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1.广东药科大学中医药研究院/广东省代谢病中西医结合研究中心/糖脂代谢病教育部重点实验室/广东省代谢性疾病中医药防治重点实验室,广州 510006
2.广东药科大学中药学院,广州 510006
Published:15 July 2023,
Received:10 February 2023,
Revised:09 May 2023,
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高梦梦,陈桢琳,郝雅坤等.大蓟提取物改善高胆固醇血症模型小鼠的代谢组学研究 Δ[J].中国药房,2023,34(13):1590-1595.
GAO Mengmeng,CHEN Zhenlin,HAO Yakun,et al.Metabolomics study on improvement effects of Cirsium japonicum extract on hypercholesterolemia model mice[J].ZHONGGUO YAOFANG,2023,34(13):1590-1595.
高梦梦,陈桢琳,郝雅坤等.大蓟提取物改善高胆固醇血症模型小鼠的代谢组学研究 Δ[J].中国药房,2023,34(13):1590-1595. DOI: 10.6039/j.issn.1001-0408.2023.13.09.
GAO Mengmeng,CHEN Zhenlin,HAO Yakun,et al.Metabolomics study on improvement effects of Cirsium japonicum extract on hypercholesterolemia model mice[J].ZHONGGUO YAOFANG,2023,34(13):1590-1595. DOI: 10.6039/j.issn.1001-0408.2023.13.09.
目的
2
基于代谢组学技术探究大蓟提取物改善高胆固醇血症的作用机制。
方法
2
以大孔树脂吸附法制备大蓟提取物,并利用液相色谱-质谱联用仪鉴定其主要成分。实验小鼠先随机分为对照组(
n
=6)和造模组(
n
=16),造模组小鼠采用饮食诱导建立高胆固醇血症模型,造模成功后,再将造模组小鼠分为模型组(
n
=8)及大蓟提取物组(
n
=8)。大蓟提取物组小鼠灌胃大蓟提取物400 mg/(kg·d)(以提取物计),其余2组小鼠灌胃等体积0.3%羧甲基纤维素钠溶液,持续6周。给药结束后,以血清总胆固醇(TC)、甘油三酯(TG)水平和肝脏组织病理变化评价大蓟提取物的干预效果,并通过代谢组学方法探讨大蓟提取物改善高胆固醇血症模型小鼠的相关机制。
结果
2
从大蓟提取物中共鉴定出绿原酸、蒙花苷、柳穿鱼叶苷等12种成分。给药6周后,与对照组比较,模型组小鼠血清中TC水平显著升高、TG水平显著降低(
P
<0.05),肝脏组织出现大量脂滴,肝细胞排列紊乱,肝索结构被破坏。与模型组比较,大蓟提取物组小鼠血清中TC水平显著下降(
P
<0.05);肝脏组织中的脂滴明显减少,肝细胞以中央静脉为中心呈放射状紧密排列,肝索排列整齐。代谢组学研究显示,大蓟提取物干预后,乙醇胺、富马酸、胆固醇等代谢产物水平发生显著回调;最终得到丙氨酸-天冬氨酸-谷氨酸代谢、精氨酸生物合成、柠檬酸循环3条代谢通路。
结论
2
大蓟提取物的成分主要是酚酸类和黄酮类,如绿原酸、蒙花苷、柳穿鱼叶苷等;大蓟提取物可能通过调节差异代谢物的含量及分布,以及调节丙氨酸-天冬氨酸-谷氨酸代谢、精氨酸生物合成、柠檬酸循环3条主要的差异代谢通路,参与氧化还原反应、改善肝脏脂质蓄积、发挥抗炎作用,从而改善高胆固醇血症。
OBJECTIVE
2
To explore the mechanism of
Cirsium japonicum
extract in improving hypercholesterolemia based on metabolomics technology.
METHODS
2
The extract of
C. japonicum
was prepared by macroporous resin adsorption, and its main components were identified by liquid chromatography-tandem mass spectrometry. The experimental mice were randomly divided into control group (
n
=6) and modeling group (
n
=16). The hypercholesterolemia model was induced by diet in modeling group; after modeling, the rats of modeling group were divided into model group (
n
=8) and
C. japonicum
extract group (
n
=8).
C. japonicum
extract group was given
C. japonicum
extract 400 mg/(kg·d) by gavage (calculated by extract), and other 2 groups were given constant volume of 0.3% sodium carboxymethyl cellulose solution, for 6 weeks. After medication, the intervention effect of
C. japonicum
extract was evaluated by the levels of serum total cholesterol (TC), triglyceride (TG) and the histopathological changes of liver. The mechanism of
C. japonicum
extract in improving hypercholesterolemia model mice was investigated by metabolomics.
RESULTS
2
It was identified that
C. japonicum
extract contained 12 components, such as chlorogenic acid, linarin and pectolinarin. After 6 weeks of intervention, compared with control group, serum level of TC was increased significantly while the level of TG was decreased significantly in model group (
P
<0.05), while a large number of lipid droplets, disorderly arrangement of liver cells and the damaged structure of liver cord were observed in liver tissue. Compared with model group, the serum level of TC was decreased significantly in
C. japonicum
extract group(
P
<0.05); the lipid droplets in liver tissue were significantly reduced, with liver cells arranged radially and tightly centered around the central vein, and liver cords arranged neatly. The metabolomics study showed that after the intervention of
C. japonicum
extract, the levels of metabolites were significantly adjusted back, such as ethanolamine, fumaric acid and cholesterol; finally, three metabolism pathways, such as alanine-aspartate-glutamic acid metabolism, arginine biosynthesis, citric acid cycle, were obtained.
CONCLUSIONS
2
The main components of
C. japonicum
extract are phenolic acids and flavonoids, such as chlorogenic acid, linarin, pectolinarin.
C. japonicum
extract can improve hypercholesterolemia by regulating the contents and distribution of differential metabolites, adjusting alanine-aspartate-glutamic acid metabolism, arginine biosynthesis and citric acid cycle, participating in oxidation-reduction reaction, improving liver lipid accumulation, and playing anti-inflammatory role.
大蓟提取物代谢组学高胆固醇血症代谢通路
metabolomicshypercholesterolemiametabolism pathway
诸骏仁,高润霖,赵水平,等. 中国成人血脂异常防治指南:2016年修订版[J]. 中华心血管病杂志,2016,44(10):833-853.
XU D Y,SHU J,HUANG Q Y,et al. Evaluation of the lipid lowering ability,anti-inflammatory effects and clinical safety of intensive therapy with Zhibitai,a Chinese traditional medicine[J]. Atherosclerosis,2010,211(1):237-241.
GUO J,BEI W J,HU Y M,et al. A new TCM formula FTZ lowers serum cholesterol by regulating HMG-CoA reductase and CYP7A1 in hyperlipidemic rats[J]. J Ethnopharmacol,2011,135(2):299-307.
田时秋,李依林,裴海鸾,等. 高脂血症发病机制及药物治疗[J]. 生命的化学,2022,42(12):2237-2247.
国家药典委员会. 中华人民共和国药典:一部[M]. 北京:中国医药科技出版社,2020:26.
CHE D N,SHIN J Y,KANG H J,et al. Ameliorative effects of Cirsium japonicum extract and main component cirsimaritin in mice model of high-fat diet-induced metabolic dysfunction-associated fatty liver disease[J]. Food Sci Nutr,2021,9(11):6060-6068.
马勤. 大蓟化学成分及其黄酮类化合物的生物活性研究[D].广州:华南理工大学,2019.
SUN Q,CHANG L,REN Y,et al. Simultaneous analysis of 11 main active components in Cirsium setosum based on HPLC-ESI-MS/MS and combined with statistical methods[J]. J Sep Sci,2012,35(21):2897-2907.
LI K P,YUAN M,HE Z R,et al. Omics insights into metabolic stress and resilience of rats in response to short-term fructose overfeeding[J]. Mol Nutr Food Res,2019,63(23):e1900773.
王振平,毕佳,陈忠科. 大蓟水煎剂治疗小鼠高血压的研究[J]. 山东大学学报(理学版),2011,46(7):7-10.
YE Y,CHEN Z,WU Y,et al. Purification process and in vitro and in vivo bioactivity evaluation of pectolinarin and linarin from Cirsium japonicum[J]. Molecules,2022,27(24):8695-8707.
王泽琨,刘沈林,于小聪,等. 基于血清代谢组学探讨复方枣仁颗粒改善失眠的机制[J]. 中国药房,2023,34(9):1093-1098.
武宇佳,万浩芳,李畅,等. 基于HPLC-Q-exactive液质联用技术与HPLC的通脉降糖胶囊成分分析及指纹图谱研究[J]. 中草药,2022,53(21):6686-6697.
陈玮玲,钟培培,王远兴. 青钱柳叶活性成分的抗氧化活性及UPLC-QTOF-MS/MS分析[J]. 食品科学,2017,38(8):122-128.
兰晓燕,朱龙波,黄显章,等. 艾叶中主要化学成分的鉴定及其含量测定研究[J]. 中草药,2021,52(24):7630-7637.
孙倩. 基于液质联用技术的大小蓟多组分分析与黄酮类成分的药物代谢动力学研究[D].石家庄:河北医科大学,2013.
丁健桦,王兴祥,张慧,等. 芹菜素的电喷雾萃取电离串联质谱[J]. 高等学校化学学报,2011,32(8):1714-1719.
鲍和,张昌龙,苏娅萍,等. 高脂饮食诱导建立小鼠高脂血症模型[J]. 西北药学杂志,2019,34(1):47-51.
AKRAM M. Citric acid cycle and role of its intermediates in metabolism[J]. Cell Biochem Biophys,2014,68(3):475-478.
SONG S,HAN Y,ZHANG Y,et al. Protective role of ci- tric acid against oxidative stress induced by heavy metals in Caenorhabditis elegans[J]. Environ Sci Pollut Res Int,2019,26(36):36820-36831.
ROH K B,JUNG E,PARK D,et al. Fumaric acid attenuates the eotaxin-1 expression in TNF-alpha-stimulated fibroblasts by suppressing p38 MAPK-dependent NF-κB signaling[J]. Food Chem Toxicol,2013,58:423-431.
KAUR G,SHIVANANDAPPA T B,KUMAR M,et al. Fumaric acid protect the cadmium-induced hepatotoxicity in rats:owing to its antioxidant,anti-inflammatory action and aid in recast the liver function[J]. Naunyn Schmiedebergs Arch Pharmacol,2020,393(10):1911-1920.
ROWLEY C A,ANDERSON C J,KENDALL M M. Ethanolamine influences human commensal Escherichia coli growth,gene expression,and competition with enterohemorrhagic E. coli O157∶H7[J]. mBio,2018,9(5):e01429-e01418.
ZENG M,LIANG Y,LI H,et al. Plasma metabolic fingerprinting of childhood obesity by GC/MS in conjunction with multivariate statistical analysis[J]. J Pharm Biomed Anal,2010,52(2):265-272.
KALVEGREN H,BYLIN H,LEANDERSON P,et al. Chlamydia pneumoniae induces nitric oxide synthase and lipoxygenase-dependent production of reactive oxygen species in platelets. Effects on oxidation of low density lipoproteins[J]. Thromb Haemost,2005,94(2):327-335.
INOUE S,OKITA Y,DE TOLEDO A,et al. Pyroglutamic acid stimulates DNA synthesis in rat primary hepatocytes through the mitogen-activated protein kinase pathway[J]. Biosci Biotechnol Biochem,2015,79(5):795-798.
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