Anti-Hyperlipidemic Effect And Potential Mechanisms Of Caffeoylquinic Acids Isolated From Pandanus Tectorius

The fruit of Pandanus tectorius(PTF)has a long history of use as a folk medicine to treat hyperlipidemia in Hainan province,South China.Our previous studies have shown that the n-butanol extract of PTF have an adequate therapeutic effect on dyslipidemic animals induced by high-fat diet,and the caffeoylquinic acids were identified as the main lipid-lowering active ingredients.In this thesis,seven caffeoylquinic acids isolated from PTF were screened for the lipid-lowering activity.The potential mechanism of their hypolipidemic effect was also explored.The caffeoylquinic acids from PTF were first screened for the lipid-lowering activity in HepG2 cells elicited by oleic acid.An MTT assay was used to evaluate the cytotoxicity of each compound.Spectrophotometry after Oil-Red O staining and microscopic observation were combined to analyzed the inhibitive effect of active components identified above on oleic acid-elicited lipid accumulation in HepG2 cells.The intracellular levels of triglyceride(TG)and total cholesterol(TC)were also quantified by specific kits.The mRNA levels of several key lipid metabolic genes in HepG2 cells were determined by real-time quantitative polymerase chain reaction(RT-PCR)in order to explore the potential mechanism of caffeoylquinic acids-mediated hypolipidemic actions.The results showed that:(1)Three caffeoylquinic acids in Pandanus tectorius fruit,i.e.chlorogenic acid,isochlorogenic acid A and 3,4,5-tri-O-caffeoyl quinic acid,significantly inhibit lipid accumulation induced by oleic acid in HepG2 cells;(2)These three caffeoylquinic acids showed no significant cytotoxicity at concentrations of 1-10?mol·L-1 as determined by MTT assay;(3)Chlorogenic acid,isochlorogenic acid A and 3,4,5-tri-O-caffeoyl quinic acid decreased lipid accumulation and TG content in a dose-dependent manner,while chlorogenic acid significantly reduce the intracellular TC as well.These three caffeoylquinic acids may therefore play a major role in the lipid-lowering effect of Pandanus tector·us fruit;(4)As quantified by real-time PCR,chlorogenic acid and isochlorogenic acid A can significantly increased lipid oxidation-related genes PPAR-a,CPT-1,and ACOX 1 while chlorogenic acid,isochlorogenic acid A and 3,4,5-tri-O-caffcoyl quinic acid significantly decreased lipogcnic genes SREBP-1c,SREBP-2,HMGR,ACC,FAS.In summary,chlorogenic acid,isochlorogenic acid A and 3,4,5-tri-O-caffcoyl quinic acid isolated from Pandanus tecrorius fruit possess significant lipid-lowering activities.Their hpolipidemic activity may be mediated by up-regulating the expression of lipid oxidative genes and down-regulating the expression of lipogenic genes.