δC 131.3(C-7)相关、δH 7.40(1H,dd,J=7.8,7.8Hz,H-3)和δC 121.8(C-5)、152.9(C-1)相关、δH 7.30(1H,dd,J=1.2,7.8Hz,H-4)和δC 116.5(C-2),134.6(C-14),152.9(C-1)相关,以上数据有助于确定蒽环母核上取代基的位置和碳信号的归属。δH 4.29(3H,s,-OMe)和δC 154.7(C-11)的相关性表明甲氧基取代基的位置。综合以上信息,化合物的分子结构可以得到确定,命名为8-甲氧基-7-n-十四烷基-1,9,10-蒽三醇。经文献检索未发现报道,鉴定为新化合物。该化合物重要的1H-1H COSY和HMBC关联如图4、5所示,13C-NMR和1H-NMR的信号归属如表1所示。
本发明的有益效果:
本研究证明白花败酱蒽醇I的提取方法简单,适合大规模生产,白花败酱蒽醇I能够抑制α-葡萄糖苷酶、可作为制备降血糖药物药物的应用。
附图说明
图1白花败酱蒽醇I的1H NMR谱;
图2白花败酱蒽醇I的13C NMR谱;
图3白花败酱蒽醇I的HSQC谱;
图4白花败酱蒽醇I的HMBC谱;
图5白花败酱蒽醇I的COSY谱;
图6白花败酱蒽醇I的HR-ESI-MS谱。
具体实施方式
下面通过实施例进一步描述本发明,使本专业技术更全面地理解本发明,但不以任何方式限制本发明。
实施例1
白花败酱蒽醇I的制备方法
(1)提取:干燥的白花败酱草全草(15kg)粉碎后以6倍体积的70%乙醇回流提取3次,每次提取2h。合并提取液后干燥并减压浓缩得到约2.8kg浸膏。
(2)分离:适量蒸馏水充分溶解浸膏后,用等体积的石油醚、二氯甲烷和正丁醇依次萃取。将二氯甲烷层(110g)经硅胶柱层析色谱分离,用二氯甲烷-甲醇(100:1→1:1)梯度洗脱得到Fr.1~Fr.10共10个组分。其中Fr.5经ODS柱层析色谱进一步分离,用甲醇-水(10%~100%)梯度洗脱得到Fr.5-1~Fr.5-5共5个组分。其中Fr.5-4经Sephadex LH-20柱层析色谱分离,用70%甲醇等度洗脱并经半制备高效液相色谱法纯化后得到白花败酱蒽醇I(19.9mg)。
实施例2
白花败酱蒽醇I对α-葡萄糖苷酶的抑制作用研究
α-葡萄糖苷酶在食物吸收过程中起着重要的作用,必须与之结合后,食物才能消化和吸收。α-葡萄糖苷酶抑制剂的降糖机制是,通过抑制肠黏膜上的α-葡萄糖苷酶,使淀粉分解为葡萄糖的速度减缓,减少和延缓小肠对葡萄糖的吸收,以降低血糖,对餐后高血糖的作用比较明显。葡萄糖苷酶抑制剂不刺激胰岛素的分泌,单独使用本类药物通常不会引发低血糖,因此可帮助减少血糖的波动。可以明显降低糖尿病患者发生心血管病变的概率,对心肌梗死的改善作用最为显著。
1.1仪器与试药
紫外-可见分光光度计购于上海尤尼柯仪器有限公司;α-葡萄糖苷酶,4-硝基酚α-D-吡喃葡萄糖苷(PNPG)购于Sigma公司;阿卡波糖购于拜尔医药保健有限公司;还原型谷胱苷肽购于北京欣经科生物技术有限公司。
1.2实验方法
1.2.1试剂配制
白花败酱蒽醇I以含有0.05%二甲基亚砜的磷酸钾缓冲液为溶剂溶解,制成标准品溶液;α-葡萄糖苷酶冻干粉用纯净水稀释溶解(0.8U/mL);PNPG干粉溶于纯净水中(50mmol/L);还原型谷胱甘肽(2mg/mL);Na2CO3(0.1mol/L)。
1.2.2阳性对照品溶液的配制
取阿卡波糖(100mg)研碎,加蒸馏水10mL,37℃溶解、过滤、取上清液20μL(浓度为0.5μM、1μM、2μM、4μM、8μM)。
1.2.3α-葡萄糖苷酶抑制活性评价:
试管中分别加入850μL磷酸钾缓冲液(67mmol/L),20μL不同浓度待测样品(2.5μM、5μM、10μM、15μM、20μM),35μLα-葡萄糖苷酶(0.8U/mL),25μL还原型谷胱苷肽,试管于37℃恒温孵育10min,加入70μLPNPG(50mmol/L),37℃恒温孵育20min,以Na2CO3(5mL)终止反应,于400nm下测吸光度值,计算IC50值:
抑制率(%)=(空白对照组OD值—给药组OD值)/空白对照组OD值×100%。
结果显示白花败酱蒽醇I对α-葡萄糖苷酶有显著抑制作用,呈一定量效关系,IC50值为13.2μM,阳性对照组阿卡波糖IC50值为1.48μM。
尽管本发明的实施方案已公开如上,但其并不仅仅限于说明书和实施方式中所列运用,它完全可以被适用于各种适合本发明的领域,对于熟悉本领域的人员而言,可容易地实现另外的修改,因此在不背离权利要求及等同范围所限定的一般概念下,本发明并不限于特定的细节。
Claims (1)
1.白花败酱蒽醇I作为唯一活性成分在制备防治2型糖尿病药物中的应用,白花败酱蒽醇I的结构式如式(I)所示:
(I)。
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CN109180471A (zh) * | 2018-08-17 | 2019-01-11 | 河南中医药大学 | 水栀子单萜类化合物crocusatinN和jasminosideB制备方法及应用 |
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