Regulatory Effects Of Phenolic Acids And Esters In Propolis On Lipid Metabolism Disorders

Propolis is a natural product collected from plant tissues by Apis mellifera and rich in polyphenols.These substances provide a diversity of biological activities and pharmacological functions of propolis.In recent years,propolis has been found to have significant biological activities such as antioxidant,anti-inflammatory,anti-microbial,anti-tumor,anti-diabetic,lipid metabolism and immune regulation.Obesity,diabetes,cardiovascular and cerebrovascular diseases induced by lipid metabolism disorders have focused a high-profile attention.A large number of studies have found that natural products are effective sources of disease control and prevention.Previous experiments have shown that propolis extracts and some of these ingredients such as galangin,quercetin,p-coumaric acid and phenylethyl phenate could regulate fat metabolism disorders.Other few compounds,especially phenolic acids and phenolic esters in propolis have been reported to participate in the regulation.Therefore,the purpose of this paper is to evaluate the regulatory effects of the the main phenolic and phenolic esters in Chinese propolis on lipid metabolism disorders,clarifying the effective components and exploring the mechanism of actions.In this paper,eight phenolic acids(caffeic acid,p-coumaric acid,ferulic acid,iso-ferulic acid,3,4-dimethoxycinnamic acid,cinnamic acid,4-methoxycinnamic acid and cinnamylideneacetic acid),eight phenolic esters(caffeic acid phenethyl ester,caffeic acid cinnamyl ester,caffeic acid benzyl ester,p-coumarin acid cinnamyl ester,p-coumarin acid benzyl ester,ferulic acid benzyl ester,cinnamic acid cinnamyl ester and 4-methoxycinnamic acid cinnamyl ester)and 3,4-dihydroxybenzaldehyde in Chinese propolis were studied.MTT assay was used to detect cell viabilities of these components in human hepatocyte L02 and mouse preadipocyte 3T3-L1.The proper concentrations of drug therapy were determined.The L02 hepatocyte lipid accumulation model was established,and the optimal compounds of the phenolic acids and phenolic esters in the propolis were screened by oil red O staining method.Then,the optimal composition was selected to analyze the protein expression levels of endoplasmic reticulum stress pathway and peroxisome proliferator-activatived receptors(PPARs).Finally,3T3-L1 adipocytes were treated with palmitic acid and 17 polyphenols components to dectedct palmitic acid-induced abnormal secretion of adipokines and inflammatory factors.P-coumaric acid,iso-ferulic acid,3,4-dihydroxybenzaldehyde,p-coumaric acid benzyl ester,p-coumaric acid cinnamic ester,caffeic acid benzyl ester,caffeic acid benzyl ester and caffeic acid cinnamic acid ester can effectively reduce free fatty acid-induced L02 cell lipid accumulation.Among them,caffeic acid cinnamic acid ester is the only compound that had a significant lipid-lowering effect at all the four concentrations(5,10,50 and 100 ?mol/L)with a relatively high content in propolis and rarely mentioned in previous researches.In further research,the expression levels of ER sress pathway and PPARs protein in L02 cells were detected by Western blotting.Caffeic acid cinnamic acid ester was able to effectively reduce the expression of CHOP and ATF-6 in ER stress up-regulation.The upregulation of PPAR-alpha and down-regulation of PPAR-? were also induced by caffeic acid cinnamic acid ester,which had indeed improved intracellular lipid metabolism disorders in L02 cells.The multi-factor detection kit was used to detect the expression of seven cytokines serected by adipocytes after treated with palmitic acid and 17 compounds in propolis.The seven cytokines included adiponectin,leptin,resistin,interleukin 6,tumor necrosis factor-?,monocyte chemoattractant protein-1 and plasminogen activator inhibitor.17 phenolic compounds in propolis can regulate fat factor secretion abnormalities to different degrees.Every single compound had a different regulatory profile of the seven cytokines.17 phenolic acids and phenolic esters in propolis can regulate the two types of lipid metabolism disorders.The research work clarified the targets of regulation and provided a preliminary experimental basis for the further study of propolis in the treatment of related diseases...