铁轴草化学成分及其对HT-22细胞铁死亡抑制活性研究

Constituents from Teucrium quadrifarium and its HT-22 cells ferroptosis inhibitory activity

目的研究铁轴草Teucrium quadrifarium化学成分及其生物活性。方法采用硅胶柱色谱、Sephadex LH-20柱色谱、半制备高效液相色谱以及重结晶等方法对铁轴草乙醇提取物的石油醚部位进行了系统分离纯化,并利用现代波谱技术对分离得到的单体化合物进行结构鉴定;采用MTT法评估单体化合物对RSL3诱导的HT-22细胞铁死亡抑制活性。结果从铁轴草石油醚部位共分离得到16个化合物,分别鉴定为(4R,5S,7R)-木萝烷-1(6),10(14)-二烯-4,5-二醇(1)、对甲磺酰甲基苯酚(2)、合欢金素(3)、6,4′-二甲氧基-野黄芩苷(4)、香叶木素(5)、去甲氧基矢车菊黄酮素(6)、5-羟基-3,3′,4′,5′,7-五甲氧基黄酮(7)、蓟黄素(8)、吲哚-3-甲酸乙酯(9)、13-酮-9,11-十八碳二烯酸(10)、9-酮-10,12-十八碳二烯酸(11)、α-托可醌(12)、N-苯甲酰-L-苯丙氨酰-N-苯甲酰-L-苯丙氨酸酯(13)、金色酰胺醇酯(14)、2″,3″-乙酰马蒂罗苷(15)、香草醛(16)。活性筛选结果显示化合物7、9可以抑制铁死亡诱导剂RSL3诱导的HT-22细胞铁死亡,半数效应浓度(median effect concentration,EC50)分别为(1.46±0.49)μmol/L和(3.31±1.66)μmol/L。结论化合物1是新的倍半萜类化合物,命名为铁轴草素A;化合物2、4、6、7、9~16为首次从该属植物中分离得到。该研究结果为深入开发利用该植物提供一定的科学依据。

Obiective To investigate the chemical constituents of Teucrium quadrifarium and their bioactivities.Methods The petroleum ether part of ethanol extracts of T.quadrifarium has been separated and purified by silica gel chromatography,Sephadex LH-20 gel column chromatography,semi-preparative high performance liquid chromatography,and recrystallization methods,respectively.The chemical structures were identified by modern spectroscopy identification.HT-22 cells ferroptosis inhibitory activity was evaluated by MTT method.Results Sixteen compounds were isolated and identified as(4R,5S,7R)-muurol-1(6),10(14)-diene-4,5-diol(1),p-methylsulfonylmethyl-phenol(2),acacetin(3),6,4′-dimethoxyl-scutellarin(4),diosmetin(5),demethoxycentaureidin(6),3,3′,4′,5′,7-penta-O-methylmyricetin(7),cirsimaritin(8),ethyl indole-3-carboxylate(9),(9Z,11E)-13-oxo-9,11-ocatadecadienoic acid(10),(E,E)-9-oxooctadeca-10,12-dienoic acid(11),α-tocopherolquinone(12),N-benzoyl-L-phenylalaninyl-N-benzoyl-L-phenylalaninate(13),aurantiamide acetate(14),2″,3″-O-acetylmartynoside(15),vanillin(16).Compounds 7 and 9 showed a remarkable inhibitory effect on RSL3⁃induced HT-22 cells ferroptosis,with EC50 values of(1.46±0.49)μmol/L and(3.31±1.66)μmol//L,respectively.Conclusion Compound 1 was a new sesquiterpene compound,named as terquadriol A.Compounds 2,4,6,7,and 9—16 were isolated from genus Teucrium for the first time.The results provide scientific basis for the development and utilization of T.quadrifarium.