摘要
目的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 To explore the mechanism of Cirsium japonicum extract in improving hypercholesterolemia based on metabolomics technology.METHODS 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 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 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.
作者
高梦梦
陈桢琳
郝雅坤
郭姣
GAO Mengmeng;CHEN Zhenlin;HAO Yakun;GUO Jiao(Institute of Traditional Chinese Medicine/Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine/Key Laboratory of Glucolipid Metabolism Disease/Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Metabolic Diseases of Guangdong Province,Guangdong Pharmaceutical University,Guangzhou 510006,China;College of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou,510006,China)
出处
《中国药房》
CAS
北大核心
2023年第13期1590-1595,共6页
China Pharmacy
基金
广东省基础与应用基础研究重大项目(No.2019B-030302005)。
关键词
大蓟提取物
代谢组学
高胆固醇血症
代谢通路
Cirsium japonicum extract
metabolomics
hypercholesterolemia
metabolism pathway
