基于~1H-NMR代谢组学的山楂不同炮制品对高脂血症大鼠模型的影响研究
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摘要
目的探讨山楂炒制前后调脂作用的差异,筛选山楂调脂最优炮制品。方法采用高脂饲料法制备SD大鼠高脂血症模型,应用1H-NMR测定大鼠血清代谢物,结合多元统计分析方法分析给予大鼠净山楂、炒山楂、焦山楂后血清代谢物的变化,比较各炮制品对高脂血症大鼠模型的干预作用。结果山楂不同炮制品均能显著降低高脂血症模型大鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平,其中净山楂降低血脂作用最佳。与对照组相比,模型组大鼠血清中乳酸、丙酮酸、赖氨酸、肌酸、甘油脂、鸟氨酸、氧化三甲胺(TMAO)、α-酮异戊酸、O-乙酰糖蛋白、N-乙酰糖蛋白、亮氨酸、异亮氨酸含量升高,而胆碱、丙酮、苏氨酸、鲨肌醇、谷氨酰胺、谷氨酸、单不饱和脂肪酸(MUFA)、多不饱和脂肪酸(PUFA)、甘油磷脂酰胆碱(GPC)、葡萄糖含量降低。给药后山楂各炮制组大鼠血清中内源性物质的代谢状态差异明显,与炒山楂、焦山楂组相比,净山楂组调节高脂血症模型大鼠血清中差异代谢物的数量和程度更接近对照组。结论山楂炮制后调脂作用存在差异,且以净山楂效果最优,可能是通过调节氧化应激、能量代谢、氨基酸代谢及肠道菌群等发挥作用。
Objective To investigate the difference of lipid-lowering effect of raw and processed Crataegi Fructus, and to select the optimal antihyperlipidemic product. Methods The hyperlipidemia model of SD rats was induced by high fat diet. After administration of Crataegi Fructus(1.5 g/kg), fried and coked Crataegi Fructus(1.5 g/kg), the changes of serum metabolites were analyzed by 1 H-NMR technique combined with multivariate statistical analysis. Results Different processing products of Crataegi Fructus can significantly reduce the levels of TC, TG, LDL-C in hyperlipidemia rats, among which Crataegi Fructus had best hypolipidemic effects. The serum contents of lactate, pyruvate, lysine, creatine, glycerol, ornithine, TMAO, α-ketoisovaleric acid, O-acetylglycoprotein,N-acetylglycoprotein, leucine and isoleucine were increased in model group, while choline, acetone, threonine, scyllitol, glutamine,glutamic acid, MUFA, PUFA, GPC, and glucose were decreased compared with control group. After administration of different processing products of Crataegi Fructus, endogenous metabolites were recovered significantly. The effect of Crataegi Fructus on hyperlipidemia was superior to those of fried and coked Crataegi Fructus according to the degree and number of the metabolites recovered. Conclusion There are differences between the raw and processed Crataegi Fructus, and raw Crataegi Fructus showed the best effect on hyperlipidemia, the effect may be achieved through regulating oxidative stress, energy metabolism, amino acid metabolism, and gut microbiota.
Objective To investigate the difference of lipid-lowering effect of raw and processed Crataegi Fructus, and to select the optimal antihyperlipidemic product. Methods The hyperlipidemia model of SD rats was induced by high fat diet. After administration of Crataegi Fructus(1.5 g/kg), fried and coked Crataegi Fructus(1.5 g/kg), the changes of serum metabolites were analyzed by 1 H-NMR technique combined with multivariate statistical analysis. Results Different processing products of Crataegi Fructus can significantly reduce the levels of TC, TG, LDL-C in hyperlipidemia rats, among which Crataegi Fructus had best hypolipidemic effects. The serum contents of lactate, pyruvate, lysine, creatine, glycerol, ornithine, TMAO, α-ketoisovaleric acid, O-acetylglycoprotein,N-acetylglycoprotein, leucine and isoleucine were increased in model group, while choline, acetone, threonine, scyllitol, glutamine,glutamic acid, MUFA, PUFA, GPC, and glucose were decreased compared with control group. After administration of different processing products of Crataegi Fructus, endogenous metabolites were recovered significantly. The effect of Crataegi Fructus on hyperlipidemia was superior to those of fried and coked Crataegi Fructus according to the degree and number of the metabolites recovered. Conclusion There are differences between the raw and processed Crataegi Fructus, and raw Crataegi Fructus showed the best effect on hyperlipidemia, the effect may be achieved through regulating oxidative stress, energy metabolism, amino acid metabolism, and gut microbiota.
引文
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[25]Holmes E,Li J V,Athanasiou T,et al.Understanding the role of gut microbiome-host metabolic signal disruption in health and disease[J].Trends Microbiol,2011,19(7):349-359.
[26]Jung J,Kim I Y,Kim Y N,et al.1H NMR-based metabolite profiling of diet-induced obesity in a mouse mode[J].Bmb Rep,2012,45(7):419-424.
[27]Sun Y,Zhang G,Hawkes C A,et al.Synthesis of scyllo-inositol derivatives and their effects on amyloid beta peptide aggregation[J].Bioorg Med Chem,2008,16(15):7177-7184.
[28]李贵海,孙敬勇,张希林,等.山楂降血脂有效成分的实验研究[J].中草药,2002,33(1):52-54.
[29]张良,姜思凡,万军,等.炮制对山楂主要化学成分的影响[J].长春中医药大学学报,2014,30(1):31-34.
[2]中国药典[S].一部.2015.
[3]李化,杨滨.山楂的炮制研究[J].中国中药杂志,2004,29(6):12-15.
[4]马传江,王信,辛义周,等.中药传统炮制理论的现代研究概述[J].中草药,2018,49(3):512-520.
[5]龚千峰.中药炮制学[M].北京:中国中医药出版社,2012.
[6]钟凌云,廖智慧,龚千锋,等.基于代谢组学研究姜制对黄连药性的影响[J].中草药,2013,44(22):3177-3181.
[7]Nicholson J K,Connelly J,Lindon J C,et al.Metabonomics:A platform for studying drug toxicity and genefunction[J].Nat Rev Drug Discov,2002,1(2):153-161.
[8]赵凡凡,李肖,高丽,等.甘草水提物干预D-半乳糖致衰老大鼠的肝脏代谢组学研究[J].中草药,2017,48(17):3545-3553.
[9]刘彩春,刘欢,谷陟欣,等.基于1H-NMR代谢组学的驴胶补血颗粒补血作用机制研究[J].中草药,2016,47(7):1142-1148.
[10]Oorni K,Pentikainen M O,Annila A,et al.Oxidation of low density lipoprotein particles decreases their ability to bind to human aortic proteoglycans:Dependence on oxidative modification of the lysine residues[J].J Biol Chem,1997,272(34):21303-21311.
[11]Al-Waiz M,Mikov M,Mitchell S C,et al.The exogenous origin of trimethylamine in the mouse[J].Metabolism,1992,41(2):135-136.
[12]Khatri J J,Johnson C,Magid R,et al.Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma[J].Circulation,2004,109(4):520-525.
[13]Browning J D,Horton J D.Molecular mediators of hepatic steatosis and liver injury[J].J Clin Invest,2004,114(2):147-152.
[14]Jiang C,Yang K,Yang L,et al.A 1H NMR-based metabonomic investigation of time-related metabolic trajectories of the plasma,urine and liver extracts of hyperlipidemic hamsters[J].PLoS One,2013,8(6):e66786.
[15]Araya J,Rodrigo R,Videla L A,et al.Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease[J].Clin Sci,2004,106(6):635-643.
[16]Martin J C,Canlet C,Delplanque B,et al.1H NMRmetabonomics can differentiate the early atherogenic effect of dairy products in hyperlipidemic hamsters[J].Atherosclerosis,2009,206(1):127-133.
[17]Ahmed N,Thornalley P J.Chromatographic assay of glycation adducts in human serum albumin glycated in vitro by derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and intrinsic fluorescence[J].Biochem J,2002,364(1):15-24.
[18]Guo W,Jiang C,Yang L,et al.Quantitative metabolomic profiling of plasma,urine and liver extracts by 1H NMRspectroscopy characterizes different stages of atherosclerosis in hamsters[J].J Proteome Res,2016,15(10):3500-3510.
[19]CataláA.A synopsis of the process of lipid peroxidation since the discovery of the essential fatty acids[J].Biochem Biophys Res Comm,2010,399(3):318-323.
[20]Guerranti R,Pagani R,Neri S,et al.Inhibition and regulation of rat liver L-threonine dehydrogenase by different fatty acids and their derivatives[J].Biochim Et Biophys Acta Gen Subj,2001,1568(1):45-52.
[21]Sugino T,Shirai T,Kajimoto Y,et al.l-Ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism[J].Nutr Res,2008,28(11):738-743.
[22]段怡譞.菊粉影响肥胖发生发展的代谢组学研究[D].武汉:华中科技大学,2013.
[23]Rebouche C H.Carnitine metabolism and its regulation in microorganisms and mammals[J].Ann Rev Nutr,1998,18(1):39-61.
[24]Kim I Y,Jung J,Jang M,et al.1H NMR-based metabolomic study on resistance to diet-induced obesity in AHNAK knock-out mice[J].Biochem Biophys Res Comm,2010,403(3):428-434.
[25]Holmes E,Li J V,Athanasiou T,et al.Understanding the role of gut microbiome-host metabolic signal disruption in health and disease[J].Trends Microbiol,2011,19(7):349-359.
[26]Jung J,Kim I Y,Kim Y N,et al.1H NMR-based metabolite profiling of diet-induced obesity in a mouse mode[J].Bmb Rep,2012,45(7):419-424.
[27]Sun Y,Zhang G,Hawkes C A,et al.Synthesis of scyllo-inositol derivatives and their effects on amyloid beta peptide aggregation[J].Bioorg Med Chem,2008,16(15):7177-7184.
[28]李贵海,孙敬勇,张希林,等.山楂降血脂有效成分的实验研究[J].中草药,2002,33(1):52-54.
[29]张良,姜思凡,万军,等.炮制对山楂主要化学成分的影响[J].长春中医药大学学报,2014,30(1):31-34.